Manuel Sartori

Suprasegmental Criteria in Medieval Arabic Grammar *

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Introduction

"What's the difference between badal and ʿaṭf bayān?". 1 Here is a student's question, quite legitimate, but which, interestingly enough, does not have an immediate answer, which seems to signal its "problematic" nature. The crux of the problem lies, in short, in how to tell them apart and account for the differences between ʿaṭf bayān on the one hand and badal on the other hand. So let's pose the problem as it stands to the attentive reader: what is the difference between muḥammad of al-ṣalātu wa-l-salāmu ʿalā nabiyyihi muḥammadin and ʿumar of ʾaqsama bi-l-llāhi ʾabū ḥafṣin ʿumar (< ʿumaru 2 ), the first being categorized by Arabic grammar as badal and the second as ʿaṭf bayān? What are the criteria for distinguishing what seems to be exactly the same, as will be shown in the following two examples borrowed from Ibn Ǧinnī (d. 392/1002) in his Lumaʿ fī al-ʿarabiyya:

( In the rest of this article I will keep the terms badal (permutative), mubdal minhu (that for which the badal is substituted), ʿaṭf al-bayān (explanatory apposition), but sometimes also those of ṣifa (qualification), naʿt (adjective) and tawkīd (corroboration) in transcription to simplify the translation. I will also keep the translation of the examples. 2

The pausal form is here necessitated by rhyme since it is a raǧaz by ʾAbū al-Ǧaḥḥāf Ruʾba b. ʿAbd al-ʿAǧǧāǧ b. Ruʾba al-Tamīmī al-Saʿdī (d. 145/762).

I say: so far, no obvious difference has appeared to me between the badal of the whole for the whole and the ʿaṭf al-bayān, and I believe that ʿaṭf albayān is nothing but badal, as this is obvious in Sībawayhi's remark, since he does not mention the ʿaṭf al-bayān, but says: "as to substituting the definite expression for the indefinite expression, like marartu bi-raǧulin ʿabdi l-llāhi 'I passed by a man ʿAbd Allāh', it is as if someone has asked: bi-man mararta 'by whom did you pass?' or that [the speaker] has imagined that it was said to him and that consequently, he puts in its place what is more defined than it [the indefinite expression]". (ʾaqūlu wa-ʾanā ʾilā al-ʾāna lam yaẓhar lī farq ǧalī bayn badal al-kull min al-kull wa-bayn ʿaṭf al-bayān bal lā ʾarā ʿaṭf al-bayān ʾillā al-badal ka-mā huwa ẓāhir kalām Sībawayhi fa-ʾinnahu lam yaḏkur ʿaṭf al-bayān bal qāla "ʾammā badal al-maʿrifa min al-nakira fa-naḥwa "marartu bi-raǧulin ʿabdi l-llāhi" ka-ʾannahu qīla "bi-man mararta" ʾaw ẓanna ʾannahu yuqālu lahu ḏālika fa-ʾabdala makānahu mā huwa ʾaʿraf minhu", ʾAstarābāḏī ŠK II, 397; Sībawayhi Kitāb II, 12 and Sībawayhi Kitāb(3) II, 14, hāḏā bāb badal al-maʿrifa min al-nakira wa-l-maʿrifa min al-maʿrifa)

The fact that even such a distinguished grammarian and logician as ʾAstarābāḏī was confused by the problem suggests that it was unusually difficult, and indeed we find similar confusion in the works of other Arab grammarians. As we shall show, some of them reduce this difference to merely inflectional or, at best, pragmatic criteria, while others invoke an entirely different criterion, one which is more hinted at than explicitly stated. The latter approach has been largely overlooked in Western treatments of the phenomenon, which rely heavily on the traditional formal analysis, thereby increasing the need to rescue it from neglect.

1

The Traditional Approach

1.1

The Reasons for This Embarrassment Let us recall briefly that the two types under study, badal and ʿaṭf bayān, belong to the generic category known as tawābiʿ that is to say to the class of appositives. In the terms of traditional Arabic grammar, these appositives are five in number: ṣifa (or naʿt), adjectival qualification; taʾkīd (or tawkīd), corroboration; badal, permutation; ʿaṭf bayān, explanatory apposition; and ʿaṭf nasaq, coordination (cf. Ġalāyīnī Ǧāmiʿ III,. Even if the last of these, unlike the first four, is not a juxtaposition, we can distinguish in each of them at least a categorized term as tābiʿ, that is to say an appositive, and preceding it, its matbūʿ, that is to say the term which is followed by the appositive, the tābiʿ following (generally) in declension its matbūʿ.

If the ʿaṭf al-bayān does not have subdivisions, the same is not true for the badal as stated by ʾAstarābāḏī in the quote above. The badal is subdivided into four types, 3 respectively badal al-kull min al-kull (substitution of the whole for the whole); badal al-baʿḍ min al-kull (substitution of the part for the whole); badal al-ištimāl (inclusive substitution); al-badal al-mubāyin (the contradictory substitution), itself subdivided into three sub-types which are badal al-ġalaṭ (substitution of error), badal al-nisyān (substitution of oversight) and badal al-ʾiḍrāb (substitution of retractation, cf. Ġalāyīnī Ǧāmiʿ III, 179-180 and Yaʿqūb 2006: IV, 88). 4 According to Talmon, the ʿaṭf al-bayān would be a syntactic innovation (maybe we should rather say conceptual) which was introduced by Sībawayhi (d. 180/796?), who granted it a degree of autonomy approaching that of a ṣifa (cf. Talmon 1981: 279). According to an Arab grammarian, Ibn Barhān al-ʿUkbarī (d. 456/1064), the ʿaṭf al-bayān actually seems to be problematic since he writes in his Šarḥ al-Lumaʿ: Know, concerning the ʿaṭf al-bayān, that few grammarians know it, that Sībawayhi mentioned it only incidentally in some sections […], and that he has not reserved for it any chapter. (wa-ʿlam ʾanna ʿaṭf al-bayān lā yaʿrifuhu 5 kaṯīr min al-naḥwiyyīn wa-ʾinna-mā ḏakarahu Sībawayhi ʿāriḍan fī mawāḍiʿ […] wa-lam yufrid lahu bāban, Ibn Barhān al-ʿUkbarī ŠL I, 236) A later grammarian, Baṭalyawsī (d. 521/1127), even points out the three features of ʿaṭf al-bayān which account for its "strangeness among grammarians" The translations given here to these terms are that of Carter (cf. Širbīnī Nūr 474). I will only note that for ʾAstarābāḏī al-badal al-mubāyin is, in fact, al-badal al-ġalaṭ and that under this latter, he distinguishes, in the order stated here, the types of ġalaṭ ṣarīḥ muḥaqqaq (substitution of a real error) then of ġalaṭ nisyān (substitution of oversight) and then finally of ġalaṭ badāʾ (substitution of second thought) (cf. ʾAstarābāḏī ŠK II, 403-404). On his side, Wright reduces to two the sub-types of the badal al-ġalaṭ, subsuming badal al-ʾiḍrāb (the permutative of retractation) with badal al-badāʾ (the substitution of a new opinion, something one would like to substitute for the original statement), and subsuming under only one category badal al-ġalaṭ wa-l-nisyān (the permutative of error and forgetfulness, cf. Wright 1996:II, 286). 5

The text gives yāʾ-hāʾ-rāʾ-fāʾ that could be read yahrifu "to praise excessively" (cf. [START_REF] Wehr | Arabic-English Dictionary[END_REF]Wehr :1026a)), but which does not make sense here. It is presumably a typo, hāʾ and ʿayn being side by side on a keyboard.

(ġarābatihā ʿinda al-naḥwiyyīna, Baṭalyawsī Rasāʾil 206): the vocative (nidāʾ), the vague terms (mubhamāt), that is to say the demonstratives (ʾasmāʾ al-ʾišāra), and the active participle (ism al-fāʿil). 6 By cross-reading the presentations made by traditional Arab grammars, the ʿaṭf al-bayān represents, in fact, an intersection between ṣifa and badal, with which it shares some characteristics, but from which it is distinguished by others. This is why a grammarian like Baṭalyawsī devotes a study, in his Rasāʾil, to the difference between naʿt, ʿaṭf bayān and badal . As such, one of the best presentations, although not free from controversy, of the ʿaṭf al-bayān between ṣifa and badal is that of Ibn Yaʿīš (d. 643/1245) in his commentary on Zamaḫšarī's Mufaṣṣal (d. 538/1144, cf. Ibn Yaʿīš ŠM II, 272-274).

However, none of the grammarians (ancient or modern) clearly explains the distinction that can be made between badal and ʿaṭf bayān, which may help us to understand the circumspection of ʾAstarābāḏī in the matter. What is important to bear in mind at this stage is that among the four types of badal, the ʿaṭf al-bayān would be confused with the badal of the whole for the whole. It is at least what grammarians say when they indicate that this equivalence is true under two conditions (yaqūlu al-nuḥāt ʾinna kull mā ṣaluḥa ʾan yakūna ʿaṭf bayān ǧāza ʾan yakūna badalan bi-šarṭayn, [START_REF] Yaʿqūb | Mawsūʿat ʿulūm al-luġa al-ʿarabiyya[END_REF]: VI, 422, cf. also Howell 1880: I, 481). 7 What should also be kept in mind is that the ʿaṭf al-bayān, representing an intersection between badal and ṣifa, obviously poses problems for grammarians to define it precisely. As Esseesy says about the appositives, "the syntactic and semantic boundaries among these subclasses were not always drawn sharply […], leading to instances where syntactic ambiguity becomes inevitable, as in ḍarabtu ʾabā ʿabdillāhi zaydan 'I hit ʾAbū ʿAbdallāh, Zayd', which is bound to be construed either as ʿaṭf bayān 'explicative coordinating' or as badal" (Esseesy 2006: 124-125). Owens specifies indeed that "apparently grammarians found it difficult to define it clearly" (Owens 1990: 59).

However, there remains a question which should not be left unanswered, especially since some grammarians, as we will see, provide an implicit solution that must be made explicit: how to distinguish between (1) and ( 2) above? 6

These considerations being once again only inflectional, and therefore more than suspicious in a language where the inflection by means of short vowels is not marked (cf. below, fn. 9), I will not deal with it here. 7

The two conditions in question here are that 1. the tābiʿ can take the place of the matbūʿ and thus that the operator on the matbūʿ can apply to the tābiʿ and 2. that no semantic impossibility results from the commutation of the two. The first of the two belongs precisely to the pragmatic criteria discussed by the grammarians (cf. below).

While Western Arabists do occasionally provide a explanation, albeit rarely, 8 our goal must be to focus on the view of the Arab grammarians, since we are here dealing with the Foundations of Arab Linguistics.

1.2

Traditional Criteria of Distinction between ʿaṭf bayān and badal Let us first sum up very briefly the traditional criteria applied by the Arab grammarians to distinguish between ʿaṭf bayān and badal.

As for the differences between the two, the fact is that, when consulting ancient grammarians, there are at least two criteria of distinction between badal and ʿaṭf bayān, those criteria being widespread among ancient grammarians. The first one pertains to the linguistic belief in a consistent ʾiʿrāb, the difference made between the two from Mubarrad onwards being linked to inflection within the framework of the vocative, since he says that the badal is inflected in the nominative while the ʿaṭf al-bayān is to the accusative (cf. Mubarrad Muqtaḍab IV, 468 and 475). That is also what Ibn al-Sarrāǧ (d. 316/929) clearly states:

The difference between the ʿaṭf al-bayān and the badal is that the implicit value (taqdīr) of the ʿaṭf al-bayān is that of the appositive adjective of the first noun while the implicit value of the badal is to replace the first [term], and you say in the framework of the vocative when you want to use the ʿaṭf al-bayān: yā ʾaḫānā zaydan by putting on the accusative with tanwīn since it is not the vocative element, and if you wish to use the badal you say: yā ʾaḫānā zaydu. (wa-l-farq bayn ʿaṭf al-bayān wa-l-badal ʾanna ʿaṭf al-bayān taqdīruhu al-naʿt al-tābiʿ li-l-ism al-ʾawwal wa-l-badal taqdīruhu ʾan yūḍaʿa mawḍiʿ al-ʾawwal wa-taqūlu fī al-nidāʾ ʾiḏā ʾaradta ʿaṭf al-bayān "yā ʾaḫānā zaydan" fa-tanṣubu wa-tunawwinu li-ʾannahu ġayr munādā fa-ʾin ʾaradta al-badal qulta "yā ʾaḫānā zaydu", Ibn al-Sarrāǧ ʾUṣūl I, 432) 9

Ibn al-Dahhān al-Baġdādī (d. 569/1174) sums this up very briefly in his comment on ʿaṭf al-bayān: "it is recognized within the vocative explicitly and 8

This is particularly the case of Larcher who indicates, following the Arab grammarians, that the badal represents the essential term compared to the mubdal minhu which is the accessory one (cf. Larcher 2017:35). For the details of the treatment of the badal and the ʿaṭf al-bayān by the Arabists, cf. Sartori 2018a:552-558. 9

He also speaks about it in the context of the vocative (nidāʾ, cf. Ibn al-Sarrāǧ ʾUṣūl I, [300][301][302][327][328]cf. also II,[78][79]II,116;II,[134][135]. Ibn al-Sarrāǧ indicates that the categories of badal and ʿaṭf bayān are the terminologies of the so-called grammarians of Basra (cf. Ibn al-Sarrāǧ ʾUṣūl I, 328).

elsewhere implicitly" (yuʿrafu fī al-nidāʾ lafẓan wa-fī ġayrihi taqdīran, Ibn al-Dahhān al-Baġdādī Šarḥ 544). However, these inflections do not appear in written Arabic with its scriptio defectiva, nor is inflection prominent in conventional pronunciation, where pausal forms predominate. 10 The appeal to inflection which is commonly made by the grammarians therefore has little explanatory value.

The second criterion raised by the grammarians is, in fact, twofold, invoking two pragmatic features which are discussed by Arab grammarians of all periods. The first concerns the badal and is linked to the speaker's intention: on him depends the fact that the badal, because being in a relation of stricto sensu referential uniqueness with its mubdal minhu, is conceived as the essential term while the term to which it is apposed is only as an accessory one; the second concerns the ʿaṭf al-bayān and again points to the speaker's intention: on him depends the restriction of the extension of the term to which the ʿaṭf al-bayān is apposed and, correlatively, the precision of its intension. 11 The ʿaṭf al-bayān is then not an essential term, but rather, as with adjectival qualification generally, only an accessory term and, like it, is not in a relation of strictly referential uniqueness with the term to which it is apposed 12 , unlike the badal.

However, there are grammarians whose enquiries go beyond these two criteria, challenging and extending both the distributional/inflectional and the semantic/pragmatic approach. As I shall show below, they introduce another criterion, this time of suprasegmental nature, arising from the fusion of the pragmatic and the syntactic approach… 10

The pausal form is the default ending both in mediaeval and contemporary Classical Arabic, to which we may add that the full inflectional system of three cases is not found with every class of word-many have only two inflections, and others are invariable (e.g. mūsā, ʿīsā), or the inflections may be masked by suffixes (e.g. kitābī) or obscured by orthographical ambiguities. Even Qurʾānic Arabic can be seen to be "without desinential inflection, and that this syntactically irrelevant inflection was introduced for prosodic reasons, linked to the changing recitation of the Qurʾān (taǧwīd)" (Larcher 202137:). In effect, overt inflection is the exception (only in the case of the "six nouns", cf. Sartori 2010 and Sartori 2018b:69) rather than the rule, and for a language known for inflection, this reduces to very few cases where it is actually performed! 11 "Intension" and "extension" are borrowed from Logic: "l'extension d'un terme est l'ensemble des référents qu'un terme est susceptibe de dénoter en langue […]. L'intension (ou, plus traditionnellement, la compréhension) d'un terme correspond aux aspects pertinents de son contenu notionnel qui conditionnent ses emplois référentiels et qui rendent compte de ses relations avec les autres termes de la langue" (Riegel et al. 2004:179-180). 12 Suyūṭī (d. 911/1505) even states very clearly that "the explanatory apposition only exists after a multireferential [noun]" (ʿaṭf al-bayān lā yakūnu ʾillā baʿd muštarak, Suyūṭī ʾAšbāh III, 218).

A New Criterion of Suprasegmental Nature

The authors who follow do not abandon the presentation of badal as being the essential term and its mubdal minhu as the accessory one. Similarly, they still present the ʿaṭf al-bayān as a generally better-known element, clarifying the term to which it is associated, by restricting its extension. They even point to the inflectional criterion to distinguish between the two. However, those grammarians add something interesting that transcends the various branches of indegenous Arabic grammar and is therefore not specific to any one branch.

In this section we introduce a syntactic criterion, that of repetition, resumption, or independence (i.e. beginning a new sentence), this last having the morphological consequence that by starting a new sentence a pausal ending appears on the preceding element..

2.1

Repetition (takrīr, takrār or tašdīd)

2.1.1 Tašdīd I will begin with the most prevalent criterion among ancient grammarians, namely that of repetition which one finds in their works in the forms of takrīr, and more marginally takrār or tašdīd. It is with the latter that I will start this section since Ibn Ǧinnī begins by defining the badal as "following the course of the tawkīd in [factual] assertion and doubling" (al-badal yaǧrī maǧrā altawkīd fī al-taḥqīq wa-l-tašdīd, Ibn Ǧinnī Lumaʿ 144), which he is visibly the first to do so by using the term tašdīd. What needs to be understood here is actually twofold: badal and mubdal minhu being in a referential uniqueness relationship, it thus amounts to saying the same thing twice, both in intention and intension.

That is confirmed by Ibn al-Ḫabbāz (d. 637/1239), commentator of Ibn Ǧinnī's Lumaʿ. Like Ibn Ǧinnī before him, he indicates about the badal that it follows the course of the tawkīd in [factual] assertion and doubling (al-taḥqīq wa-l-tašdīd) and specifies the meaning of tašdīd:

It is because when you say qāma ʾaḫūka zaydun then the badal and the mubdal minhu are two expressions referring to a single meaning, so it is like you said qāma ʾaḫūka ʾaḫūka. (fa-li-ʾannaka ʾiḏā qulta qāma ʾaḫūka zaydun fa-l-badal wa-l-mubdal minhu ʿābiratāni ʿan maʿnā wāḥid fa-ka-ʾannaka qulta qāma ʾaḫūka ʾaḫūka, Ibn al-Ḫabbāz Tawǧīh 275) But this is also equivalent to repeating, qāma ʾaḫūka zaydun amounting to saying qāma ʾaḫūka qāma zaydun, which Bāqūlī (d. 543/1148) and Ibn al-Faḫḫār (d. 754/1353) will express very clearly (cf. below).

2.1.2

Takrīr As for ʿAbd al-Qāhir al-Ǧurǧānī (d. 471/1078), even though he does not expressly address the difference between ʿaṭf bayān and badal, he still has an interesting observation to make about the latter: Know that the badal virtually repeats the operator as it was before, so when you say marartu bi-qawmika ṯulṯayhim then ṯulṯayhim is in the genitive because of the preposition as if you had said bi-ṯulṯayhim […]. The badal virtually repeats the operator only because the mubdal minhu is neglected in favor of the badal […] and this is not the case with the ṣifa since when you say ǧāʾanī zaydun al-ẓarīfu then zayd is not virtually neglected, but rather both [terms] follow the course of the single noun. (iʿlam ʾanna al-badal fī ḥukm takrīr al-ʿāmil ka-mā taqaddama fa-ʾiḏā qulta "marartu bi-qawmika ṯulṯayhim" kāna ṯulṯayhim maǧrūran bi-ḥarf ǧarr ḥattā ka-ʾannaka qulta "bi-ṯulṯayhim" […] wa-ʾinna-mā kāna al-badal fī ḥukm takrīr al-ʿāmil li-ʾaǧl ʾanna al-badal yutraku ʾilayhi al-mubdal minhu […] wa-laysa ka-ḏālika al-ṣifa li-ʾannaka ʾiḏā qulta "ǧāʾanī zaydun al-ẓarīfu" lam yakun zaydun fī ḥukm al-matrūk bal kānā ǧāriyayni maǧrā ism wāḥid, Ǧurǧānī MŠĪ II, 929) What Ǧurǧānī adds in contrast to his predecessors is the takrīr element contained in the badal that, if we are to believe ʾUšmūnī (d. ca. 900/1495) used by Vernier (cf. Vernier 1891: II, 176), the grammarians of the so-called school of Kufa partly called takrīr. Compared with the takrīr, which visibly presupposes a pause, he presents the case of the adjective (which we know the ʿaṭf al-bayān is close to) which, on the contrary, implies a lack of pause, that is to say a link, which is implied by its comparison with the single noun (ism wāḥid).

Baṭalyawsī, in the section which he devotes to the difference between naʿt, badal and ʿaṭf bayān, specifies four of them, the third of which being: that one supposes with the badal a reiteration of the operator, as if it belonged to another sentence, whereas one does not suppose that with the ʿaṭf al-bayān which is on the contrary in this respect like the adjective.

(ʾanna al-badal […] yuqaddaru maʿahu ʾiʿādat al-ʿāmil wa-ka-ʾannahu min ǧumla ʾuḫrā wa-ʿaṭf al-bayān lā yuqaddaru fīhi ḏālika bal huwa fī hāḏā alwaǧh ka-l-naʿt, Baṭalyawsī Rasāʾil 204)

Thus Baṭalyawsī indicates both the element of repetition contained in the badal and, as a result, that the latter is then "as if it belonged to another sentence". By this reference to "another sentence", this author then indicates very clearly that the badal is preceded by a pause, which will be later on confirmed by Ibn Barhān al-ʿUkbarī (cf. below) who replaces ǧumla with his own term kalām "utterance". 13 Despite what has been said, especially by Talmon, noting that Zamaḫšarī, like others, was only going by a pragmatic feature (the speaker's premeditation, cf. Talmon 1981: 291), ʾAbū al-Qāsim still devotes a section to the independence of the badal, an independence which he links to the concept of repetition when he says:

And what indicates its independent character is that it may be judged as having its operator repeated. (wa-l-laḏī yadullu ʿalā kawnihi mustaqillan ʾannahu fī ḥukm takrīr al-ʿāmil, Zamaḫšarī Mufaṣṣal 155) This independent character (mustaqill) of the badal is thus seen to be closely related to repetition, and therefore implying the existence of a pause that precedes it.

Bāqūlī, known as Ǧāmiʿ al-ʿulūm, specifies the same thing speaking also of "repetition". He does it a first time for the badal, for which he says that the operator is repeated and that, implicitly, the badal belongs to another sentence (li-ʾanna al-ʿāmil mukarrar fī al-badal wa-l-badal fī al-taqdīr min ǧumla ʾuḫrā, Ǧāmiʿ al-ʿulūm Kitāb šarḥ al-Lumaʿ fī al-naḥw 256). He gives for it as an example zaydun ḏahaba ʿamrun ʾaḫūhu that he paraphrases zaydun ḏahaba ʿamrun ḏahaba ʾaḫūhu (cf. Ǧāmiʿ al-ʿulūm Kitāb šarḥ al-Lumaʿ fī al-naḥw 257).

He once again addresses this aspect of repetition at the level of the ʿaṭf albayān, clearly indicating that, unlike the badal, no such repetition is found with ʿaṭf al-bayān:

The ʿaṭf al-bayān resembles the ṣifa in that it is an appositive of the first [term] and that it clarifies it, except that it is not derived from the verb, unlike the ṣifa. It resembles the badal in its form, except that it differs from it because the badal is implicitly in the repetition of the operator, and that is unlike it [ʿaṭf al-bayān]. This is manifest in the chapter of the vocative: when you say yā ʾaḫānā zaydan "o our brother Zayd!", if you treat zayd as a ʿaṭf bayān, you put the accusative since you make it replace ʾaḫānā, and if you treat it as a badal, you suppose a repetition of yā and you say yā ʾaḫānā zaydu "o our brother, Zayd!", as if you said [yā ʾaḫānā] yā zaydu. (ʿaṭf al-bayān yušbihu al-ṣifa fī kawnihi tabʿan li-l-ʾawwal wa-

13

The sentences can indeed be segmented but also linked (or bound) (cf. below fn. 17) as is the case in subordinated constructions such as yurīdu ʾan yatakallama "he wants to speak" whereas the linguistic kalām (which one can render by 'utterance' or 'speech') "is bounded by silence" (Carter 2017:151 Goguyer 1887: 342ff. for the ʿaṭf al-bayān and 358-361 for the badal). He even addresses the difference between the two (cf. Goguyer 1887: 344-346). He expressly takes into account only pragmatic and semantic aspects, but still specifies:

De tout nom dont on peut dire qu'il est adjoint expositif, servant à élucider ou particulariser, on peut dire aussi qu'il est permutatif de tout en tout, servant à fixer et corroborer le sens, parce qu'il se trouve en effet comme si le régissant était répété pour lui. À cette règle les uns font une exception, les autres deux, d'autres même davantage, mais toutes se trouvent comprises dans l'expression que j'ai employée : « s'il n'est pas impossible de lui faire remplacer son antécédent. » (Goguyer 1887: 345) Further on takrīr, cf. also ʾUšmūnī and Ḫuḍarī (d. 1287/1870) (ʾUšmūnī Manhaǧ II, 435 and Ḫuḍarī Ḥāšiya II, 159).

2.1.3

Takrār Ibn ʿUṣfūr, but this time in his Muqarrib, deals again with the two types of appositives (cf. Ibn ʿUṣfūr Muqarrib 321-326 for the badal and 327-328 for the ʿaṭf al-bayān), and, in the section devoted to the latter, he explains the difference between ʿaṭf bayān and badal, by expressly connecting it with the criterion of takrār al-ʿāmil (repetition of the operator):

The difference between it [ʿaṭf al-bayān] and the badal is that you do not intend to reject the first [term] with the ʿaṭf al-bayān as you do with the badal […] because the purpose of the badal is to repeat the operator […] and that is not allowed in the case of the ʿaṭf al-bayān because no repetition is intended here.

(wa-l-farq baynahu [ʿaṭf al-bayān] wa-bayn albadal ʾannaka lā tanwī bi-l-ʾawwal al-ṭarḥ fī ʿaṭf al-bayān ka-mā tafʿalu fī al-badal […] li-ʾanna al-badal fī niyyat takrār al-ʿāmil […] wa-ḏālika lā yaǧūzu [fī] ʿaṭf al-bayān li-ʾannahu laysa fī niyyat takrār al-ʿāmil, Ibn ʿUṣfūr Muqarrib 327)

We find this use of takrār instead of takrīr among others in Ibn al-Faḫḫār, commentator of Zaǧǧāǧī's Ǧumal (d. 337/949), who, although he sets out the five kinds of appositives, does not deal with the ʿaṭf al-bayān (cf. Ibn al-Faḫḫār ŠǦ and Ibn al-Faḫḫār ŠǦ( 2)). As for the badal, he immediately indicates in the definition the aspect of repetition:

The badal is the appositive whose implicit value is the repetition of the operator, so, when you say qāma zaydun ʾaḫūka it has the implicit value of qāma zaydun qāma ʾaḫūka. (al-badal huwa al-tābiʿ ʿalā taqdīr takrār al-ʿāmil fa-ʾiḏā qulta "qāma zaydun ʾaḫūka" fa-ʾinnahu fī taqdīr "qāma zaydun qāma ʾaḫūka", Ibn al-Faḫḫār ŠǦ I, 190) Ibn ʿAqīl finally (d. 769/1367) states that substitution (badal) occurs in the intention of repeating the operator (al-badal ʿalā niyyat takrār al-ʿāmil, Ibn ʿAqīl ŠA II, 59).

One last element to note is that this dimension is not totally ignored among Arabists. Wright, for example, for whom ʿaṭf bayān can be regarded as functionnong in a similar way to the adjectival qualifier, ṣifa, "This apposition is equivalent to the use of wa-huwa, wa-hiya, etc. (e.g. ǧāʾanī ʾaḫūka wa-huwa zaydun)" [START_REF] Wright | A Grammar of the Arabic Language[END_REF]: II, 287), which is basically approaching the solution by making of it a link of concomitant nature to be distinguished from the badal where there is a recommencing and therefore a break.

2.2

Resumption (istiʾnāf) and Independence (istiqlāl) Regarding the distinction between badal and ʿaṭf bayān, the other distinguishing criterion that one can identify from reading the ancient grammarians, though it is less prominent than takrīr, is that of istiʾnāf, that is to say resumption 14 as well as that of istiqlāl, that is to say independence.

I will start with Ibn Ǧinnī, who, when he writes about the ʿaṭf al-bayān "You say qāma ʾaḫūka muḥammadun as you say qāma ʾaḫūka al-ẓarīfu" (taqūlu "qāma ʾaḫūka muḥammadun" ka-qawlika "qāma ʾaḫūka al-ẓarīfu", Ibn Ǧinnī Lumaʿ 148), significantly chooses the formulation ka-qawlika "as if you were sayning". Could this be the trace of the fact that the apposed element and its ʿaṭf bayān must be pronounced as one does in the case of a mawṣūf and its ṣifa, that is to say in one breath, as a single noun (ism wāḥid, cf. ʿAbd al-Qāhir al-Ǧurǧānī above)? Such an idea cannot be ruled out, in view of the importance of the word as here, 15 especially in the light of what follows.

The first among the grammarians to be perfectly explicit on this subject is, it seems, Ibn Barhān al-ʿUkbarī who precisely links takrīr and istiʾnāf. About the badal he says indeed immediately this: "the badal is one of the appositives except that it has originally the implicit value of two sentences: when you say ḍarabtu zaydan raʾsahu the base is ḍarabtu zaydan ḍarabtu raʾsahu" (al-badal ʾaḥad al-tawābiʿ ʾillā ʾannahu fī taqdīr ǧumlatayn fī al-ʾaṣl ʾiḏā qulta "ḍarabtu Ibn Barhān al-ʿUkbarī could not be clearer, his recourse to muttaṣil on the one hand, to mustaʾnaf and munqaṭiʿ on the other hand, the first referring to ʿaṭf albayān and the second to badal, leaving no doubt about his concept of the difference between these two types of appositions: in addition to the traditional criteria already mentioned, 17 he adds one, suprasegmental in nature, which takes into account pronunciation in juncture or segmentation! 18 This confirms, in my opinion, the reading of Ibn Ǧinnī's as, that is to say that an ism and its ṣifa are said in one breath. This criterion of resumption, in the express form of istiʾnāf, is then found in particular in Ibn ʿUṣfūr who, in the section devoted to the badal, writes: "the badal is in the intention of a resumption of an operator, and when you say 16

That is, with the intention of saying zayd. 17

Note that he does not reject the traditional views, and nothing prevents him from contrasting the two structures purely in terms of their inflection: "yā hāḏā zaydun do you not see that the tanwīn of zaydun indicates that it is not a badal and against that you say yā ʾayyuhā al-raǧulu zaydu where zaydu is a badal of ʾayy and for that is indeclinable in u without bearing any tanwīn?" (yā hāḏā zaydun ʾa-lā tarā ʾanna tanwīn zaydun qad dalla ʿalā ʾannahu laysa bi-badal wa-ʿalā hāḏā taqūlu yā ʾayyuhā al-raǧulu zaydu fa-zaydu […] yakūnu badalan min ʾayyu fa-li-ḏālika kāna mabniyyan ʿalā al-ḍamm ġayr munawwan, Ibn Barhān al-ʿUkbarī ŠL I, 236). 18

This distinction is taken from the Swiss linguist Charles Bally (1865-1947) (cf. Bally 1965) and, for grammar and linguistics of Arabic, from Larcher (cf. especially Larcher 2008 and[START_REF] Larcher | Syntaxe de l'arabe classique[END_REF].

qāma zaydun ʾaḫūka the implicit value is that of qāma ʾaḫūka" (al-badal fī niyyat istiʾnāf ʿāmil fa-ʾiḏā qulta "qāma zaydun ʾaḫūka" fa-l-taqdīr "qāma ʾaḫūka", Ibn ʿUṣfūr Muqarrib 321). What must be understood here, as elsewhere, is thus that qāma zaydun ʾaḫūka is equivalent to qāma zaydun qāma ʾaḫūka (cf. above, Bāqūlī and Ibn al-Faḫḫār). This element of resumption (istiʾnāf), linked to that of repetition (takrīr), implies the recognition of a pause, exemplified by the existence of "two sentences", which Ibn al-Dahhān al-Baġdādī expresses very well when, as before him Bāqūlī, he clearly indicates that badal and ʿaṭf bayān contrast with each other in the feature of repetition, where again the "two sentences" are mentioned:

Know that the badal and the element to which it is apposed are implicitly in two sentences, which is not the case of the qualifier and the qualified element (ṣifa and mawṣūf), nor of the corroborative and the corroborated element, nor of the ʿaṭf al-bayān and what precedes it. What confirms this to you is that the operator on the second element appears overtly in the words of the Almighty qāla l-malaʾu l-laḏīna -stakbarū min qawmihi li-llaḏīna -stuḍʿifū li-man ʾāmana minhum (Q. 7/75) "Said the Council of those of his people who waxed proud to those that were abased, to those of them who believed" (Arberry 1955: 180). 19 The overt expression of the lām indicates the correctness of our position. (iʿlam ʾanna al-badal wa-lmubdal minhu fī taqdīr ǧumlatayn wa-laysa al-ṣifa wa-l-mawṣūf wa-l-taʾkīd wa-l-muʾakkad wa-ʿaṭf al-bayān wa-mā qablahu ka-ḏālika wa-yuʾakkidu ḏālika ʿindaka ʾanna ʾiẓhār al-ʿāmil fī al-ṯānī qad ǧāʾa fī qawlihi taʿālā "qāla l-malaʾu l-laḏīna -stakbarū min qawmihi li-l-laḏīna -stuḍʿifū liman ʾāmana minhum" fa-ʾiẓhār al-lām yadullu ʿalā ṣiḥḥat mā ḏahabnā ʾilayhi, Ibn al-Dahhān al-Baġdādī Ġurra II, 817) He then has a contrastive definition that is very interesting: Know that the purpose of the appositive is either to [syntactically] complete the antecedent or not. The one that does not complete the first is the element coordinated by a coordinating particle. The one that completes the first is either in the implicit value of two sentences or in that of a single sentence. The one that is in the implicit value of two sentences is the badal […] and the one that is in the implicit value of a single sentence is of two types […] the first is the tawkīd and the second 19 "The chiefs among his people who were puffed up with pride, said unto those who were esteemed weak, namely unto those who believed among them" (Sale 1877:124). We find here, once again through the mention of "two sentences" (badal), as opposed to "single sentence" (ʿaṭf bayān), the element of repetition, therefore of pause… This reference to "two sentences" is found later, explicitly in ʾUšmūnī who contrasts badal and ʿaṭf bayān according to eight criteria, the last could not be clearer: "[the ʿaṭf al-bayān] has not the implicit value of another sentence, unlike the badal" (ʾannahu laysa fī al-taqdīr min ǧumla ʾuḫrā bi-ḫilāf al-badal, ʾUšmūnī Manhaǧ II, 414). This resumption is then linked to the independence of the badal from the mubdal minhu, unlike the relationship of dependence that exists between the ʿaṭf al-bayān and its maʿṭūf. On these, I already indicated that they were obviously to be considered as a single noun (ism wāḥid, cf. above ʿAbd al-Qāhir al-Ǧurǧānī) and as muttaṣil (cf. above Ibn Barhān al-ʿUkbarī). As for the independent relationship, it is apparently Ibn Mālik (d. 672/1274) who speaks of it first. Indeed, he writes concerning the badal that it is "like an independent element" (ka-mustaqill, Ibn Mālik ŠKŠ I, 579). Elsewhere, he further specifies that the badal is "the independent appositive because of the virtual requirement of the operator" (al-tābiʿ al-mustaqill bi-muqtaḍā al-ʿāmil taqdīran, Ibn Mālik Tashīl 172), which he says also in his own commentary on this book (cf. Ibn Mālik ŠT III, 186-188 for the ʿaṭf al-bayān and III, 189-201 for the badal).

It is, however, Ibn ʿAqīl who seems to be the first to link the maṣdar istiqlāl to the badal, writing about ʿaṭf al-bayān that it is: "the non-derived appositive similar to the qualifier in clarifying its antecedent and in its lack of [syntactic] independence" (al-tābiʿ al-ǧāmid al-mušbih li-l-ṣifa fī ʾīḍāḥ matbūʿihi wa-ʿadam istiqlālihi, Ibn ʿAqīl ŠA II, 57) where he addresses both the aspect of restriction of the extension (through ʾīḍāḥ) and where the non-independence that the ʿaṭf al-bayān shares with the qualifier contrasts indeed with the badal which, in turn, is conceived as independent. 20 Finally, ʾAstarābāḏī, surprisingly, says he does not understand the difference between the total badal and the ʿaṭf al-bayān. This said, he, however, recognizes in the badal its resumptive quality, though without using the term,

20

A later author holds the same view (cf. Ḫuḍarī Ḥāšiya II, 159).

since he gives two examples going in this direction. The first is taken from the Qurʾān and shows the badal intervening after a fāṣila, that is to say in the verse following the one in which the mubdal minhu is located: wa-ʾinnaka la-tahdī ʾilā ṣirāṭin mustaqīmin / ṣirāṭi l-llāhi, Q. 42/52-53, "And thou, surely thou shalt guide unto a straight path -the path of God" (Arberry 1955: 198). 21 The second is equally clear: "marartu bi-qawmin ʿabdi l-llāhi wa-zaydin waḫālidin and the nominative is good, that is to say 'these are ʿAbd Allāh, Zayd and Ḫālid'" (marartu bi-qawmin ʿabdi l-llāhi wa-zaydin wa-ḫālidin wa-l-rafʿ ǧayyid ʾay hum ʿabdu l-llāhi wa-zaydun wa-ḫālidun, ʾAstarābāḏī ŠK II, 397). Thus ʾAstarābāḏī indicates here that the badal can follow the inflection of the mubdal minhu, but that it can also be in nominative by implying making a new start, which is neither more nor less than a resumption, which nowadays would be shown by the punctuation, as follows: "I went through a group of men: ʿAbd Allāh, Zayd and Ḫālid" where the colon serves to indicate a (strong) segmentation and therefore a pause.

3

Segmentation vs Juncture So we see that many medieval Arab grammarians, when it comes to dealing with the badal, address the issue of takrīr (marginally takrār or tašdīd), in connection with istiʾnāf and istiqlāl. The takrīr we are talking about is syntactic, non-morphological, and not unknown to Sībawayhi himself, since we find it twice in the Kitāb (Derenbourg's edition in I, 433 l. 11 and II, 152 l. 2, cf. Troupeau 1976: 182). More interestingly, one of the two occurrences of takrīr in the Kitāb is specifically related to the badal:

You say marartu bi-zaydin ibni ʿamrin when you do not make of al-ibn a qualification but you make of it a badal or a takrīr like ʾaǧmaʿīna. (wataqūlu "marartu bi-zaydin ibni ʿamrin" ʾiḏā lam taǧʿal "al-ibn" waṣfan walākinnaka taǧʿaluhu badalan ʾaw takrīran ka-ʾaǧmaʿīna, Sībawayhi Kitāb( 2) II, 152 l. 2 = Sībawayhi Kitāb III, 566)

In the same way, it is interesting to note that of the three mentions in the Kitāb of the verb istaʾnafa in a syntactical meaning (cf. Troupeau 1976: 35), one is once more directly related to our topic. Indeed, at the very place of the single occurrence of the term ʿaṭf al-bayān in his Kitāb, Sībawayhi presents something that will, with rare exceptions as we have seen, be forgotten over time, and this element is in fact of suprasegmental nature: it is neither more nor less than the taking into account of a pause, marked by the istiʾnāf. Making the difference between the ʿaṭf al-bayān and something that is not categorized at this point in the text as badal, Nevertheless, the author of the Kitāb indicates for one case that it can be a badal or a ʿaṭf bayān, which shows that he does not really have the idea of the segmentation by istiʾnāf… (cf. Sībawayhi Kitāb II,191). 22 This correlation is, however, quite relevant, as Larcher recalls it:

Especially remarkable is the case of "disjunction" called "resumption" (istiʾnāf), because the second clause is to be understood as a response (jawāb) to an implicit question (suʾāl) suggested by the first, as in the following verse: qāla lī kayfa ʾanta qultu ʿalīlū/saharun dāʾimun waḥuznun ṭawīlū ("'How are you?' he asked me. 'Unwell! Permanent insomnia and prolonged melancholy!' I replied"); saharun dāʾimun waḥuznu ṭawīlū responds in fact to a question like mā bāluka ʿalīlan ("What maladies do you have?") or else mā sababu ʿillatika ("What is the cause of your malady?"). We see, from these few examples, that if "conjunction" is defined as a syntactic coordination, then "disjunction" could be interpreted as a semantic coordination, in the sense of [START_REF] Bally | Linguistique générale et linguistique française[END_REF]: the two disjoint clauses are in the semantic relation of topic to comment and the comment implicitly makes reference to the topic: "He is dead (and, because he is dead,) may Allah take pity on him!"; "(They say that they do nothing but mock, but) it is Allah who mocks them; [I am] sick; (you are going to ask me from what): from permanent insomnia and prolonged melancholy." (Larcher 2013: 195) 22 Fa-hāḏihi al-ʾasmāʾ al-mubhama ʾiḏā fassartahā taṣīru bi-manzila "ʾay" ka-ʾannaka ʾiḏā ʾaradta ʾan tufassirahā la yaǧuz laka ʾan taqifa ʿalayhā wa-ʾinnamā qulta "yā hāḏā ḏā lǧumma" li-ʾanna "ḏā l-ǧumma" lā tūṣafu bihi al-ʾasmāʾ al-mubhama ʾinnamā yakūnu badal ʾaw ʿaṭfan ʿalā al-ism.

The term "response" indeed implies that of "discourse's resumption" and therefore of segmentation. On the contrary, in the case of the ʿaṭf al-bayān, the juncture seems so strong that Talmon notes among the distinctions to be made between ṣifa and ʿaṭf (and thus ʿaṭf al-bayān) that the ṣifa can follow an implicit ʾaʿnī ("I mean"), which is impossible in the case of the ʿaṭf (cf. Talmon 1981: 287, fn. 14). 23

Conclusion

In his Syntaxe de l'arabe classique, Pierre Larcher indicates that "the one thing missing element from traditional Arabic grammar is intonation" (Larcher 2017: 97). 24 We have just seen that this is true concerning the difference between ʿaṭf bayān and badal al-kull min al-kull, where the main element taken into account is of pragmatic nature. However, as I have just shown, the suprasegmental aspect can still be identified, and join a dichotomy which, once we have it in mind, we can no longer leave out of account: the distinction between segmentation and juncture. If a grammarian and logician like ʾAstarābāḏī is doubtful about the distinction between badal al-kull and ʿaṭf bayān, it is because at the written level, a fortiori at a time when punctuation did not exist, both can only be distinguished orally, and this is the strength of Ibn Barhān al-ʿUkbarī who was the first to go beyond a literary analysis and frankly integrates the rhythm of speech in his reflexion.

But make no mistake, in the perspective of the Arabic grammatical tradition, as elsewhere, this suprasegmental criterion is in fact conditioned by the semantic and pragmatic criterion and is therefore secondary to it: as for the badal, it is because there is a referential uniqueness which makes the tābiʿ the primary element (semantic and pragmatic criterion) that there is takrīr, therefore istiʾnāf, that is to say pause and therefore segmentation (suprasegmental criterion); as for the ʿaṭf al-bayān, it is because there is a referential multiplicity (semantic and pragmatic criterion) that matbūʿ and tābiʿ are considered as a single noun (ism wāḥid) and as linked (muttaṣil) and that therefore no pause is made possible between the two, indicating then a juncture (suprasegmental criterion). This second criterion would, therefore, come (the addressee ignoring for example whether what is referred to is unique or multiple) to highlight objectively the semantic and pragmatic criterion which remains only subjective.

23

He refers to Sībawayhi Kitāb(2) I, 265 l. 5 where nevertheless the verb ʾaʿnī is not present. 24 "L'intonation est la grande absente de la grammaire arabe traditionnelle".

Without giving into precursorism, we still have to note that the description made by these medieval Arab grammarians can indeed match what contemporary linguists of French 25 say when they distinguish between close apposition (apposition liée) and loose apposition (apposition détachée). Indeed, in French grammar, among expansions of the noun (also called its modifiers) including the attributive adjective, construct state, etc., Riegel et al. indicate that they "have with the noun two types of relationships" (Riegel et al. 2004: 179, 26 also cf. 150) depending on whether these modifiers do restrict or not the extension of the noun. The first category includes the attributive adjective and among the second ones, which they generically call appositives "because non-restrictive modifiers are often separated from the rest of the utterance by intonation or by a pause, and in standard writing by a comma" (Riegel et al. 2004: 150). 27 These modifiers are then said to be "in detached position" (en position détachée, cf. [START_REF] Neveu | Études sur l'apposition : Aspects du détachement nominale et adjectival en français contemporain[END_REF][START_REF] Caddéo | L'apposition : analyse syntaxique de l'apposition nominale détachée dans divers registres de la langue parlée et de l'écrit en français contemporain[END_REF], a position that is "manifested in writing by the frame between two commas and orally by pauses (and sometimes by a 'bracketed' melody)" (Riegel et al. 2004: 190). 28 In the second category, the authors note that the appositive and its antecedent are in a relationship of referential uniqueness, which they illustrate with the example Paris, la capitale de la France, where "it is undeniable that the two defined expressions refer to the same reality" (Riegel et al. 2004: 190 29 ). 30

25

Being French, the author of these lines naturaly refers to French grammar and linguitics.

26

"entretiennent avec le nom deux types de relations". 27 "parce que les modificateurs non restrictifs sont souvent séparés du reste de l'énoncé par l'intonation ou par une pause, et dans l'écrit standard par une virgule". 28 "matérialisée à l'écrit par l'encadrement entre deux virgules et à l'oral par des pauses (et parfois par une mélodie "parenthétique")". We can add here an example from Yusuf Idris in his short story Riḥla where he writes kay ʾuḥissa ʾannī […] wa-ʾannī ʾašʿuru bi-l-ʾamān, ʾaḥlā wa-ʾaʿḏab wa-ʾamtaʿ ʾamān "so that I feel […] that I know the peace, the most beautiful, pleasant and delightful peace". Here, the presence of a comma is the manifestation in the written expression of the pause between the mubdal minhu and the badal.

29

"il est indéniable que les deux expressions définies désignent la même réalité". 30

Paradigmatically, it is a matter of distinguishing 1) at the G20 summit, President Obama and President Putin met… where "President", in an international context, is a multiple referent from 2) during his trip to the Lot (French area), the President, Macron, declared… where "President", in a national context, is a unique referent. It could also explain what Mejdell points out when dealing with the pronunciation of demonstratives without juncture. According to her, pronunciations like hāḏihi ʾal-madīna, that is to say without the elision of "the hamzat al-waṣl of the article on the head noun following" (Mejdell 2006:212-213), would reflect "the search for the right expression, le bon mot to be the head noun" (Mejdell 2006:221). This said, this nonjuncture could also make of the head noun a badal, then to be read as this, the town for example. I wish here to warmly thank Michael G. Carter for this reference as well as for his reading of this article, drastically approving its English, and also to our colleague, Emilie Coulon.

Even if, in French (or other languages like English or Swedish for example), things are not so clear-cut (cf. [START_REF] Rioul | Les appositions dans la grammaire française[END_REF][START_REF] Lindqvist | Apposition détachée ou liée ? Étude contrastive françaissuédois sur des combinaisons de Npr et de Nc[END_REF][START_REF] Lindqvist | Sur le rôle du nom commun dans le choix entre les appositions des trois types « le président Obama[END_REF], we will recognize in the non-restrictive modifiers the description of the Arabic badal al-kull min al-kull, not only because of its explicit description by the medieval grammarians who make it an element in a relationship of referential uniqueness with the term to which it is apposed, but also because of their use of takrīr and istiʾnāf which effectively imply their separation from the term to which they are apposed through starting again and the associated pause.

We will then recognize in the first category, that of restrictive modifiers, those features which ʿaṭf al-bayān shares with the ṣifa, that is to say the adjective, namely its function of restricting the extension of the noun, the ʿaṭf al-bayān being the most often described as ʾaḫaṣṣ min al-ʾawwal, as ʾašhar alismayn (cf. Ǧurǧānī ŠǦ 277, Zamaḫšarī ʾUnmūḏaǧ 20), and ʾaʿraf minhu (cf. Ǧurǧānī ŠǦ 277), but which also shares with the ṣifa the feature of not being orally separated from the term to which it is apposed.

In grammatical traditions like the French one for instance, this recognition of the double status of the apposition as either close or loose only manifests itself during 16th century (cf. Neveu 1998: 20). So here, again without giving in to precursorism, we have, in Arabic grammar, the early trace of a distinction between these two types of apposition, according to the same semantic and pragmatic criteria and with therefore the same suprasegmental consequences.

Bibliography

  Ibn al-Ḥāǧib (d. 646/1249) also discusses the difference between the two and likewise connects it to the takrīr: "the badal is considered as the repetition in all of its cases" (al-badal fī ḥukm al-takrīr fī ǧamīʿ ʾamṯālihi, Ibn al-Ḥāǧib ʾĪḍāḥ I, 431). As for the badal, Ibn ʿUṣfūr (d. 669/1271) also notes the feature of repetition since he says: When you say qāma zaydun ʾaḫūka […] it is as you said qāma ʾaḫūka having retracted what you first said, zayd […] and […] what indicates this is the repetition of the operator with the badal as in marartu bi-zaydin bi-ʾaḫīka. Allah the Almighty said (…) (Q. 7/75, cf. below). (ʾiḏā qulta "qāma zaydun ʾaḫūka" […] fa-ka-ʾannaka qulta "qāma ʾaḫūka" fa-ʾaḍrabta ʿan qawlika ʾawwalan "zayd" […] wa-[…] allaḏī yadullu ʿalā ḏālika takrīr al-ʿāmil maʿa al-badal fī naḥw "marartu bi-zaydin bi-ʾaḫīka" qāla allāh taʿālā (…), Ibn ʿUṣfūr ŠǦ I, 251) Ibn Hišām al-ʾAnṣārī (d. 761/1360), in his Sabīl al-hudā, deals with the two (cf.

  is the ʿaṭf al-bayān. (iʿlam ʾanna al-tābiʿ ʾimmā ʾan yakūna mukammilan lil-ʾawwal wa-ʾimmā ʾallā yakūna mukamillan lahu fa-l-laḏī lā yakūnu mukammilan li-l-ʾawwal huwa al-maʿṭūf bi-ḥarf al-ʿaṭf wa-l-laḏī yakūnu mukammilan li-l-ʾawwal huwa ʾimmā ʾan yakūna fī taqdīr ǧumlatayn ʾaw fī taqdīr ǧumla wāḥida fa-l-laḏī yakūnu fī taqdīr ǧumlatayn huwa al-badal[…] wa-l-laḏī yakūnu fī taqdīr ǧumla wāḥida ʿalā ḍarbayn […] fa-l-ʾawwal al-tawkīd wa-l-ṯānī ʿaṭf al-bayān, Ibn al-Dahhān al-Baġdādī Ġurra II, 854)

  = Raḍī al-Dīn Muḥammad b. al-Ḥasan al-ʾAstarābāḏī, Šarḥ Kāfiyat Ibn al-Ḥāǧib. Ed. by ʾImīl Badīʿ Yaʿqūb. Bayrūt: Dār al-kutub al-ʿilmiyya, 5 vol., 1419/1998. Baṭalyawsī, Rasāʾil = ʾAbū Muḥammad ʿAbd Allāh b. Muḥammad Ibn al-Sīd al-Baṭalyawsī, Rasāʾil fī al-luġa. Ed. by Walīd Muḥammad al-Sarāqabī. Al-Riyāḍ: Markaz al-Malik Fayṣal li-l-buḥūṯ wa-l-dirāsāt al-ʾislāmiyya, 1428/2007. Ġalāyīnī, Ǧāmiʿ = Muṣṭafā b. Muḥammad Salīm al-Ġalāyīnī, Ǧāmiʿ al-durūs al-ʿarabiyya. Ed. by ʿAbd al-Munʿim Ḫalīl ʾIbrāhīm. Bayrūt: Dār al-kutub al-ʿilmiyya, 1421/2000. Ǧāmiʿ al-ʿulūm, Kitāb šarḥ al-Lumaʿ fī al-naḥw = ʾAbū al-Ḥasan ʿAlī b. al-Ḥusayn b. ʿAlī al-ʾAṣfahānī al-Bāqūlī al-maʿrūf bi-Ǧāmiʿ al-ʿulūm, Kitāb šarḥ al-Lumaʿ fī al-naḥw. Ed. by Muḥammad Ḫalīl Murād al-Ḥarbī. Bayrūt: Dār al-kutub al-ʿilmiyya, 1428/2007.

  lahu ʾillā ʾannahu laysa bi-muštaqq min al-fiʿl bi-ḫilāf al-ṣifa wa-yušbihu fī al-lafẓ al-badal ʾillā ʾannahu yufāriquhu min ḥayṯu ʾanna albadal fī taqdīr takrīr al-ʿāmil wa-hāḏā bi-ḫilāfihi wa-yatabayyanu ḏālika fī bāb al-nidāʾ ʾiḏā qulta "yā ʾaḫānā zaydan" ʾin ǧaʿalta "zaydan" ʿaṭf bayān naṣabta li-ʾannaka ʾaqamtahu maqām "ʾaḫānā" wa-ʾin ǧaʿalta badalan qaddarta takrīr "yā" fa-qulta "yā ʾaḫānā zaydu" ka-ʾannaka qulta "yā zaydu", Ǧāmiʿ al-ʿulūm Kitāb šarḥ al-Lumaʿ fī al-naḥw 261)In his great commentary on the Mufaṣṣal Ibn Yaʿīš repeats the elements of badal by Zamaḫšarī, who, like other grammarians, emphasizes its syntactic independence and connects it with repetition, for which Ibn Yaʿīš then provides crystal clear examples:

and cf. 148-149 for possible translations of kalām). mubayyinan When you say marartu bi-ʾaḫīka zaydin, it is implicitly [saying] marartu bi-ʾaḫīka bi-zaydin, and when you say raʾaytu ʾaḫāka zaydan, its implicit meaning is raʾaytu ʾaḫāka raʾaytu zaydan. (ʾiḏā qulta "marartu bi-ʾaḫīka zaydin" taqdīruhu "marartu bi-ʾaḫīka bi-zaydin" wa-ʾiḏā qulta "raʾaytu ʾaḫāka zaydan" fa-taqdīruhu "raʾaytu ʾaḫāka raʾaytu zaydan", Ibn Yaʿīš ŠM II, 264)

  Ibn Barhān al-ʿUkbarī ŠL I, 229). But further on, this time about the ʿaṭf al-bayān, he says:If you ask: why you did not treat this section of the appositives as a badal, we will say that the adjectival qualifier is directly joined in the utterance to the qualified element, that it is not considered as a new utterance and that the same is true of the situation of the ʿaṭf al-bayān. Also, when you say qāma hāḏā zaydun "this one Zayd got up" by constructing the utterance the mention of zayd16 and not disassociating it from hāḏā, it is a ʿaṭf al-bayān. If you make of it [utterance] a new one, as if you said qāma hāḏā qāma zaydun "this one got up, Zayd got up", it is then a badal.

	14	For this term in Farrāʾ (d. 207/822), cf. Kasher 2014 and also Larcher 2013:195, but also
		Kinberg 1996: 28-32 and notably his definition of istʾanafa: "to begin (a new unit which is:
		1. Separated in pronunciation from the preceding unit" (1996:29) as well as the statement
		of Farrāʾ: wa-qawluhu "wa-mā ʾarsalnā min rasūlin ʾillā bi-lisāni qawmihi li-yubayyina
		lahum" … ṯumma qāla ʿazza wa-ǧalla "fa-yuḍillu -llāhu man yašāʾu" fa-rufiʿa li-ʾanna al-
		niyya fīhi al-istiʾnāf lā al-ʿaṭf ʿalā ma qablahu (1996:30) where, here at least, Farrāʾ clearly
		contrasts ʿaṭf with istiʾnāf. In this paper, therefore,, resumption will denote a new start,
		implying a pause before it.
	15	It has the same importance elsewhere, notably for Durkheim when he says that we must
		treat social facts as things (cf. Durkheim 1988:77 and 120; Pouillon 1987:112 for French and
		Durkheim 1982:35 and 69 for English).

zaydan raʾsahu" fa-l-ʾaṣl "ḍarabtu zaydan ḍarabtu raʾsahu", (fa-ʾin qulta hallā ǧaʿalta hāḏā al-faṣl min al-tawābiʿ badalan qulnā ʾinna al-ṣifa yubnā lahā al-kalām ʿalā ḏikr bayān muttaṣil fī al-mawṣūf wa-laysat fī taqdīr kalām mustaʾnaf wa-ka-ḏālika manzilat ʿaṭf al-bayān fa-ʾiḏā qulta "qāma hāḏā zaydun" wa-banayta al-kalām ʿalā ḏikr zayd wa-lam taǧʿalhu munqaṭiʿan min "hāḏā" fa-huwa ʿaṭf al-bayān wa-ʾin ǧaʿaltahu mustaʾnafan wa-ka-ʾannaka qulta "qāma hāḏā qāma zaydun" fa-huwa badal, Ibn Barhān al-ʿUkbarī ŠL I, 235)

  Sībawayhi writes:As for what Ruʾba says, it is the fact that he made of naṣran a ʿaṭf al-bayān and he put it in the accusative as if he had said yā zaydu zaydan. As to what ʾAbū ʿAmr says, it is as if he had started the vocative again [i.e. yā zaydu yā zaydu l-ṭawīlu]. (wa-ʾammā qawl ruʾba fa-ʿalā ʾannahu gaʿala "naṣran" ʿaṭf al-bayān wa-naṣabahu ka-ʾannahu ʿalā qawlihi "yā zaydun zaydan" wa-ʾammā qawl ʾabī ʿamr fa-ka-ʾannahu istaʾnafa al-nidāʾ,Sībawayhi Kitāb II, 187)

"and thou shalt surely direct them in to the right way, the way of God"(Sale 1877:397).


Thalita S Galhardo

Anderson K Ueno

Thaís A Costa-Silva

André G Tempone

Wagner A Carvalho

Cedric Fischmeister

Christian Bruneau

Dalmo Mandelli
email: dalmo.mandelli@ufabc.edu

João Henrique

G Lago

Thaís A Costa-Silva

João Henrique G Lago

New derivatives

Keywords: Trypanosoma cruzi, neolignans, plasma membrane; mitochondrial membrane

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

Currently, about one billion people in the world suffer from at least one of the 20 diseases that are classified by WHO as Neglected Tropical Diseases (NTDs) [START_REF] Peeling | Re-imagining the future of diagnosis of Neglected Tropical Diseases[END_REF]. These diseases represent a major cause of morbidity and mortality, mainly in tropical regions of the world and, are considered neglected due to a lack of financial investments in the Research & Development for development of new drugs [START_REF] Chatelain | Drug discovery and development for neglected diseases: the DNDi model[END_REF]. A recent study showed that among the tropical parasitic diseases that cause mortality in the Brazilian population, Chagas disease deserves important attention [START_REF] Martins-Melo | Mortality from neglected tropical diseases in Brazil, 2000-2011[END_REF]. Caused by the flagellate protozoan parasite Trypanosoma cruzi, there are only two available drugs for the treatment: benznidazole and nifurtimox [START_REF] Sales Junior | Experimental and clinical treatment of Chagas disease: A review[END_REF]. To contribute to novel therapies, the chemistry of natural products plays an important role in the search for bioactive compounds [START_REF] Conserva | Butenolides from Nectandra oppositifolia (Lauraceae) displayed anti-Trypanosoma cruzi activity via deregulation of mitochondria[END_REF][START_REF] Londero | copy macrocarpa (Annonaceae) against trypomastigotes of Trypanosoma cruzi: Effect of octadec-9-ynoic acid in plasma membrane electric potential[END_REF][START_REF] Grecco | Antitrypanosomal activity and evaluation of the mechanism of action of dehydrodieugenol isolated from Nectandra leucantha (Lauraceae) and its methylated derivative against Trypanosoma cruzi[END_REF]. The genus Nectandra is composed of approximately 120 species of predominantly tropical distribution, with wide diversity in the Brazilian Atlantic Forest [START_REF] Grecco | Update: biological and chemical aspects of Nectandra genus (Lauraceae)[END_REF][START_REF] Baitello | Flora Fanerogâmica do Estado de São Paulo[END_REF]. Phytochemical studies performed with Nectandra species have shown great structural diversity of bioactive metabolites, including lignoids, alkaloids, and terpenoids [START_REF] Grecco | Update: biological and chemical aspects of Nectandra genus (Lauraceae)[END_REF]. N. leucantha, a species with occurrence in the Atlantic Forest of the São Paulo and the Espírito Santo States of Brazil, accumulated different neolignans formed by oxidative coupling of eugenol with antiinflammatory, antitumoral, and antiparasitic potential, especially against Leishmania infantum and Trypanosoma cruzi [START_REF] Grecco | Antitrypanosomal activity and evaluation of the mechanism of action of dehydrodieugenol isolated from Nectandra leucantha (Lauraceae) and its methylated derivative against Trypanosoma cruzi[END_REF][START_REF] Baitello | Flora Fanerogâmica do Estado de São Paulo[END_REF][START_REF] Quinet | Lauraceae in Lista de[END_REF][START_REF] Bittencourt-Mernak | Effects of eugenol and dehydrodieugenol B from Nectandra leucantha against lipopolysaccharide (LPS)-induced experimental acute lung inflammation[END_REF][START_REF] Sousa | Neolignans isolated from Nectandra leucantha induce apoptosis in melanoma cells by disturbance in mitochondrial integrity and redox homeostasis[END_REF][START_REF] Costa-Silva | Immunomodulatory and antileishmanial activity of phenylpropanoid dimers isolated from Nectandra leucantha[END_REF][START_REF] Grecco | Neolignans from leaves of Nectandra leucantha (Lauraceae) display in vitro antitrypanosomal activity via plasma membrane and mitochondrial damages[END_REF]. In the present work, two new methoxycarbonyl derivatives of dehydrodieugenol B and methyldehydrodieugenol B, both isolated from twigs of N. leucantha, were prepared via olefin cross-metathesis with methyl acrylate in the presence of a ruthenium-based catalyst. Obtained compounds were evaluated against extra (trypomastigote) and intracellular (amastigote) forms of T. cruzi. Moreover, the phenotypical mechanisms involved in the parasite death of these compounds in trypomastigotes of T. cruzi were also investigated.

Material and methods

General experimental procedures

Methylacrylate was purchased from Sigma-Aldrich and stored over 3 Å molecular sieves under an inert atmosphere. Dimethyl carbonate was purchased from Alfa-Aesar and was distilled under an inert atmosphere of argon and stored over 3Å molecular sieves.

Hoveyda-Grubbs II catalyst M72 (C627) was provided by Umicore. Column chromatography (CC) was performed with silica gel (230-400 mesh, Merck) and Sephadex LH-20 (Aldrich), while thin layer chromatography (TLC) separations were carried out on silica gel 60 PF254 (Merck). 1 H and 13 C nuclear magnetic resonance (NMR) spectra were recorded, respectively, at 400 and 100 MHz on a Bruker Avance III Ascend 400 spectrometer using CDCl3 (Sigma-Aldrich) as the solvent and using the residual signal of CHCl3 as the internal standard ( 7.26 vs TMS). Electrospray ionization -high resolution mass spectrometry (ESI-HRMS) data were measured on an Agilent 6510 Q-TOF LC/MS spectrometer, using an ESI ion source operating at positive mode. Elemental analysis was obtained in a Perkin-Elmer Elemental Analyzer model 2400 CHN. Infrared (IR) spectra were recorded with a Shimadzu FT-IR Prestige-21 instrument.

Accepted manuscript / Clean copy

Plant material

Fresh twigs of N. leucantha were collected at Cubatão city, São Paulo State, in March 2019 from the same previously studied species [START_REF] Sousa | Neolignans isolated from Nectandra leucantha induce apoptosis in melanoma cells by disturbance in mitochondrial integrity and redox homeostasis[END_REF][START_REF] Costa-Silva | Immunomodulatory and antileishmanial activity of phenylpropanoid dimers isolated from Nectandra leucantha[END_REF]. The plant species was identified by Dr. Euder G.A. Martins and a voucher specimen (EM357) has been deposited in the Herbarium of the Institute of Biosciences, University of São Paulo, SP, Brazil.

Extraction and isolation

Dried and powdered twigs of N. leucantha (200 g) were extracted with n-hexane (10 x 250 mL). Combined organic extracts were concentrated under reduced pressure to afford 7.5 g of crude extract. Part of this extract (1.5 g) was chromatographed over a silica gel column eluted with increasing amounts of EtOAc in n-hexane to afford five fractions (A -E). Fraction C (396 mg) was composed of pure 2. Part of the fraction D (375 mg) was chromatographed over Sephadex LH-20, eluted with CHCl3:MeOH 1:1, to afford pure compound 1 (287 mg).

Preparation of compounds 1a and 2a via olefin cross-metathesis reaction.

A dry and degassed Schlenk tube was loaded under argon with 50 mg of compound 1 or 2 (0.15 mmol, 1 equiv.), 1.6 mg of p-benzoquinone (1.5  10 -2 mmol), 56 μL of methyl acrylate (0.61 mmol, 4 equiv.), and 1.5 mL of dimethyl carbonate (DMC). Another dry and degassed Schlenk tube was loaded under argon with 1.9 mg of Hoveyda-Grubbs II catalyst (3  10 -3 mmol, 2 mol%) and 0.5 mL of DMC. The ruthenium catalyst was then Accepted manuscript / Clean copy taken by a syringe and was slowly added into the first Schlenk tube through the septum by means of a syringe pump for 2 h at 80°C. After addition, the reaction mixture was stirred at 80 °C for an additional time (3 h) [START_REF] Fernandes | Functionalization of (-)-β-pinene and (-)-limonene via cross metathesis with symmetrical internal olefins[END_REF]. After solvent evaporation under reduced pressure, products 1a or 2a were individually purified by chromatography column over silica gel eluted with increasing amounts of EtOAc in n-hexane. with 10% FBS and were maintained at 37 ºC in a 5% CO2-humidified incubator [START_REF] Rea | Soulamarin isolated from Calophyllum brasiliense (Clusiaceae) induces plasma membrane permeabilization of Trypanosoma cruzi and mytochondrial dysfunction[END_REF].

Methyl 4-{4-[2-hydroxy-3-methoxy-5-(4-methoxy-4-oxobut-2E-en-1-yl)phenoxy]-

Determination of anti-trypomastigote and anti-amastigote activity

The 50% effective concentration (EC50) of compounds 1, 1a, 2, and 2a against T.

cruzi was determined in trypomastigotes and amastigotes forms. Trypomastigotes were obtained from LLC-MK2 cultures previously infected. The parasites were counted in a Neubauer hemocytometer, seeded at 1 x 10 6 cells/well (96-well plates), and incubated with serial dilutions of the tested compounds (150 -1.71 µM), for 24 h at 37 ºC in a 5% CO2-humidified incubator, with benznidazole as the standard drug. The trypomastigote viability was evaluated by the resazurin (Sigma) assay [START_REF] Londero | copy macrocarpa (Annonaceae) against trypomastigotes of Trypanosoma cruzi: Effect of octadec-9-ynoic acid in plasma membrane electric potential[END_REF]. To determine the activity against intracellular amastigotes, peritoneal macrophages from BALB/c mice were infected with trypomastigotes forms of T. cruzi. The macrophages obtained from the Accepted manuscript / Clean copy Accepted manuscript / Clean copy peritoneal cavity of BALB/c mice were plated on a 16-well chamber slide (NUNC plate, Merck; 1 x 10 5 /well) and incubated for 24 h at 37 ºC in a 5% CO2-humidified incubator.

Trypomastigotes obtained as described above, were washed in RPMI-1640 medium, counted, and used to infect the macrophages (parasite:macrophage, ratio = 10:1). After 2 h of incubation at 37 ºC in a 5% CO2-humidified incubator, non-internalized parasites were removed by washing with the medium [START_REF] Rea | Soulamarin isolated from Calophyllum brasiliense (Clusiaceae) induces plasma membrane permeabilization of Trypanosoma cruzi and mytochondrial dysfunction[END_REF]. Compounds 1, 1a, 2, and 2a were individually incubated with infected macrophages (48 h at 37 ºC, 5% CO2) at different concentrations using benznidazole as the standard drug. At the end of the assay, slides were fixed with MeOH and stained with Giemsa prior to counting under a light microscope (EVOS M5000, THERMO). EC50 values were calculated as described [START_REF] Londero | copy macrocarpa (Annonaceae) against trypomastigotes of Trypanosoma cruzi: Effect of octadec-9-ynoic acid in plasma membrane electric potential[END_REF]. The data represent the mean of three independent assays, tested in duplicate. Infected macrophages without drug treatments were included as a negative control [START_REF] Rea | Soulamarin isolated from Calophyllum brasiliense (Clusiaceae) induces plasma membrane permeabilization of Trypanosoma cruzi and mytochondrial dysfunction[END_REF].

Determination of cytotoxicity against mammalian cells

The cytotoxicity determination of compounds 1, 1a, 2, and 2a was performed using NCTC cells-clone. The cells (6 x 10 4 cells/well, L929, passage 16) were seeded and incubated with tested compounds (200 -1.56 µM) for 48 h at 37 ºC in a 5% CO2 incubator.

The 50% cytotoxic concentrations (CC50) were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay [START_REF] Londero | copy macrocarpa (Annonaceae) against trypomastigotes of Trypanosoma cruzi: Effect of octadec-9-ynoic acid in plasma membrane electric potential[END_REF]. The optical density was determined in FilterMax F5 (Molecular Devices) at 570 nm. The selectivity index (SI) values were calculated for both forms of the parasite (trypomastigotes and amastigotes) using the equation: CC50 against L929 cells/EC50 against parasites. Cells without drug treatments were included as a negative control. The data represent the mean of two independent assays, tested in duplicate [START_REF] Rea | Soulamarin isolated from Calophyllum brasiliense (Clusiaceae) induces plasma membrane permeabilization of Trypanosoma cruzi and mytochondrial dysfunction[END_REF]. (CCCP) at 100 µM (C+) and untreated parasites (C-). Fluorescence was quantified by calculating the ratio between the channels BL2/BL1. *p < 0.05. The data represent the mean of three independent assays, tested in duplicate [START_REF] Costa-Silva | Ent-kaurane diterpenes isolated from n-hexane extract of Baccharis sphenophylla by bioactivity guided fractionation target the acidocalcisomes in Trypanosoma cruzi[END_REF].

Evaluation of Ca 2+ levels in T. cruzi trypomastigotes

Fluo-4 acetoxymethyl ester (Flu4-AM) probe was measured spectrofluorimetrically (excitation 360 nm and emission 500 nm) by 260 min of incubation after treatment of Accepted manuscript / Clean copy trypomastigotes with compounds 1a and 2a at IC50 value. Untreated trypomastigotes and treated with triton-X 100 (TX-100) at 0.5% were used as a negative (C-) and positive (C+) control, respectively. Fluorescence was reported as a percentage relative to untreated trypomastigotes (100%). Parasites without drug treatments were included as a negative control. The data represent the mean of three independent assays, tested in duplicate [START_REF] Costa-Silva | Ent-kaurane diterpenes isolated from n-hexane extract of Baccharis sphenophylla by bioactivity guided fractionation target the acidocalcisomes in Trypanosoma cruzi[END_REF].

Statistical analysis

EC50 and CC50 data represent the mean of three independent representative assays tested in duplicate and were calculated using sigmoid dose-response curves in Graph-Pad Prism 6.0 software (San Diego, CA, USA). Mechanism of action studies were analyzed using ANOVA test turkey for significance (p < 0.05).

Results and discussion

Previous studies demonstrated the anti-T. cruzi activity of neolignans dehydrodieugenol B (1) and methyldehydrodieugenol B (2), both isolated from Nectandra leucantha [START_REF] Grecco | Neolignans from leaves of Nectandra leucantha (Lauraceae) display in vitro antitrypanosomal activity via plasma membrane and mitochondrial damages[END_REF]. Further studies also indicated that different semi-synthetic compounds, especially those containing chemical differences of the allyl side chain, displayed higher anti-T. cruzi potential in comparison with natural products 1 and 2 [START_REF] Ferreira | Dehydrodieugenol B derivatives as antiparasitic agents: Synthesis and biological activity against Trypanosoma cruzi[END_REF]. Inspired by our previous works on cross-metathesis of acrylic derivatives with unsaturated natural products [20 -24] including 4-allylphenol substrates [START_REF] Bilel | Transformations of bio-sourced 4 hydroxyphenylpropanoids based on olefin metathesis[END_REF][START_REF] Bilel | Eugenol as a renewable feedstock for the production of polyfunctional alkenes via olefin cross metathesis[END_REF], the cross-metathesis reaction was conducted with natural dehydrodieugenol B (1) and its methyl ether (2). This

Accepted manuscript / Clean copy Accepted manuscript / Clean copy procedure, catalyzed by the second generation Hoveyda catalyst [START_REF] Garber | Efficient and Recyclable Monomeric and Dendritic Ru-Based Metathesis Catalysts[END_REF] and dimethyl carbonate as solvent [START_REF] Bilel | Cross metathesis transformations of terpenoids in dialkyl carbonate solvents[END_REF][START_REF] Miao | Dimethyl carbonate: an ecofriendly solvent in ruthenium-catalyzed olefin metathesis transformations[END_REF] afforded new compounds 1a and 2a both containing an additional methoxycarbonyl group at C-9/C-9' (Figure 1) in 42 and 56% yield, respectively.

ESI-HRMS spectra of compounds 1a and 2a, showed [M + Na] + ion peaks at m/z 465.1519 and 479.1677, respectively, compatible with molecular formulas C24H26O8 and C25H28O8. 1 H NMR spectra of both derivatives exhibited similarities to those observed for compounds 1 and 2, especially in the region of aromatic hydrogens in the range 6.88 -6.24. However, the main detected difference was the presence of two coupled systems at 7.09 (ddt, J = 15.7 and 6.7 Hz) and 5.84 (d, J = 15.7 Hz), assigned to H-8/8´ and H-9/9´, respectively. Based on the value of the coupling constant between H-8/8' and H-9/9' (15.7 Hz), it was possible to infer the E stereochemistry of both double bonds [START_REF] Martin | The stereochemistry of double bonds[END_REF]. Furthermore, the presence of one singlet at 3.71 (6H) was indicative of two additional methoxy groups, attributed to H-12/12´. Analysis of 13 and 2 and derivatives 1a and 2a, the inclusion of the methoxycarbonyl group at the allyl side chain of natural neolignans provided considerable impact on parasite activity, especially against amastigote forms of T. cruzi. As presented in Table 1, an increment in the potency of the derivative 1a (EC50 of 10.2 μM) in comparison to natural product 1 (EC50 of 86.5 μM) was observed (p<0.05), but with higher toxicity against NCTC cells (CC50 of 139.8 μM) (p<0.05), a similar effect already observed with other chemically related phenolic derivatives [START_REF] Grecco | Antitrypanosomal activity and evaluation of the mechanism of action of dehydrodieugenol isolated from Nectandra leucantha (Lauraceae) and its methylated derivative against Trypanosoma cruzi[END_REF]. The increment in the bioactivity caused by chemical derivatization was more intense when EC50 values of compounds 2 and 2a were compared (p<0.05).

As observed, natural product 2 showed to be inactive against both trypomastigote and amastigote forms of T. cruzi (EC50 > 150 μM) while compound 2a exhibited excellent potential (EC50 of 6.1 μM) and reduced toxicity (CC50 > 200 μM). Considering these results, it could be suggested that methoxycarbonyl unity plays an important role in the anti-T. cruzi activity, especially against amastigote forms of this parasite. Based on the obtained results and the criteria preconized by the Drug for Neglected Diseases initiative (DNDi) [START_REF] Don | Pathogenesis of Chagas' disease: parasite persistence and autoimmunity[END_REF] for the discovery of new hit compounds for T. cruzi that include EC50 values Accepted manuscript / Clean copy lower than 10 µM against amastigotes and SI >10, it is possible to suggest that derivative 2a could be considered a hit compound for future chemical optimizations for Chagas disease.

Considering the potency of compounds 1a and 2a, different assays were performed to evaluate their mechanism of action on the trypomastigotes. The plasma membrane is the first contact of an exogenous compound with the cell and damage to its structure can lead to irreversible effects. Using the SYTOX Green fluorescent probe, compounds 1a and 2a showed no interference in the permeability of the plasma membrane permeability (data not shown), differently from that observed for 1-[(7S)-hydroxy-8-propenyl]-3-[3'methoxy-1'-(8'-propenyl)-phenoxy]-4,5-dimethoxybenzene, a natural neolignan isolated from N. leucantha, but structurally different of compound 2 due to the presence of an additional hydroxyl group at C-7 position [START_REF] Grecco | Neolignans from leaves of Nectandra leucantha (Lauraceae) display in vitro antitrypanosomal activity via plasma membrane and mitochondrial damages[END_REF]. However, compounds 1a and 2a caused a significant depolarization of the plasma membrane electric potential, similar to that observed in chemically related neolignans isolated from N. leucantha [START_REF] Grecco | Neolignans from leaves of Nectandra leucantha (Lauraceae) display in vitro antitrypanosomal activity via plasma membrane and mitochondrial damages[END_REF] as well as their semi-synthetic derivatives [START_REF] Ferreira | Dehydrodieugenol B derivatives as antiparasitic agents: Synthesis and biological activity against Trypanosoma cruzi[END_REF]. As observed in figure 2, compound 1a induced the disturbance after 2 h of incubation (p < 0.001), whereas with compound 2a it was only after 1 h of incubation (p < 0.05). This effect might be ascribed to a transient depolarization caused by 2a in the membrane, which reverted to a homeostasis after this period. The membrane potential is the result of the movement of numerous ions through ion channels and transporters, resulting in different electrostatic charges across the cell membrane.

The maintenance of plasma membrane integrity is essential for normal cell viability and function and damage can directly affect the homeostasis [START_REF] Wright | Generation of resting membrane potential[END_REF].

Differently from the mammalian cells, Trypanosomatidae parasites present a unique mitochondrion, being considered an interesting target for drug discovery studies

Accepted manuscript / Clean copy [START_REF] Fidalgo | Mitochondria and trypanosomatids: Targets and drugs[END_REF]. Using JC1 as a fluorescent probe, compounds 1a and 2a showed a depolarization of the mitochondrial membrane potential (ΔΨm) after 1 h of incubation (Figure 3A).

Undoubtedly, cell life critically depends on the maintenance of the mitochondrial membrane potential. If the repair machinery starts a robust response, this electric potential can be restored. Compounds 1a and 2a were incubated for more than 1 h, but depolarization effect continued even after 2 h treatment (Figure 3B). The ΔΨm is generated by proton pumps and is an essential component in the process of energy storage during oxidative phosphorylation. However, continued changes may be deleterious, resulting in the loss of cell viability [START_REF] Zorova | Mitochondrial membrane potential[END_REF].

Intracellular calcium participates in the different processes including cell differentiation, proliferation, and motility. It can be altered in response to a number of stimuli including chemical, electrical, and physical. Alterations of these levels can trigger specific cellular responses, affecting cell viability [START_REF] Bagur | Intracellular Ca 2+ sensing: Its role in calcium homeostasis and signaling[END_REF]. In this study, the T. cruzi Ca 2+ levels after treatment with compounds 1a and 2a were also investigated, but no alterations could be observed after 2 h (data not shown), suggesting other initial targets rather than calcium storage organelles like acidocalcisomes.

Conclusion

In this work, dehydrodieugenol B (1) and its methyl ether (2), both isolated from N. leucantha, were used as starting material for the preparation of derivatives 1a and 2a via olefin cross-metathesis reaction. These modified compounds showed a promising trypanocidal effect, with antiparasitic selectivity and affecting the unique mitochondrial system of the parasite. Especially for compound 2a, insertion of the methoxycarbonyl study is an activity within the Research Network Natural Products against Neglected Diseases (ResNetNPND: http://www.resnetnpnd.org/).

Accepted manuscript / Clean copy group resulted in a promising efficiency without mammalian cytotoxicity. Mechanism of action studies of both compounds 1a and 2a demonstrated a depolarization of the plasma membrane potential, followed by a mitochondrial membrane potential collapse. On the other hand, neither Ca 2+ level nor ROS alterations were observed after a short-time incubation. Considering the hit criteria for new candidates, tested compounds but especially derivative 2a, could be considered prototypes for optimization studies for the design of new derivatives against T. cruzi. Accepted manuscript / Clean copy EC50 -50% effective concentration, CC50 -50% cytotoxic concentration, SI -selectivity index, calculated by the ratio CC50 against NCTC cells/EC50 against parasites (trypomastigote and amastigote forms), NA -not active at the higher tested concentration (150 M).

Accepted manuscript / Clean copy

2. 9 .

 9 Evaluation of plasma membrane electric potential (ΔΨp) in T. cruzi trypomastigotes Evaluation of plasma membrane electric potential (ΔΨp) with bis-(1,3diethylthiobarbituric acid)trimethine oxonol (DISBAC2 -3) probe in T. cruzi trypomastigotes treated was performed for 2 h with compounds 1a and 2a. Controls of the assay were trypomastigotes treated with gramicidin (0.5 µg/mL) (positive control -C+) and untreated parasites (negative control -C-). Fluorescence was quantified by calculating the mean percentages of untreated (0%) and gramicidin-treated (100%) parasites. Evaluation of mitochondrial membrane potential in T. cruzi trypomastigotes was performed with 1a and 2a labeled with JC-1 probe (0.2 μM). Parasites without drug treatments were included as a negative control. The fluorescence was measured in a flow cytometer (ATTUNE) after 1 and 2 h of incubation with tested compounds. Controls of the assay were trypomastigotes treated with carbonylcyanide m-chlorophenylhydrasone

Figure 1 .

 1 Figure 1.

Figure 1 .

 1 Figure 1. Chemical structures of derivatives 1a and 2a (in red -addition of

Figure 2 .

 2 Figure 2. Evaluation of plasma membrane electric potential (ΔΨp) with DISBAC2 (3)

Figure 3 .

 3 Figure 3. Evaluation of mitochondrial membrane potential (ΔΨm) in T. cruzi

  Hz, H-2'),[START_REF] Londero | copy macrocarpa (Annonaceae) against trypomastigotes of Trypanosoma cruzi: Effect of octadec-9-ynoic acid in plasma membrane electric potential[END_REF].45 (1H, d, J = 1.8 Hz, H-2), 6.24 (1H, d, J = 1.8 Hz, H-6), 5.85 (1H, dt, J = 15.5 and 1.5 Hz, H-9), 5.77 (1H, dt, J = 15.6 and 1.5 Hz, H-9'), 3.87 (3H, s, H-10/10'), 3.82 (3H, s, H-13), 3.73 (3H, s, H-12), 3.71 (3H, s, H-12'), 3.50 (2H, dd, J = 6.7Research Ethics Commission (project CEUA-IAL 05/2018), in agreement with the Guide for the Care and Use of Laboratory Animals from the National Academy of Sciences.

	2.6. Parasites and mammalian cell maintenance
	T. cruzi trypomastigotes (Y strain) were maintained in Rhesus monkey kidney cells
	3-(LLC-MK2 -ATCC CCL 7), using RPMI-1640 medium supplemented with 2% fetal bovine
	methoxyphenyl}but-2E-enoate (1a): yellowish oil (yield 42%). IR (KBr) max 3421, 2947, serum (FBS) at 37 ºC in a 5% CO2-humidified incubator. Murine conjunctive cells (NCTC
	2837, 1720, 1654, 1585, 1508, 1429, 1269, 1211, 1155, 1093, 1033, 827 cm -1 ; 1 H NMR
	(CDCl3, 400 MHz): ppm 7.09 (1H, dt, J = 15.7 and 6.7 Hz, H-8), 7.02 (1H, dt, J = 15.5
	and 6.8 Hz, H-8') 6.88 (1H, d, J = 8.1 Hz, H-6'), 6.76 (1H, d, J = 8.1 Hz, H-3'), 6.69 (1H,
	d, J = 8.1 Hz, H-2'), 6.46 (1H, d, J = 1.7 Hz, H-2), 6.35 (1H, d, J = 1.7 Hz, H-6), 5.84 (1H,
	br d, J = 15.7 Hz, H-9 ), 5.81 (br s, OH) 5.77 (1H, br d, J = 15.5 Hz, H-9'), 3.89 (3H, s,
	H-10), 3.85 (3H, s, H-10'), 3.73 (3H, s, H-12), 3.71 (3H, s, H-12'), 3.49 (2H, d, J = 6.8 Hz,
	H-7'), 3.37 (2H, d, J = 6.7 Hz, H-7); 13 C NMR (CDCl3, 100 MHz): /ppm 167.0 (C-11/11'),
	150.7 (C-5'), 148.2 (C-5), 147.8 (C-8'), 147.5 (C-8), 144.6 (C-3), 144.5 (C-4'), 135.7 (C-
	4), 134.2 (C-1'), 128.8 (C-1), 122.1 (C-9'), 121.9 (C-9), 121.3 (C-2'), 119.8 (C-3'), 113.2
	(C-6'), 112.1 (C-6), 107.5 (C-2), 56.4 (C-10), 56.2 (C-10'), 51.7 (C-12), 51.6 (C-12'), 38.3
	(C-7/7'); ESI-HRMS m/z 465.1519 [M + H] + (calcd. for C24H26O8Na 465.1525); Anal. C
	64.92, H 6.01% (calcd. for C24H26O8, C 65.15, H 5.92%).

Accepted manuscript / Clean copy Accepted manuscript / Clean copy 2.4.2. Methyl 4-{4-[2,3-dimethoxy-5-(4-methoxy-4-oxobut-2E-en-1-yl)phenoxy]-3-methoxyphenyl}but-2E-enoate (2a): yellowish oil (yield 56%). IR (KBr) max 3421, 2947, 2846, 1724, 1658, 1593, 1508, 1433, 1267, 1213, 1157, 1085, 1031 cm -1 ; 1 H NMR (CDCl3, 400 MHz): /ppm 7.10 (1H, dt, J = 15.5 and 6.8 Hz, H-8), 7.02 (1H, dt, J = 15.6 and 6.7 Hz, H-8'), 6.82 (1H, d, J = 8.1 Hz, H-6'), 6.76 (1H, d, J = 1.8 Hz, H-3'), 6.68 (1H, dd, J = 8.1 and 1.8 and 1.0 Hz, H-7'), 3.37 (2H, dd, J = 6.8 and 1.2 Hz, H-7); 13 C NMR (CDCl3, 100 MHz): /ppm 167.0 (C-11), 166.9 (C-11'), 153.9 (C-5'), 150.9 (C-4'), 150.8 (C-5), 147.6 (C-8), 147.4 (C-8'), 144.5 (C-3), 138.6 (C-4), 133.9 (C-1'), 133.2 (C-1), 122.1 (C-9'), 122.0 (C-9), 121.2 (C-2'), 119.8 (C-3'), 113.3 (C-6'), 111.7 (C-6), 107.8 (C-2), 61.1 (C-13), 56.3 (C-10), 56.1 (C-10'), 51.6 (C-12/12'), 38.4 (C-7), 38.5 (C-7'); ESI-HRMS m/z 479.1677 [M + Na] + (calcd. for C25H28O8Na 479.1682); Anal. C 65.55, H 6.20% (calcd. for C25H28O8, C 65.78, H 6.18%).

2.5. Experimental animals

BALB/c mice were obtained by the animal breeding facility at the Instituto Adolfo Lutz -São Paulo State, Brazil. The animals were maintained in sterilized boxes with absorbent material under a controlled environment and received water and food ad libitum. BALB/c mice were used to obtain peritoneal macrophages, and for T. cruzi maintenance infection

[START_REF] Grecco | Isolation of an antileishmanial and antitrypanosomal flavanone from the leaves of Baccharis retusa DC. (Asteraceae)[END_REF]

. Animal procedures were performed with the approval of the clone 929, ATCC) and LLC-MK2 were maintained in RPMI-1640 supplemented with 10% FBS at 37 ºC in a 5% CO2-humidified incubator. Macrophages were obtained from the peritoneal cavity of BALB/c mice by washing them with RPMI-1640 medium supplemented

Table 1

 1 the highest tested concentration of 200 µM. Considering the selectivity index (SI), which is the relation between the cytotoxicity in NCTC cells and the activity against trypomastigote forms, it was possible to calculate values of 10.3 and > 8.7 for compounds 1a and 2a, respectively. When tested against the intracellular amastigotes, the most relevant clinical form of T. cruzi, compounds 1a and 2a exhibited high potential, with EC50 values of 10.2 and 6.1 μM, respectively, superior to the positive control benznidazole (IC50 of 18.7 μM) (p<0.05). Concerning the toxicity against NCTC cells, compounds 1a and 2a displayed SI values of 13.7 and > 32.8, respectively, higher than those calculated for benznidazole (SI > 10.7) (p<0.05). Considering chemical structures of natural products 1

. Furthermore, compound 1a showed moderate cytotoxicity (CC50 of 139.8 M) while compound 2a was non-toxic Accepted manuscript / Clean copy to

Table 1 .

 1 Anti-T. cruzi activity (trypomastigotes and amastigotes) and cytotoxicity (NCTC cells) for positive control benznidazole (BZD), for natural products 1 and 2 as well as for

	derivatives 1a and 2a.
		EC50 (M)	CC50 (M)	SI
		trypomastigote	amastigote	NCTC	trypomastigote	amastigote
	1	38.6 ± 13.6	86.5 ± 10.4	> 200	> 5.2	> 2.3
	1a	13.5 ± 11.0	10.2 ± 2.8	139.8 ± 19.3	10.3	13.7
	2	NA	NA	> 200	-	-
	2a	23.0 ± 2.1	6.1 ± 0.7	> 200	> 8.7	> 32.8
	BZD	5.5 ± 0.9	18.7 ± 4.1	> 200	> 36.4	> 10.7

Acknowledgments

The authors acknowledge CAPES-COFECUB for support to the project no. PHC 884-17 (France) and 883/2017 (Brazil), CNPq (project 312288/2019-0 and 404843/2018-2); FAPESP (2021/02789-7, 2021/04464-8, 2018/01258-5, 2018/07885-1, 2018/10279-6, 2017/24931-4, 2017/17044-1, and 2016/05006-5), CAPES (Finance Code 001), Institutional Internationalization Program CAPES-PrInt/UFABC and the Multi-User Central Facilities (CEM/UFABC) for the experimental support. J.H.G.L., A.G.T. and D.M. also thank CNPq for fellowships. Finally, T. S. G. thanks the CAPES-COFECUB grant 88887.198050/2018-00. Umicore is thanked for supplying the ruthenium catalyst. This

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Accepted manuscript / Clean copy

SUPPLEMENTARY INFORMATION


S Conforti
email: conforti@omega.in2p3.fr

A Cabrera

C Taille

F Dulucq

M Grassi

G Martin-Chassard

A Noury

C Santos

N Seguin-Moreau

M Settimo

C De

La Taille

CATIROC, a multichannel front-end ASIC to read out the 3 PMTs (SPMT) system of the JUNO experiment

Keywords:

niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

The Jiangmen Underground Neutrino Observatory (JUNO) is a multipurpose neutrino experiment designed to determine neutrino mass hierarchy with a 20-thousand-ton liquid scintillator spherical detector at about 700-m deep underground. The detection principle in JUNO is based on the observation of the light emitted in the Inverse Beta Decay in the liquid scintillator volume by array of large photomultipliers (LPMT). To reach the expected sensitivity of mass hierarchy, the energy resolution has to be better than 3% at 1 MeV. In order to achieve this target the LPMT will have to cover approximately 75% of the inner surface of the sphere, elevating the number of necessary LPMTs to 18,000. In order to improve the calorimetry control of the LPMT system 25,000 small 3-in. small photo-multipliers (SPMTs) will be installed between the LPMTs [START_REF] Miao | Double calorimetry system in JUNO experiment[END_REF]. The size of these PMTs is chosen to operate in photon-counting mode for all events inside the detector. The large number of SPMTs increases the density and the complexity of the detector system. A customized multichannel Application Specific Integrated Circuit (ASIC) with the integration of all the analog and digital components into a single chip will simplify the electronic system, decreasing the total power consumption and increasing the reliability.

CATIROC for the Small PMT System

The SPMTs are expected to detect about 50 PE per event at 1 meV spread over 25,000 PMTs, working thus in photon counting regime with a time resolution within a few ns, typical of the PMTs. For the installation, the SPMTs will be connected in groups of 128 to an autonomous front-end electronics located in underwater boxes near the SPMTs. This is possible thanks to the integration of 8 multichannel ASIC CATIROC in each readout board. The CATIROC processes the analog signals up to digitization and sends out only zero-suppressed digital data to the central processing and storage unit.

CATIROC has been designed in AMS SiGe 0.35 lm technology and integrates 16 identical channels to provide charge and time information [START_REF] Conforti | Performance of CATIROC: ASIC for smart readout of large photomultiplier arrays[END_REF].

In each channel a trigger path allows to auto-trigger on the single photo-electron thanks to a fast shaper (5 ns) followed by a low offset discriminator with threshold sets by an internal 10-bit DAC common to the 16 channels.

A charge path, made by a preamplifier, a slow shaper, a switched capacitor array and an internal 10-bit Wilkinson ADC, provides a charge measurement over a dynamic range from 160 fC (1PE, assuming a PMT gain of 10 6 )u pt o7 0p C( *400PE).

The time measurement is obtained by two paths: a "time stamp″ performed by a 26bit counter at 40 MHz and a "fine time″ obtained thanks to a TDC ramp per channel converted by another 10-bit Wilkinson ADC.

Measurements

CATIROC has been tested in the laboratory with a dedicated test board [START_REF] Conforti | Performance of CATIROC: ASIC for smart readout of large photomultiplier arrays[END_REF] and the measurements have been performed with a pulse generator to simulate a PMT input charge. Preliminary measurements with a 3″ PMT have been performed.

A first information is the detection efficiency of the single-PE signal. It is measured scanning the discriminator threshold at a given injected charge (up to 2 PE = 320 fC) and monitoring the discriminator response. Figure 1 (left) shows the trigger efficiency for given injected charges as a function of the threshold. The 50% trigger efficiency as a function of the input charge is shown in the same figure (right panel). These measurements show a trigger channel sensitivity of about 100 DACu/PE (i.e., a DAC resolution of 0.6 DACu/fC) and a noise (r) of 3.5 DACu (5.6 fC) fitting the pedestal curve (black curve on Fig. 1,left). The minimum threshold can be calculated from the baseline mean value including 5r noise (Fig. 1 right). Considering the noise measurement of 3.5 DACu, there is a very comfortable range to set the auto-triggering at a fraction of photo-electron (usually 1/4th to 1/3rd).

The SPMT system will collect typically single-PE up to a few PE's (so a good charge resolution for the single PE detection is mandatory). The charge distribution for various input signals (from 1 to 10 PE equivalent) are shown in Fig. 2 (left). The sensitivity is 16 ADCu/PE and the noise is nicely gaussian with a RMS of 1.5 ADCu (15 fC). Another crucial feature is the time resolution of the ASIC which is required to be smaller than 1 ns, such that the electronics resolution is negligible compared to that of the PMT's. The ASIC provides the signal "time of arrival″ operating in self-triggered mode. The TDC ramp has been reconstructed and is displayed in Fig. 2

(right).

A periodic pulse signal is injected in one channel and delayed by steps of 100 ps. linear fit provides the slope which gives a LSB (or TDCu) of: LSB = 1/slope = 27 ps/TDCu. The residuals are within ±15 TDCu, corresponding to ±450 ps, with an

3

RMS value of 167 ps. The residuals exhibit a periodical shape due to a coupling of the 160 MHz clock, most likely through the substrate.

The performances of CATIROC are also evaluated (very preliminary test) with signal from the PMT planned to be used for the JUNO SPMT system (3″ HZC PMT). The ASIC test board is connected to the PMT placed in a light-tight box. The dedicated SPMT acquisition code developed for JUNO is used to collect the CATIROC output data (Fig. 3 left). An example of the signal spectrum measured by the ASIC for two channels is shown in Fig. 3 right, with a clear evidence of the single-photoelectron peak. The PMT high voltage is to yield *106 gain. This measurement indicates that the ASIC has the ability to detect a single photoelectron with a charge resolution of 30%. The two channel distribution are very similar. The wiggles observed in the curves is due to a digitization artefact caused by the ASIC clock coupling. Their impact on the determination of the single-PE position and resolution has been evaluated with Monte Carlo simulations and found to be negligible for JUNO. Further testing is ongoing for full characterization of the performance of the CATIROC with JUNO PMT's.

Conclusion

The JUNO experiment is the largest liquid scintillator antineutrino detector ever built, currently under construction in the south of China. A double calorimetry system will be used for the first time ever combining about 17k 20″ PMTs (Large PMTs system) and around 25k 3″ PMTs (Small PMTs system). The ASIC CATIROC has been tested and evaluated against the requirements of the JUNO SPMT system. The results show that CATIROC fulfils the JUNO requirements. Preliminary tests with a JUNO PMT have been performed to measure the single-PE with CATIROC. In the near future, CATIROC will be installed on the first prototype of the front-end board to study the performances in real conditions.

Fig. 1 .

 1 Fig. 1. Trigger efficiency at a given injected charge as a function of the threshold (left) and the 50% trigger efficiency as a function of the input charge up to 2 PE (right).

Fig. 2 .

 2 Fig. 2. Charge measurements with the full chain for different input charges (160 fC to 1.6 pC) (left). TDC ramp reconstruction for one channel by a pulse generator signal delayed by step of 100 ps (right).

Fig. 3 .

 3 Fig. 3. Test bench for PMT measurements. The PMT is placed in a dark box, connected to an high voltage and to the CATIROC ASIC (left). Single photoelectron spectrum, in dark noise configuration, measured by the ASIC (right)