Marc Diedisheim

Christine Poitou

Laurent Genser

Chloé Amouyal

Jean-Luc Bouillot

Cécile Ciangura

MD Jean-Michel Oppert

Karine Clément

Dr Judith Aron-Wisnewsky

Cecile Ciangura

Weight Loss After Sleeve Gastrectomy: Does Type 2 Diabetes Status Impact Weight and Body Composition Trajectories?

Keywords: bariatric surgery, obesity, sleeve gastrectomy, weight-loss, Type 2 diabetes, body composition

Although bariatric surgery (BS) generally induces important and sustained weight-loss (1), the amount and trajectories of weight reduction display major inter-individual variability [START_REF] Courcoulas | Seven-Year Weight Trajectories and Health Outcomes in the Longitudinal Assessment of Bariatric Surgery (LABS) Study[END_REF][START_REF] Peterli | Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss in Patients With Morbid Obesity: The SM-BOSS Randomized Clinical Trial[END_REF].

Several reports, mostly focused on patients undergoing Roux-en-Y gastric bypass (RYGB), have identified factors involved in poorer weight-loss response. In the large US-based LABS study , with a 7 years follow-up post-RYGB, increasing age, lower baseline BMI, abnormal kidney function, smoking status and eating behavior disorders were identified as clinical parameters involved in poorer weight-loss response [START_REF] Courcoulas | Preoperative factors and 3-year weight change in the Longitudinal Assessment of Bariatric Surgery (LABS) consortium[END_REF]. Importantly, Type 2 diabetes (T2D) was the most important clinical criteria associated with lower weight-loss outcomes at 3 (5) and 7-years post-RYGB (2), concordant with results from our group obtained in independent cohorts who underwent RYGB [START_REF] Abdennour | Association of adipose tissue and liver fibrosis with tissue stiffness in morbid obesity: links with diabetes and BMI loss after gastric bypass[END_REF][START_REF] Bel Lassen | The FAT score, a Fibrosis score of Adipose Tissue: predicting weight loss outcome after gastric bypass[END_REF].

Since BS is now part of the treatment algorithm for individuals with T2D (8), both for weight reduction and glucose control improvement, one can anticipate a burst in the already high number of BS candidates. SG now represents the most performed BS type worldwide [START_REF] Angrisani | Bariatric Surgery and Endoluminal Procedures: IFSO Worldwide Survey 2014[END_REF]. To date however, no international consensus recommend a specific BS type over another in patients with T2D. In usual candidates to BS, weight-loss appears similar between SG and RYGB [START_REF] Peterli | Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss in Patients With Morbid Obesity: The SM-BOSS Randomized Clinical Trial[END_REF][START_REF] Osland | Weight Loss Outcomes in Laparoscopic Vertical Sleeve Gastrectomy (LVSG) Versus Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) Procedures: A Meta-Analysis and Systematic Review of Randomized Controlled Trials[END_REF][START_REF] Salminen | Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss at 5 Years Among Patients With Morbid Obesity: The SLEEVEPASS Randomized Clinical Trial[END_REF]. However, long-term follow-up regarding weight-loss trajectories post-SG remain scarce, and when available, are often pooled with those post-RYGB [START_REF] Aminian | Association of Metabolic Surgery With Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes and Obesity[END_REF]. Thus, it remains unclear whether T2D status negatively impacts weight-loss response post-SG as already demonstrated post-RYGB [START_REF] Courcoulas | Seven-Year Weight Trajectories and Health Outcomes in the Longitudinal Assessment of Bariatric Surgery (LABS) Study[END_REF][START_REF] Courcoulas | Preoperative factors and 3-year weight change in the Longitudinal Assessment of Bariatric Surgery (LABS) consortium[END_REF][START_REF] Bel Lassen | The FAT score, a Fibrosis score of Adipose Tissue: predicting weight loss outcome after gastric bypass[END_REF]. Furthermore, given the specific impact of adipose-tissue compartments on obesity-related metabolic complications [START_REF] Gepner | Effect of Distinct Lifestyle Interventions on Mobilization of Fat Storage Pools: CENTRAL Magnetic Resonance Imaging Randomized Controlled Trial[END_REF], rather than weight-loss per se, it could be more relevant to evaluate body-composition improvement (i.e. loss of total fat-mass (FM) and maintenance of fat-free mass (FFM)) and the reduction of the most important ectopic fat (i.e. visceral fat that can be derived from DXA-assessed trunk-fat mass). While similar body composition improvement post-RYGB and SG have already been observed [START_REF] Verger | Micronutrient and Protein Deficiencies After Gastric Bypass and Sleeve Gastrectomy: a 1-year Follow-up[END_REF], the effect of T2D status on these changes has not yet been studied. Therefore, we aimed to compare the effects of SG in severely obese patients with and without T2D on weight-loss trajectories and changes in selected body composition indicators to assess SG-induced beneficial outcomes in individuals with T2D.

Research Design and Methods

Study design and participants

Using our prospective BS cohort ("BARICAN" recorded in CNIL n°1222666), followed at the Nutrition department of Pitié-Salpêtrière university hospital (Paris, France) and meeting with BS guidelines [START_REF] Liu | Accumulation and Changes in Composition of Collagens in Subcutaneous Adipose Tissue After Bariatric Surgery[END_REF], we retrospectively selected all patients who underwent SG, with complete follow-up data set at one year post-SG. We solely selected patients with a primary SG intervention, since revision surgery performs worse in terms of weight-loss outcomes than primary intervention [START_REF] Thereaux | Five-year weight loss in primary gastric bypass and revisional gastric bypass for failed adjustable gastric banding: results of a case-matched study[END_REF][START_REF] Wijngaarden | Impact of initial response of laparoscopic adjustable gastric banding on outcomes of revisional laparoscopic Roux-en-Y gastric bypass for morbid obesity[END_REF][START_REF] Dardamanis | A Retrospective Comparative Study of Primary Versus Revisional Roux-en-Y Gastric Bypass: Long-Term Results[END_REF]. Following both national and international guidelines [START_REF] Mechanick | Clinical Practice Guidelines for the Perioperative Nutrition, Metabolic, and Nonsurgical Support of Patients Undergoing Bariatric Procedures -2019 Update: Cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, The Obesity Society, American Society for Metabolic and Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists[END_REF], preparation to surgery and post-operative follow-up were performed in a standardized manner [START_REF] Vignot | The care pathway in weight loss surgery[END_REF], , by our multidisciplinary team. In line with national guidelines [START_REF] Mechanick | Clinical Practice Guidelines for the Perioperative Nutrition, Metabolic, and Nonsurgical Support of Patients Undergoing Bariatric Procedures -2019 Update: Cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, The Obesity Society, American Society for Metabolic and Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists[END_REF], glucose control was optimized prior to surgery (i.e. more frequent outpatient visits or if needed short hospitalization just before the intervention),. SG surgical technic was performed in a standardized manner by all the surgeons in the team [START_REF] Thereaux | Comparison of results after one year between sleeve gastrectomy and gastric bypass in patients with BMI ≥ 50 kg/m 2[END_REF]. Ethical approval was obtained from the French Research Ethics Committee of CPP Ile de France-1 N°13533, and by Commission nationale de l'informatique et des libertés No. 1222666.

Bio-clinical and anthropological parameters

Anthropometric variables and patient's medical history and their related treatments (i.e. hypertension, obstructive sleep apnea, dyslipidemia, cardiovascular diseases, joint diseases, stable depression, and other systemic diseases unrelated to obesity) were collected at baseline, 1year post-BS and until the last follow-up visit (mean 2.7 years, median 2 years, interquartile 2-3).

We calculated the Framingham score at baseline. After surgery, we gathered patient's complications which are detailed in supplemental material Before surgery and during follow-up visits, blood samples were collected after a 12-hour overnight fast. Body composition by wholebody, dual-energy X-ray absorptiometry scan (DXA, Hologic Discovery W) was performed to assess fat-free (FFM), fat (FM) and trunk-fat mass, as described [START_REF] Verger | Micronutrient and Protein Deficiencies After Gastric Bypass and Sleeve Gastrectomy: a 1-year Follow-up[END_REF]. Body regions of interest (i.e. trunk) were delineated with the use of specific anatomical landmarks [START_REF] Verger | Micronutrient and Protein Deficiencies After Gastric Bypass and Sleeve Gastrectomy: a 1-year Follow-up[END_REF]. For all patients, right-side half-body scans were carried out from which whole-body composition was subsequently extrapolated [START_REF] Oppert | Resistance Training and Protein Supplementation Increase Strength After Bariatric Surgery: A Randomized Controlled Trial[END_REF]. Percent body fat was defined by (total fat mass (kg)/body weight (kg) x 100). Percent android-fat mass was defined by (trunk-fat mass (kg)/total fat mass (kg)) x 100.

Statistical analyses

Data are expressed as mean±SD for continuous variables and n (%) for categorical variables.

Changes in android FM proportion was calculated as follows: 100*[(percent android FM at 1year post-BS)-(baseline percent android FM)]/(baseline percent android FM). As data were not normally distributed, differences between groups were assessed using non-parametric tests, namely Mann-Whitney U test for non-paired analyses and Wilcoxon test for analysis of paired data. For comparisons of three or more groups, Kruskal-Wallis ANOVA was used followed by Dunn's method for post-hoc comparisons with Bonferroni correction. Categorical and binary variables were tested by the two-tailed Pearson chi-square test or Fisher exact test accordingly.

For analysis of covariance (ANCOVA), dependent and explanatory variables are detailed for each analysis; we checked that 95% of the residuals were in the interval [-1.96, 1.96] (minimal 94%). We used a longitudinal growth mixture model, which enables to group patients according to their similar weight trajectory during their 4 years post-SG follow-up. Odd ratio (OR) and 95% CI was calculated to assess strength of association between diabetes status and weight reduction age, sex, BMI and pre-surgery obesity comorbidities (hypertension, OSA and dyslipidemia. Statistical significance was set at p<0.05.

Analyses were carried out using SigmaStat ® 3.5 (Systat Software, San Jose, CA, 8 USA), XLSTAT 2016 (Addinsoft, Brooklyn, NY) and R Software 3.6.0 (www.r-project.org). Growth mixture modeling was conducted using SAS software (PROC GLM, SAS Institute 2003) with Traj plug-in according to authors' recommendations [START_REF] Jones Bl | A SAS Procedure Based on Mixture Models for Estimating Developmental Trajectories[END_REF].

Results

Baseline characteristics according to T2D status

At baseline, compared to patients without T2D (N=221), those with T2D (N=152, 40%) were significantly older, more frequently males and displayed higher prevalence of obesityrelated diseases such as obstructive sleep apnea (OSA), high blood pressure (HBP), dyslipidemia and cardiovascular diseases subsequently leading to a higher Framingham 10-year cardiovascular risk score (Table1). Despite comparable BMI, patients with T2D displayed lower percent total body-fat, but higher android-fat mass (%).

Weight-loss trajectories and body composition changes according to T2D status

Weight-loss profile, starting from 3 months (3M) post-SG, significantly differed in patients with or without T2D (Figure 1A). Weight-loss expressed as % from baseline was significantly lower in patients with T2D at 1-y (21 % vs. 27 %, p<10-3 ). Despite major inter-individual variability in both groups, patients with T2D showed a significantly worse weight-loss profile during the 1rst-year when compared to subjects without T2D (p<10 -3 Kolmogorov-Smirnov test) (Figure 1B). Importantly, weight-loss at 2 years also significantly differed according to T2D status (20% vs 26% in individuals with vs. without T2D respectively p<0.0001).In the whole cohort during the complete follow-up, 5 profiles of weight-loss response were identified using a longitudinal growth mixture model (Figure 1C) in agreement with [START_REF] Courcoulas | Weight change and health outcomes at 3 years after bariatric surgery among individuals with severe obesity[END_REF]. "Very goodresponders" (14%), "good-responders" (36%), "mild-responders" (34%) and "poorresponders" (13%) respectively lost 40%, 30%, 20% and 10% of their initial body weight. Most patients categorized as "poor-responders" regained weight after the second year of follow-up (Figure 1C). Finally, 2% were considered as a failure to SG since after a moderate weight-loss, they exceeded their pre-surgery weight during the follow-up (Group 1, Figure 1C). In accordance to our initial results, when comparing patients with weight-loss>30% (thereafter called "good responders") to those with weight-loss<20% (thereafter termed "poor responders"), we observed an increased prevalence of individuals with T2D in the "poor responders" group (52% vs. 29% p<10 -3 Figure 1D). (). T2D remained significantly associated with poorer weight response after adjustment for age, sex, BMI and pre-surgery obesity-related comorbidities (hypertension, OSA, dyslipidemia and CVD) (Odd-Ratio=1.9 [1.1 -3.2] p=0.01). Interestingly, weight regain after the first year was not significantly different according to T2D status. 17% of individuals with T2D regained at least 5% as compared to 12% of patients without T2D (p=0.379). Similarly, 6% of patients with T2D regained at least 10% as compared to 1% of patients without T2D (p=0.085).

Concerning body composition, FFM decreased significantly at 3M and remained stable until 12M, displaying a similar pattern in obese individuals with or without T2D (Figure 1E). By contrast, FM reduction, expressed as % change from baseline in FM (kg), was significantly lower in patients with vs. without T2D (Figure 1F) as early as 3M (-19 vs -16% respectively, p<0.05). This difference was further exacerbated during the follow-up (-24 vs -29% (p<10 -2 ) and -28 vs. -37% (p<10 -3 ) at 6 and 12 months, respectively).

Influence of glucose control on weight-loss outcomes and body composition changes

Weight-loss at 1-year was negatively correlated with baseline HbA1c (r=-0.24, p<10 -2 ). Furthermore, weight-loss was lower in patients with T2D above the glycemic target (HbA1c>7%) before surgery (Figure 2A) as compared to those below the target or to individuals without T2D, pointing at the negative impact of both T2D status and adverse glycemic control, despite similar BMI and FFM at baseline (Supplemental Figure 1A andB). Interestingly, glucose control also strongly influenced the amount of FM loss. It indeed deteriorated from patients without T2D to patients with T2D below or above the baseline target of 7% at both 6 and 12 months (p<10 -3 , Figure 2B). The difference remained significant after adjustment for age, sex and baseline %FFM. Noteworthy, compared to patients with Hba1c<7%, those above 7% displayed more severe T2D. Indeed, they displayed increased T2D duration (9.3±7.6 vs. 4.9±5 years, p<0.0001), increased number of glucose-lowering drugs (2.1±1.1 vs. 1.2±1, p<0.0001) at baseline and finally increased prevalence of insulin-therapy requirement at baseline (53% vs. 11%, p<0.0001) and at 1-year (29% vs. 1%). T2D duration was not associated with weight-loss outcomes (p=0.84).

Due to baseline differences in adiposity and lower FM-loss in patients with T2D, both groups displayed similar body composition at 12M post-SG (Figure 2C), thus suggesting worse body composition improvement 1-year post-SG in individuals with T2D. Android FM also displayed significantly different reduction profiles in patients with or without T2D (65% to 64% vs. 60% to 57% respectively from baseline to 12 months p=0.001; Figure 2D). These differences remained significant between groups after adjustment for age, sex and baseline FFM.

Other surgical outcomes

Despite poorer weight-loss, T2D individuals largely benefited from SG as seen with a 52% rate of diabetes remission at one year in our cohort. Furthermore, we did not evidence any differences in surgical adverse effects post-SG according to T2D status (Supplementary results and figure 2S)

Discussion

We herein show in a French BS cohort that both T2D status and poor pre-surgery glycemic control negatively impacts weight-loss and body composition changes post-SG. Compared to patients without T2D, individuals with T2D displayed lower improvement of their body composition, abdominal adipose tissue repartition and weight-loss. This was exacerbated in individuals with poorer glucose control. Nevertheless, post-surgery complication rate was similar in both groups. These results point at the importance of a strict glucose control before surgery not only to reduce hyperglycemia-related surgical complications [START_REF] Rometo | Perioperative Glycemic Management of Patients Undergoing Bariatric Surgery[END_REF] but also to optimize weight-loss.. We herein confirm that the amount of weight-loss and its trajectories post-SG display high variability, in agreement with other weight-loss interventions such as dietary interventions [START_REF] Batterham | Baseline characteristics associated with different BMI trajectories in weight loss trials: a case for better targeting of interventions[END_REF], adjustable gastric banding and RYGB [START_REF] Courcoulas | Seven-Year Weight Trajectories and Health Outcomes in the Longitudinal Assessment of Bariatric Surgery (LABS) Study[END_REF][START_REF] Sjöström | Bariatric surgery and long-term cardiovascular events[END_REF]. Importantly, although the impact of T2D status on weight-loss post-SG had never been properly evaluated, previous research seemed in line with our current findings. Indeed, in two recent RCTs comparing SG and RYGB, the % excess weight-loss at 5 years post-SG reached 61% in one and 49% in the second study. Differences in weight-loss outcome could originate from the 2-fold higher percentage of T2D individuals included at baseline in the first study [START_REF] Salminen | Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss at 5 Years Among Patients With Morbid Obesity: The SLEEVEPASS Randomized Clinical Trial[END_REF] (i.e. 43 vs. 24% in the first vs. the second study, respectively) [START_REF] Peterli | Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss in Patients With Morbid Obesity: The SM-BOSS Randomized Clinical Trial[END_REF][START_REF] Salminen | Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss at 5 Years Among Patients With Morbid Obesity: The SLEEVEPASS Randomized Clinical Trial[END_REF]. T2D status-associated lesser weight-loss represents an important information for routine clinical care. It is indeed critical to better acknowledge expected weightloss outcomes, on top of glycemic profile improvements [START_REF] Dicker | Long-Term Outcomes of Three Types of Bariatric Surgery on Obesity and Type 2 Diabetes Control and Remission[END_REF], especially now that BS is included in the T2D treatment algorithm [START_REF] Schauer | Clinical Outcomes of Metabolic Surgery: Efficacy of Glycemic Control, Weight Loss, and Remission of Diabetes[END_REF].

Since, pre-surgery glucose homeostasis negatively influences weight-loss even when most clinical confounding factors are taken into account, this pleads for optimizing glycemic control before BS. One could hypothesize that patients with poorer glycemic control are below their optimal weight before surgery. BS will first enable the improvement of their glucose homeostasis [START_REF] Pories | Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus[END_REF], thus subsequently limiting weight-loss. Indeed, poor glycemic control has previously been associated with increased basal metabolic rate [START_REF] Mäkimattila | Causes of weight gain during insulin therapy with and without metformin in patients with Type II diabetes mellitus[END_REF]. Furthermore, uncontrolled diabetes-related increased glycosuria is also associated with weight-loss (29,30), however glycosuria was not assessed herein. Nevertheless, while BS seems to perform lower in individual with T2D, BS has shown its superiority over intensive medical therapy in several RCTs including SG [START_REF] Schauer | Bariatric surgery versus intensive medical therapy for diabetes--3-year outcomes[END_REF][START_REF] Schauer | Bariatric Surgery versus Intensive Medical Therapy for Diabetes -5-Year Outcomes[END_REF][START_REF] Mingrone | Bariatric surgery versus conventional medical therapy for type 2 diabetes[END_REF][START_REF] Mingrone | Bariatricmetabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial[END_REF], thus pointing at the benefit for these patients to undergo BS, which present similar rates of surgical complications in individuals with or without T2D. Importantly, the choice of BS type remains open, to date. .

Our results stimulate the need to develop and evaluate add-on strategies, proposed after BS to further improve weight-outcomes in T2D patients. Some first line of evidence already supports this claim in general BS candidates. For example, adherence to Mediterranean diet postsurgery significantly improved weight-loss response at 1-year, after RYGB or SG [START_REF] Contreras | Adherence to Mediterranean Diet or Physical Activity After Bariatric Surgery and Its Effects on Weight Loss, Quality of Life, and Food Tolerance[END_REF]. However, this was not specifically tested in individuals with T2D. Likewise, exercise training programs started post-BS are able to optimize weight-loss responses [START_REF] Bellicha | Effectiveness of exercise training after bariatric surgery-a systematic literature review and meta-analysis[END_REF]: patients with high-adherence to moderate or intense physical activity post-BS displayed better weight-loss outcomes [START_REF] Fontana | Bariatric Surgery Associated with Practice of Moderate to Intense Physical Activity Related to Weight Loss, Activity Level in Daily Life, Dyspnea, and Quality of Life of Sedentary Individuals with Morbid Obesity: a Prospective Longitudinal Study[END_REF]. Addon physical activity training program after the 1 st -year post-BS also prevent weight regain [START_REF] Marc-Hernández | Effects of a High-Intensity Exercise Program on Weight Regain and Cardio-metabolic Profile after 3 Years of Bariatric Surgery: A Randomized Trial[END_REF].

Finally, the adjunction of GLP1-R agonist (compared to placebo) induces improved weight-loss in individuals who underwent BS and remained with T2D 2 years post-surgery [START_REF] Miras | Adjunctive liraglutide treatment in patients with persistent or recurrent type 2 diabetes after metabolic surgery (GRAVITAS): a randomised, double-blind, placebo-controlled trial[END_REF]. These strategies should now be further tested in T2D individuals' candidates to SG.

Importantly, body composition and fat distribution amelioration post-BS [START_REF] Verger | Micronutrient and Protein Deficiencies After Gastric Bypass and Sleeve Gastrectomy: a 1-year Follow-up[END_REF][START_REF] Keidar | Roux-en-Y gastric bypass vs sleeve gastrectomy for obese patients with type 2 diabetes: a randomised trial[END_REF], which we also herein observe, is better to predict health outcomes and mortality risk than BMI or weightloss per se [START_REF] Thibault | The evaluation of body composition: a useful tool for clinical practice[END_REF][START_REF] Heitmann | Mortality associated with body fat, fat-free mass and body mass index among 60-year-old swedish men-a 22-year follow-up. The study of men born in 1913[END_REF]. We can speculate that our observed limited reduction in visceral fat in T2D individuals could be less favorable for cardiometabolic outcomes in the long term post-SG [START_REF] Sjöström | Relationships between changes in body composition and changes in cardiovascular risk factors: the SOS Intervention Study. Swedish Obese Subjects[END_REF].

Nevertheless, despite this poorer response in individuals with T2D, most of them display major improvement in glycemic control (either engaging in diabetes remission or improving their HbA1c while reducing the number of glucose-lowering agent) [START_REF] Aminian | Individualized Metabolic Surgery Score: Procedure Selection Based on Diabetes Severity[END_REF]. Furthermore, on top of weight-loss and metabolic improvements, individuals with T2D undergoing all types of BS also reduced their T2D-related cardiovascular complications [START_REF] Romeo | Cardiovascular events after bariatric surgery in obese subjects with type 2 diabetes[END_REF] and their risks of developing macrovascular events during a 5-years follow-up, as compared to patients with T2D not undergoing BS [START_REF] Fisher | Association Between Bariatric Surgery and Macrovascular Disease Outcomes in Patients With Type 2 Diabetes and Severe Obesity[END_REF]. Although weight reduction and FM loss post-SG might be lower in individuals with T2D, a majority of them metabolically benefit from BS (44) while they could eventually benefit even more with an optimized weight-loss synergic intervention. Finally, literature has previously shown that BS enables cost reduction in T2D follow-up as compared to before surgery [START_REF] Gesquiere | Medication Cost is Significantly Reduced After Roux-en-Y Gastric Bypass in Obese Patients[END_REF] or to medical therapy alone [START_REF] Neovius | Health care use during 20 years following bariatric surgery[END_REF], again pointing at the benefit for T2D individuals to undergo BS.

In conclusion, although SG is generally efficient to induce weight reduction and improvement of obesity-related diseases, weight-loss is lower in individuals with T2D, especially in those with uncontrolled diabetes prior to the surgery. Nevertheless, these patients still benefit from overall metabolic improvement and display similar rate of surgical complications than individuals without T2D. Our work paves the way for optimization of T2D follow-up in this context.

Figure legend

Fig. 1 :

 1 Fig. 1: Weight-loss post and body composition changes sleeve gastrectomy: contribution of

Fig. 2 :

 2 Fig. 2: Weight-loss and body composition changes from baseline to one-year post-sleeve

Funding. Clinical study was sponsored by the Assistance Publique-Hôpitaux de Paris, and funding of this cohort obtained by several programs: Clinical Research contracts for clinical investigation (PHRC 02076 to KC, CRC P050318 to CP and CRC-FIBROTA to JAW and KC) and the French National Agency of Research ANR ("Investissement d'Avenir" FORCE network (F-Crin)), Metagenopolis grant ANR-11-DPBS-0001 and IHU-ICAN (reference ANR-10-IAHU-05, BARICAN research project). Acknowledgments. We thank Dr Florence Marchelli MD (NutriOmics and Human Nutrition Research Center (CRNH Ile de France) and Rohia Alili (NutriOmics and Human Nutrition Research Center (CRNH Ile de France) for their contribution to the database and biobanking and Valentine Lemoine for patient follow-up (ICAN).

Author contributions. JAW designed the study. CP, CC, JMO, KC, JAW contributed to patient recruitment and coordinated clinical investigation, patient phenotyping, and sample collection.

MD and JAW analyzed data. MD, KC and JAW wrote the manuscript. LG and JLB operated patients. MD, CP, CC, CA, JMO, KC and JAW contributed to data presentation and the manuscript.

All authors reviewed the manuscript. JAW is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Tables Table 1: Pre-surgery clinical characteristics of patients from the Barican cohort, comparing individuals with obesity with or without T2D undergoing SG.

Controls


Thanh Binh Nguyen
email: thanh-binh.nguyen@cnrs.fr

Pascal Retailleau

Umpolung Strategy for a,a'-Functionalization of Ketones with 2-Aminothiophenols: Stereoselective Access to Spirobis(1,4-Benzothiazines)

Keywords: sulfur, 1,4-benzothiazines, DMSO

    Umpolung Strategy for α,α'-Functionalization of Ketones with 2-Aminothiophenols: Stereoselective Access to Spirobis(1,4-benzothiazines) T .B. Nguyen, Pascal

1,4-Benzothiazine derivatives [1] have been reported to be present in a variety of natural products [2] and to exhibit a wide range of pharmacological properties including immunomodulating, antifungal, antirheumatic, anti-aldoso-reductase, anti-arrhythmic, vasorelaxant, anti-allergic, anti-hypertensive, neuroprotective and cytotoxic activities. [3] Figure 1. Selected useful 1,4-benzothiazine derivatives For example, antibiotic 3a designated BMY 40662 was discovered during a large scale fermentation of the anticancer agent esperamicin A1, [2a,b] whereas aplidinones A-C 3b were isolated from the Mediterranean ascidian Aplidium conicum (Figure 1). [2d] While carbamate 1,4-benzothiazine 3c displays a good antifungal activity, [4] amide 3d is an immunomodulator. [5] Compound 3e was found to be a functional dye capable of decomposing in biological systems to methylene blue and was used in diagnostics. [6] 1,4-Benzothiazine-substituted acetylene 3f could be used as models for redox-active molecular wires. [7] Interestingly, 1,4-benzothiazine derivatives 3g,h were found to exhibit either p-type or n-type semiconductivity depending on their angular or linear arrangement of the fused pentacyclic system. [8] One of the most important objectives of organic chemistry is to develop straightforward and selective access to complex molecules using simple and readily available starting materials. Such a strategy becomes more attractive, especially for large scale production if the reactions could proceed under simple conditions without using expensive reagents or catalysts. Following this direction, we have been focusing our efforts on using elemental sulfur as a versatile tool to achieve a wide range of redox transformation as either stoichiometric or catalytic component. [START_REF] Nguyen | For reviews on the organic reactions involving elemental sulfur[END_REF] The rich chemistry of elemental sulfur relies heavily on the ready scission of its S-S bonds under thermal, photochemical or catalytic conditions. In a broader extent, the study of any compounds bearing S-S bond or capable of forming this linkage during the course of the reaction could benefit from the organic chemistry of this element thanks to the facile interconversion between SH and S-S species. Herein, we disclose an unusual approach to novel spirobis(1,4benzothiazines) based on an acid-catalyzed oxidative condensation of two molecules of 2-aminothiophenols with one molecule of a,a'-enolizable ketones. The strategy meets most of the above-mentioned expectations.

We have previously reported an oxidative functionalization of cyclohexanones with 2aminophenols in DMSO catalyzed by elemental sulfur. Via this reaction, a wide range of heteropropellanes were regio-and stereoselectively formed in high yields (Scheme 1). [10] Scheme 1. Difference in reactivity between o-aminophenol A and o-aminothiophenol 1a with cyclohexanone 2a

Extrapolating from this, we wondered if the same reactivity could be observed with 2aminothiophenols. [START_REF] Sauter | For reports on reaction of cyclohexanones with 2aminothiophenols leading to benzothiazolines and phenothiazines[END_REF] For this purpose, the same reaction conditions were applied to 2-aminothiophenol 1a and cyclohexanone 2a (Scheme 1 and Table 1, entry 1).

Table 1. Screening of the reaction conditions Entry [a] Additive/catalyst (x equiv) Temp (ºC) Yield (%) [b] 1 HOAc (2)/S (0. PTSA (0.1) 80 69 8 [c] TFA (0.1) 80 65 9 [d] TFA (0.1) 60 0 10 [e] TFA (0.1) 80 71 [a] Reaction conditions: 1a (2 mmol, 250 mg), cyclohexanone (1 mmol, 98 mg), DMSO (0.3 mL, 4.5 mmol), additive or catalyst (x equiv) under an argon atmostphere. [b] Isolated yield. [c] Reaction performed in the absence of DMSO. [d] Reaction performed in N,N-dimethylacetamide (DMAc) (0.3 mL) instead of DMSO. [e] Reaction performed under air.

To our delight, a 2:1 solid adduct with a similar empirical formula was obtained. To our surprise, the X-ray crystallographic study revealed its molecular structure as a unique racemic stereoisomer with two equatorial C-S bonds issued from the sulfuration of C-1 and C-6 of 2a and the two geminal C-N bonds resulting from condensation of two amino groups with the carbonyl function. Further optimization of the reaction conditions proved that neither sulfur nor acetic acid was essential to the formation of 3aa (entries 2-4).

Scheme 2. Reaction scope More strikingly, we subsequently found that the reaction could be performed in better yields in the presence of TFA or PTSA as a strong acid catalyst (entries 5-7). When DMSO was replaced by a dipolar aprotic solvent such as DMAc, only trace of 3aa was formed, suggesting the essential role of DMSO (entry 8). The reaction was found also to stagnate at temperature as low as 60 ºC (entry 9). Additionally, no significant difference was observed if the reaction was performed under air or an inert atmosphere (entries 10 vs 6). With this set of optimized conditions in hand (entry 10), we went on to investigate the scope of the reaction. Similar reactivity was observed with 2-amino-4chlorothiophenol 2b, leading to high yield of spiro compound 3ba. To confirm the regiochemistry, the reaction with three 4-substituted cyclohexanones 2b-d were evaluated (Scheme 2).

To our delight, in all cases, the reactions resulted in the products as expected regioisomers 3ab, 3ac and 3ad. More interestingly, only one stereoisomer was formed. X-ray structural analyses showed that two newly formed C-S bonds and the existing C-C bond between the cyclohexane ring and the 4-substituent were all equatorial. The reaction conditions were next applied to 3,3-and 4,4-dimethylcyclohexanones 2e-f. In both cases, the products were obtained as single isomers with two equatorial C-S bonds. On the other hand, the reaction of 3,3,5-trimethylcyclohexanone 2g with 1a resulted in a 2:1 mixture of two isomers 3ag.

At this stage, we were eager to extend our method to other cycloalkanones. Gratifyingly, the reaction with cycloheptanone 2h and cyclooctanone 2i gave the major products 3ah and 3bi with the same stereochemistry, i.e. two newly formed C-S bonds are in a cis geometry. A better reactivity was observed with cyclooctanone than with cycloheptanone.

The ratio of these isomer and the other minor ones were found to be 4:1 and 3:1 for cycloheptanone 2h and cyclooctanone 2i, respectively. In opposition, the reaction of cyclododecanone provided the C2 symmetric product 3aj, The structure of which was determined once again by X-ray. The presence of another minor isomer 3aj' was also detected by 1 H NMR (3aj:3aj' ratio 13:1). Upon leaving the solution in CDCl3 of the freshly isolated in an NMR tube at rt, the major isomer 3aj was found to convert to the minor isomer 3aj' and an equilibrium was attained with a new ratio 3aj:3aj' 5:1. It was possible that this isomerization proceeded via ring opening-ring closing mechanism as suggested in Scheme 3. The difference in stereochemistry outcome between six-to-eight membered cycloalkanones and cyclododecanone could be explained based on ring constraints (vide infra). We investigated further the chemical behavior of open chain ketones. [START_REF]Reaction of 2-aminothiophenols with acetone or higher homologues were previously reported to yield benzothiazolines or imines[END_REF] Scheme 3.

As the simplest member of this series, acetone reacted without any surprise, leading to C2 symmetric product 3al in a low yield, possibly due to its low boiling point (bp 56 ºC) whereas the reaction was performed at 80 ºC. In the case of diethyl ketone, product 3am was formed along with a minor epimer at the gem N,N-disubstituted carbon 3am' in a 1.4:1 ratio. Since both 3am and 3am' were C2-symmetric, their 1 H and [START_REF]This product was reportedly prepared by heating dimedone 5 with 1[END_REF] C NMR spectra corresponded to half of the molecule (see Supporting Information).

The relative configuration of 3am determined by Xray crystallography was shown to be the same as that of cyclododecanone. This similarity suggested that the twelve-membered ring ketone substrate behaved in the same manner as an open chain dialkyl ketone. Subsequently, non-symmetrical ketones were tested. Isopropyl methyl ketone 2n and cyclobutyl methyl ketone 2o were found to react efficiently, providing the corresponding spiro product in good to excellent yields. The dispiro structure of 3ao was verified by X-ray structural determination.

Our conditions however failed with 4-heptanone, diisopropyl ketone and cyclopropyl methyl ketone. This can be explained by steric hindrance for the two first cases and ring constraint for the third case.

Finally, we applied our conditions to dimedone 5. In this case, regardless excess use of 1a (up to 4 equiv), the corresponding 1:1 adduct 6 [START_REF]This product was reportedly prepared by heating dimedone 5 with 1[END_REF] was formed exclusively as orange solid in high yields, even at rt temperature. The result of the reaction involving equimolar amounts of both starting materials was summarized in Scheme 4.

Scheme 4. Reaction with 1,3-dicarbonyl compounds 5a-c

To gain a mechanistic insight into these oxidative C-S bond formation reactions, some control experiments were carried out (Scheme 5). First, 2aminothiophenols 1a was found to readily undergo oxidative dimerization to disulfide 4a upon heating with DMSO in the presence or even in the absence of TFA catalyst (eq. 1).

Second, heating an equimolar mixture of 1a and 2a with TFA catalyst in the absence of DMSO yielded only in benzothiazoline 5a as a result of a non-redox condensation. Third, when disulfide 4a was used in place of 2-aminothiophenol 1a under the standard conditions, spiro 3aa was formed in a comparable yield. [START_REF]3aa was described to be formed in low yield along with disulfa analog of B from the reaction of cyclohexanone 2a with disulfide 4a. In this case, since DMSO was not used and the reaction was performed under an inert atmosphere, only a half of disulfide 4a could act as the[END_REF] On the basis of previous reports and our results, a proposed reaction mechanism is shown in Schemes 6 and 7. Two different reaction pathways are hypothesized for the formation of spiro compounds derived from either cyclohexanone 2a (Scheme 6) or diethyl ketone 2m (Scheme 7).

As demonstrated in eq 1. Scheme 5, since 2aminothiophenol 1a is readily oxidized into dimer 4a, the nucleophilicity of the thiol group in 1a is masked and replaced by electrophilicity of disulfide linkage in 4a. In another word, the sulfur atom was subjected to a polarity inversion or umpolung by oxidation promoted by DMSO. [START_REF] Sorabad | For an example of oxidation of benzenethiol into diphenyl disulfide by DMSO in the presence of HBr as a strong acid[END_REF] Scheme 5. Control experiments Consequently, a similar reactivity as for 2aminophenol A to form disulfa analog of heteropropellane B (Scheme 2) could not be observed. The reaction was initiated by an acid-catalyzed condensation of cyclohexanone 1a and aniline 4a to form imine C, which underwent an electrophilic sulfurative cyclization into tetrahydrophenothiazine E via enamine D (Scheme 6). Enamine F issued from imine D could experience another electrophilic sulfurative with disulfide 4a to generate cis-G. Although the isomer trans-G could be initially formed, it could undergo an acid-catalyzed isomerization into cis-G which is thermodynamically more stable. Final acid-catalyzed cyclization of cis-G would provide 3aa. It should be noted that attack from either upper or lower side would result in the products with the same relative configuration. Scheme 6. Proposed reaction pathway for cyclohexanone

In the cases of acyclic ketones or large ring such as cyclododecanone, the initial steps of formation of 1:1 adduct proceeded in the same manner to give Zenamine F' and its E-isomer F'' (Scheme 7).

Scheme 7. Proposed reaction pathway for diethyl ketone

While the E-configuration of the double bond of enamine F is determined by the ring constraint for sixmembered ring, in the present cases, Z-enamine F' is more stable than its E isomer F''. Subsequent oxidative sulfuration of F' with 4a via lower face attack would lead to G' which finally cyclized to spiro compounds 3am and 3am'. It should be noted that while both Ssubstituted chiral carbons are configurationally relatively stable, the configuration of gem N,Ndisubstituted carbon is much more flexible. 3am and 3am' are thus interconvertible.

In conclusion, we have explored an umpolung reactivity of 2-aminothiophenols in the a,a'functionalization of ketones. A wide range of acyclic and alicyclic ketones could be used as carbonyl substrates, leading to the corresponding spirobis(1,4benzothiazines) in moderate to good yields and excellent stereoselectivity in most cases. More strikingly, the reaction required only TFA as an acid catalyst and DMSO as oxidant. The stereochemical outcome was found to be strongly controlled by ring constraint. The results presented here confirm once again the fact that complex structures could be achieved from simple starting materials under simple reaction conditions. Further experiments on the mechanism as well as synthetic application are currently ongoing in our laboratory.

Experimental Section

A mixture of 2-aminothiophenol 1 (2 mmol), ketone 2 (1 mmol), TFA (0.1 mmol, 10 mg) in DMSO (4 mmol, 0.3 mL) was stirred in a 7-mL tube closed with a rubber septum equipped with a deflated rubber balloon at 70 ºC for 16 h. After being cooled to room temperature, the crude reaction mixture was purified as indicated for each compound, by trituration with methanol or column chromatography on silica gel column (eluent heptane:EtOAc 99:1 to 95:5). For experimental details, full characterization, and copies of NMR spectra of all compounds, see Supporting Information.

CCDC 2005793-2005801 contain the supplementary crystallographic data for 3ai, 3am, 3ao, 3aa, 3ae, 3ac, 3ad, 3ah, 3aj respectively in this paper. These data can be

Acknowledgements

We thank Pr. Akiyama Takahiko, Department of Chemistry, Gakushuin University, Tokyo, Japan for a fruitful discussion on the chemistry of 2-aminothiophenols.

Data Centre via www.ccdc.cam.ac.uk/data_request/cif.


Eric Duverger

Anne-Gaëlle Boyer

Hélène Sauriat-Dorizon

Philippe Sonnet

Régis Stephan

Marie-Christine Hanf

Damien Riedel
email: damien.riedel@u-psud.fr

Two-Dimensional Functionalized Ultrathin Semi-Insulating CaF2 Layer on the Si(100) Surface at a Low Temperature for Molecular Electronic Decoupling

Keywords: 2D materials, insulating layer, CaF2, Silicon, electronic decoupling

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

INTRODUCTION

The growth control, as well as the properties of electronic insulating layers, on various materials surfaces is of key importance for many domains, not only including electronic devices 1 . This topic has thus been the object of a large amount of fundamental 2 and applied investigations [START_REF] Celler | Frontiers of silicon-on-insulator[END_REF] . It is still impacting various research fields targeting both applied and fundamental physics in which flexible opto-electronic devices [START_REF] Forrest | The path to ubiquitous and low-cost organic electronic appliances on plastic[END_REF][START_REF] Mur | Ultrathin oxides grown on Si(100) by rapid thermal oxidation for CMOS and advanced devices[END_REF][START_REF] Gad | Improved Si/SiOx interface passivation by ultra-thin tunneling oxide layers prepared by rapid thermal oxidation[END_REF] , sensors [START_REF] Klaas | Component Integrated Sensors: Deposition of Thin Insulation Layers on Functional Surfaces[END_REF][START_REF] Ludwig | Sub-femtosecond electron transport in a nanoscale gap[END_REF] or biological functions are still feeding new paradigms [START_REF] Mishra | Protein kinase C and calcineurin cooperatively mediate cell survival under compressive mechanical stress[END_REF][START_REF] Mabeck | Chemical and biological sensors based on organic thin-film transistors[END_REF] .

In many research fields, the growth of mesoscopic devices having relatively thick dielectric layers made for example of SiO2 on semiconductors or Al2O3 on metals surfaces (MS) often reach wideness of few nanometers. This renders their fabrication seldom repeatable at the atomic scale and may well also present conducting leaks [START_REF] Miranda | Soft Breakdown in Ultrathin SiO2 Layers: the Conduction Problem from a New Point of View[END_REF] .

At lower scale, the approach is different since current leakage can be exploited for specific tunnel transport in molecular scale devices [START_REF] Yengui | A two-dimensional ON/OFF switching device based on anisotropic interactions of atomic quantum dots on Si(100)[END_REF][START_REF] Kolmer | Electronic transport in planar atomic-scale structures measured by two-probe scanning tunneling spectroscopy[END_REF] . In the context of molecular electronics, ultra-thin insulating layers made of a few atomic crystallographic scale coats have already been largely investigated. Several well-known materials such as NaCl [START_REF] Repp | Imaging Bond Formation between a Gold Atom and Pentacene on an Insulating Surface[END_REF] as well as Al2O3 15 , 16 have demonstrated efficient electronic decoupling properties of single atoms or molecules on Cu, Au or Ag surfaces. However, on metal surfaces, few layers of dielectric material are necessary to reach electronic insulating properties with surface energy gaps reaching ~ 3 eV. Hence, at this scale, the scanning probes techniques allow investigating ways to tune their electrical insulating properties, in particular for the study of photonics or electronic devices [START_REF] Rafael | Single-molecule resonnance Raman effect in plasmonic nanocavity[END_REF] .

Yet, on semiconductor surfaces, except for SiO2 dielectric, the growth control of ultrathin semiinsulating layers remains barely studied and therefore faintly understood, especially at atomic scale thickness. This arises mainly because of the anisotropy of semiconductor surfaces reconstructions that may prevent a good 2D lattice matching with the electronic insulating material. Additional surface passivation techniques, e.g. with elements like hydrogen [START_REF]On-Surfaces Atomic Wires and Logic Gates[END_REF] or via the use of molecular layers 19 have also been explored but the obtained surface band gap energy is often reduced to 1-2 eV.

As the development of active devices at smaller scales remains a quest in many domains including molecular electronic [START_REF] Ramos | Probing charge transfer dynamics in a single iron tetraphenylporphyrin dyad adsorbed on an insulating surface[END_REF] or nanoscale magnetism [START_REF]Ultrathin films, multilayers and Nanostructures[END_REF] for which a thorough control of the atomic scale environment is decisive, it is particularly vital to determine the atomic and electronic structures of a semi-insulating layer able to support a molecular or atomic assembly.

To the best of our knowledge, ultrathin insulating layers using CaF2 is the sole alternative to reach efficient electronically insulating properties of semiconductor surfaces. It offers a clear alternative to NaCl layers on metal surfaces. Alkaline earth fluorides such as BaF2 or SrF2 have also been explored as candidates on silicon surfaces but with reduced insulating efficiencies [START_REF] Sumiya | Scanning tunneling microscopy study of initial growth of CaF2 and BaF2 on Si(111)[END_REF] . On Si(111) surfaces, the structure of the ultrathin CaF2 reconstruction has been often investigated and exhibits a relatively weak surface gap of ~1.7 eV [START_REF] Klust | Electronic structure evolution during the growth of ultrathin insulator films on semiconductors: From interface formation to bulk-like CaF2 ∕ Si(111) films[END_REF][START_REF] Lucas | Structural transition of the CaF2/Si(111) interface[END_REF][START_REF] Vexler | Degradation effects in the one-band-tunneling Au/CaF2/n-Si(111) MIS structures[END_REF] and is still an attractive candidate for mesoscopic MISFET (Metal Insulator Semiconductor Field Transistors) structures [START_REF] Illarionov | Ultrathin Calcium fluoride insulators for two-dimensional field-effect transistors[END_REF] . At smaller scale, the epitaxial growth of CaF2 on Si(100) surfaces exhibits ultrathin insulating anisotropic reconstructions forming ribbons of stripes that offer additional functionalities for organizing adsorbates [START_REF] Chiaravalotti | Atomic scale control of hexaphenyl molecules manipulation along functionalized ultra-thin insulating layer on the Si(100) surface at low temperature (9 K)[END_REF] . While the electronic structure of the CaF2/Si(100) has been investigated with mesoscopic techniques [START_REF] Pasquali | Calcium fluoride on Si(001): Adsorption mechanisms and epitaxial growth modes[END_REF] , it is of crucial importance for the understanding of their electronic structure to investigate their atomic scale formation [START_REF] Chiaravalloti | Atomic-scale study of the adsorption of calcium fluoride on Si(100) at low-coverage regime[END_REF] . Yet, a detailed and complete description of the precise atomic and electronic structure of ultrathin CaF2 insulating ribbons of stripes on Si(100) is lacking, as well as the characterization of the interaction of this type of semi-insulating layer with molecular adsorbates.

In this article, we investigate experimentally and theoretically the atomic scale structure of CaF2 ribbons of stripes resulting of the growth of ~ 1.3 monolayer of CaF2 on the bare Si(100) surface. The scanning tunneling microscope (STM) topographies and spectroscopic measurements obtained at 9 K provide a precise picture of the stripes structures. As well, it provides the relative positioning of the ribbons with respect to the silicon dimer rows and the ensuing wetting layer (WL) that is initially on the bare silicon. Our investigations also provide a complete characteristic of the electronic insulating properties via an estimation of the CaF2 layer surface gap energy. The surface gap is considered here as different from the bulk gap energy and defined as the energy difference between the upper part of the valence band and the lower part of the conduction band for the first atomic layers of the surface, as previously studied [START_REF] Yengui | Atomic scale study of corrugating and anticorrugating states on the bare Si(100) surface[END_REF] . In order to determine precisely the atomic structure of the stripes and confirm our experimental findings, we have used the density functional theory (DFT) with annealing procedure and calculated STM images. Additionally, the DFT-Hubbard method is used to provide additional insights on its electronic structure and allows to estimate the surface energy gap with the projected density of state (PDOS) information. Finally, in order to estimate the quality of the electronic decoupling, we use STM analysis combined with van der Waals functionals within DFT method to describe the interactions of a single iron-tetraphenylporphyrin (FeTPP) molecule with a ribbon of CaF2 stripe. The ensemble of our results indicates that this two-dimensional electronic insulating material allows a strong electronic decoupling of organic or inorganic adsorbates.

EXPERIMENTAL SECTION

2.1. Synthesis and epitaxial preparation of the CaF2/Si(100) surfaces.

The characterization of the ultrathin insulating layer is performed with a low temperature (9 K)

PanScan STM head from CREATEC. The Si(100) samples (n-doped (As), ρ = 5cm) are cleaned in ultra-high vacuum using repetitive annealing cycles consisting of a rapid temperature increasing up to 1100 °C followed by a slow temperature ramp down to 600 °C. The reconstructed Si(100) surface is then exposed to a flux of CaF2 molecules evaporated from an effusion cell, previously calibrated with a quartz balance, heated at 1065 °C, while the Si sample is kept at a temperature of 720 °C. The CaF2 exposure, lasts for 120 s for a total coverage of 1.3 monolayers. During the CaF2 exposure the pressure in the preparation chamber is kept below 2 x 10 -10 torr. Following this procedure, the sample is cooled down to 12K and introduced in the STM chamber for analysis. Note that the phase diagram of the CaF2 epitaxy on the Si(100)-2x1 is noticeably different than the one for the Si(111)-7x7 reconstruction, leading to significant variation of substrate growth temperatures [START_REF] Vexler | Degradation effects in the one-band-tunneling Au/CaF2/n-Si(111) MIS structures[END_REF][START_REF] Pasquali | Calcium fluoride on Si(001): Adsorption mechanisms and epitaxial growth modes[END_REF] .

Molecule adsorption and characterization

Following the experimental characterization of the bare CaF2 ultrathin insulating layer, the sample is extracted from the STM and kept at low temperature (12 K) to be exposed to a flux of iron tetraphenylporphyrin (FeTPP) molecules via the heating of a PBN Knudsen cell at ~ 230°C. The fixed exposure time (2 s) leads to a coverage of ∼ 0.4 monolayer. Note that in the following, we will consider that the chlorine apical ligand initially fixed on the Fe atom of the FeTPP molecule is removed due to the evaporation process.

Theoretical methods and means.

We have used the Spanish Initiative for Electronic Simulations with Thousands of Atoms (SIESTA) [START_REF] Hohenberg | Inhomogeneous Electron Gas[END_REF][START_REF] Kohn | Self-Consistent Equations Including Exchange and Correlation Effects[END_REF] package and combined simulated annealing optimization technique to find the ground state structure of the CaF2 stripes obtained on the Si(100) surface. The Perdew-Burke-Ernzerhof (PBE) Generalized Gradient Approximation (GGA) for the exchange-correlation density functional was employed to determine the total energies [START_REF] Perdew | Generalized Gradient Approximation Made Simple[END_REF][START_REF] Ordejon | Self-consistent order-N density-functional calculations for very large systems[END_REF] . During the annealing simulations, the atoms motions follow the Verlet algorithm velocities with a time step of 1 fs [START_REF] Toton | Temperature control in molecular dynamic simulations of non-equilibrium processes[END_REF] . The system is then raised at a high temperature (1000 K) and slowly cooled down to 4 K in about 20000 steps. The relaxation of the entire system (CaF2 molecules + WL) is performed with a grid of 9 x 9 x 3 k-points giving a total of 135 k-points in the irreducible Brillouin Zone. Then, the following standard set of parameters are chosen such that the self-consistency mixing rate is fixed to 0.1, the maximum force tolerance is set to 0.02 eV.Å -1 and the mesh cut-off is adjusted at 400 Ry. The calculations are performed without spin polarization and a basis set of localized atomic orbitals (double- plus polarization functions) with norm-conserving pseudopotentials are employed. The self-consistent cycles were stopped when the variations of the total energy per unit-cell and the band structure energy are both lower than 10 -4 eV. The final optimized unit-cell (i.e., 23.20 x 7.78 x 44.50 Å 3 ) contains 156 atoms (i.e. 4 Ca, 120 Si, 24 H and 8 F) and 10 Si layers in order to take into account subsurface interactions. For the calculations performed on the sole FeTPP molecule in the gas phase, we use the Gaussian V09 simulation package. The structure of the molecule is relaxed and the Kohn-Sham energies are computed with the HSE hybrid functional (HSEh1PBE). The C and H atoms are described with the 6-31G* basis set while the 6-311G* basis set is chosen for the Fe and H atoms.

RESULTS AND DISCUSSION

The epitaxy of the Si(100) surface by CaF2 molecules follows a Volmer-Weber (VW) growth law.

The initial stage of the epitaxy in which the formation of a WL occurs, previously studied by our team, was investigated at a low CaF2 coverage (~ 0.3 monolayer) [START_REF] Chiaravalloti | Atomic-scale study of the adsorption of calcium fluoride on Si(100) at low-coverage regime[END_REF] . The WL formation implies that the silicon surface is periodically etched during the adsorption/dissociation of the CaF2 molecules to form a (2x3)

unit-cell as recalled in Fig. 1a. The WL forms patches appearing as dark corrugations in Fig. 1b. Inside these patches, each unit-cell is oriented along the silicon dimer rows [110] direction and their relative direction can be identical or head-to-tail [START_REF] Chiaravalloti | Atomic-scale study of the adsorption of calcium fluoride on Si(100) at low-coverage regime[END_REF] . Increasing the amount of CaF2 molecules during surface exposition results in observing the second step of the VW process leading to the formation of ultra-thin ribbons of stripes, as it can be observed in Fig. 1b. At this stage, it is unknown if the additional CaF2 molecules are partially dissociated or if they are kept unspoiled to form the stripes. Additionally, the electronic insulating character of these stripes in not yet demonstrated [START_REF] Chiaravalotti | Atomic scale control of hexaphenyl molecules manipulation along functionalized ultra-thin insulating layer on the Si(100) surface at low temperature (9 K)[END_REF] and the precise atomic scale structure of the ribbons of stripes remains unknown.

A careful look in Fig. 1b shows that a ribbon is composed of several parallel stripes oriented perpendicularly to the unit-cells of the WL, i.e. the silicon dimer rows. Note that the stripes are surrounded by either residual bare silicon dimer rows or spots of WL [START_REF] Chiaravalloti | Atomic-scale study of the adsorption of calcium fluoride on Si(100) at low-coverage regime[END_REF] . The averaged distance between each stripe is 11.7 ± 0.3 Å. Paying attention on each stripe, one can identify that they appear to be composed of a series of twisted chevrons. As we emphasized, the ribbon of stripes seems to be sitting on the WL. One of the important parameter for the understanding of the growth of a CaF2 semi-insulating layer is thus its relative orientation between the WL unit-cells.

To investigate the inner structure of a stripe, we have enhanced the measured height variations of a portion of a ribbon via a three dimensional representation of the STM topography. It reveals a measured corrugation between two stripes of ~ 0.5 Å (Fig. 2a, see also the supplementary Fig. S1). The stripes appear to be composed of left and right chevrons, each of them made of shifted bright features.

The red dotted lines in Fig. 2a locate the chevrons maxima. The zoom on a single stripe shown in Fig. 2b estimates precisely the separation between the left and right chevrons in the order of ~ 1.4 Å.

The atomic scale structure of a ribbon of stripes can also be compared with the relative positions of the silicon atoms surrounding the stripes as shown in Fig. 2c. By locating the direction of the silicon dimer rows (horizontal red dotted lines) and the maximum density of state (DOS) intensity at the stripes (horizontal blue dotted line), one can determine that both have the same periodicity (7.8 ± 0.2 Å and 7.9 ± 0.3 Å, respectively). One can also notice that the lateral distance between these two directions is similar to the size of a silicon dimer row width (i.e. 2.6 ± 0.2 Å). The STM image shown in Fig. 2c allows to locate the position of each silicon dimers along the bare Si(100) surface, via the identification of the silicon back-bonds (BB) directions [START_REF] Yengui | Atomic scale study of corrugating and anticorrugating states on the bare Si(100) surface[END_REF] by vertical dotted white lines (Fig. 2c). A detailed explanation of the positioning of the back-bonds is recalled in Fig. S2 and are observed as darker spots of DOS separated by brighter lines in the back-bond rows. Combining these two perpendicular directions (red horizontal and white vertical dotted lines) forms a grid that can be extended and superimposed over the ribbon of stripes area. From this, we can locate the relative positions of the oriented WL unit-cells in the area of the ribbon of stripes, as if they were part of this structure. The direction of the WL unitcell is here chosen via a careful comparison of the surrounding of the ribbon of stripes [START_REF] Chiaravalloti | Atomic-scale study of the adsorption of calcium fluoride on Si(100) at low-coverage regime[END_REF] . This assumption reveals how the substitutional Ca atoms of the WL can be aligned along the stripes (light green balls of the cells). Coherently to the second Volmer-Weber growth phase, when additional CaF2 molecules are evaporated over these areas, they are not likely to dissociate during their adsorption, as for the formation of the WL, but rather interact with the existing structure as an interstitial element.

Hence, to form the observed ribbon of stripes oriented in the [1-10] direction, it is consistent to consider that the additional CaF2 molecules are mostly located in between each WL unit-cell and most probably within the substitutional Ca atoms of each cells.

To understand how the additional CaF2 molecules react with the organized WL, we have performed DFT calculations on a silicon slab having a surface area made of 4 WL unit-cells (see section 2.1 for details). We have thus based our investigation by adding additional CaF2 molecules near two consecutive Ca restatoms of two WL unit-cells. In a first step, the entire relaxed geometry of the slab is obtained from DFT calculation by optimizing the energy of the initial large structure of the wetting layer for both Si atoms and surface unit-cell. In a second step, the requested number of CaF2 molecules (four) is added on the designed slab and we then proceed to the annealing and relaxation of the whole system (see Fig. S3 for further details). To simulate the experimental annealing and reproduce the dynamics of the ribbon formation, the random initial velocities, corresponding to a temperature of 1000 K, are assigned to all the atoms of the surface by using Maxwell-Boltzmann distribution.

The final relaxed structure is shown in Fig. 3a-c. Figs. 3b and3c show the two side views of the slab as described in the top view in Fig. 3a. It is interesting to notice that, following the relaxation, the substitutional Ca atoms are not anymore centered at the missing Si dimer of the WL unit-cell but shifted towards the two F atoms (F1) that passivate the neighbor Si dimer. Our calculations show that the stripes shape observed in Fig. 2 are formed via the intercalation of additional CaF2 molecules (Ca1 and F2 in Fig. 3a) along with the Ca of the WL unit-cell. Here, the interactions of the Ca atoms with the four F atoms (i.e. two chemisorbed on the Si dimer of the WL cell and the two from the CaF2 molecule) are significant for the stabilization of the entire stripe structure. As a consequence, the distance that separates two consecutive Ca atoms along a stripe is ~1.4 Å while the side views in Figs. 3b, 3c reveal a height variation between two successive Ca atoms of ~ 0.7 Å. Hence, the calculated periodicity between two repeated stripes is 11.7 Å (Fig. 3c). Logically, the length separating two chevrons (i.e., two substitutional Ca atoms) is ∼7.6 Å. For the sake of clarity, we have also compared the calculated local density of states (LDOS) distribution of the simulated surface with the experimental STM images (Figs. 3d andS4). All these data are in very good agreement with the experimental measurements reported in Figs. 1 and2.

It is now essential to examine the electronic structure of the ribbon of stripes. For this, we have measured the averaged differential conductivity by acquiring various dI/dV curves at different positions across a ribbon of stripes. The result of the averaged measurements is presented in Fig. 4a. The surface gap energy can be deduced by defining the asymptotic intersections at the valence and conduction bands edges with the zero conductance plateau. The crossing values worth -1.13 ± 0.10 V and 2.09 ± 0.10 V, giving a total surface gap energy of 3.22 ± 0.20 V. This experimental value can be compared with a theoretically estimate of the surface gap energy of the semi-insulating layer performed via a specific calculation. We used the DFT+U approach method implemented in SIESTA based on the Dudarev et al. scheme [START_REF] Dudarev | Electron-energyloss spectra and the structural stability of nickel oxide: An lsda+u study[END_REF] that combines the two parameters U and J to produce an effective Coulomb repulsion energy defined by U eff = U -J. In order to retrieve the experimental surface gap energy, given the intrinsic difficulty in determining the ab-initio value of Ueff., we have computed the surface gap evolution as a function of Ueff varying from 2 eV to 30 eV. Although the implemented DFT+U approach in SIESTA allows defining independently the U and J parameters for each atomic shell, we have chosen to use the same Ueff value for the Ca, Si and F atoms. Each PDOS curve is defined by 500 points spanning over the [-20 eV to 10 eV] energy window from either side of the Fermi energy value. The smearing energy used for the PDOS curves is fixed at 0.3 eV. The ensuing evolution of the calculated surface gap as a function of the tested Ueff. values is reported in Fig. 4b. The surface gap remains negligible (ie < 200 meV) for Ueff. varying between 0 eV and 4.45 eV and then increases almost linearly until Ueff.

reaches 26.45 eV to finally decreases sharply. Therefore, we deduced that the most accurate value of Ueff. reproducing the measured surface gap energy on the ribbon of stripes is 26.45 eV. An example of a PDOS curve at this Ueff. value is given in Fig. 4c with the detailed contribution of the F, Si and Ca atoms. Note that there are no dopants atoms in the considered slab for the calculations. This can explain why the experimental and theoretical Fermi energy are not the same in Figs. 4a and4c. It is relevant to observe that the Hubbard correction in the DFT+U method induces energy shifts of the occupied states towards lower energies, rendering the estimation of the surface gap energy relatively accurate. From the subsequent total PDOS of the considered example reported in Fig. 4c, it is possible to estimate a calculated surface gap energy of 3.1 eV (Fig. 4d).

The charge states of the various elements forming the stripes are analyzed via the Bader scheme [START_REF] Bader | A Quantum Theory of Molecular Structure and its Applications[END_REF][START_REF] Henkelman | A fast and robust algorithm for bader decomposition of charge density[END_REF] .

The initial effective charge for the valence electrons of the Ca atoms is 2e. After relaxation (without Hubbard correction), the charges of the residual Ca of the additional CaF2 molecules (Ca1 in Fig. 3a) are at 0.891e and 0.897e, respectively, thus having lost 1.109e and 1.103e. When the Hubbard correction is applied for fitting the experimental surface gap energy, the Ca effective charge is worth 0.173e and 0.171e, leading to an even stronger charge loss (i.e. 1.827e and 1.829e, respectively). Concerning the substitutional Ca atoms of the WL (Ca(2) in Fig. 3a), their charge states are slightly different (0.768e without Hubbard correction and 0.202e with correction) but show the same trends ( +1.80e). The charge variation of the F atoms changes in the opposite way, as one would expect, mimicking the CaF2 ionic crystal. Here, the F atoms have an initial charge of 7 electrons. With Hubbard correction, the F atoms attached on the Si dimers nearby the substitutional Ca2 atoms (F1 in Fig. 3a) win negative charges to reach 7.59e whereas the charge of the F atoms forming the CaF2 molecule is slightly higher with 7.82e.

This reveals that the F atoms of the CaF2 molecules added on the slab remain strongly bonded to the Ca atom and form an ionic bonding network with the substitutional Ca atom of the WL layer. Note that our calculated effective charge of a CaF2 molecule are similar to former work, i.e. a loss of ~1.80e for Ca + and a gain of ~ 0.88e for F -, respectively [START_REF] Shi | First-principles calculations of the CaF 2 bulk and surface electronic structure[END_REF] . Therefore, we can conclude that the simulated stripes structure that takes into account the Hubbard correction fits correctly our experimental observations and shows a good trend of the electronic structure of the insulating layer. A detailed description that summarizes these data is given in the supplementary Fig. S5. It is important to underline that the relatively high energy of Ueff. needed to reproduce the experimental surface gap energy of ~ 3.2 eV is not so surprising considering the large amount of computational parameters that may affect this tuning value, and the lack of initial localization in the exchange correlation functional that traduce Coulomb interactions. One can however observe that the Hubbard correction affect the charge state of the Ca and F atoms of the insulating layer in a way where the ionic properties of the Ca-F ionic bonding is enhanced.

However, as shown in Fig. S6, the geometry of both type of Ca atoms (Ca1 and Ca2) of the insulating layer is only weakly affected (less than 2 %) by the Hubbard correction Ueff. = 26.45 eV. Note that other approaches using ab-inito method such as unrestricted Hartree Fock may also give interesting results but are beyond the scope of the present paper [START_REF] Yu | Comparing ab initio methods of obtaining effective U parameters for closedshell materials[END_REF] .

To test the electronic semi-insulating properties of the ribbon of stripes, we have studied how a FeTPP molecule is perturbed when adsorbed on the epitaxial surface. As previously investigated, this molecule shows, on this surface, two main conformations having a mirror symmetry [START_REF] Ramos | Probing charge transfer dynamics in a single iron tetraphenylporphyrin dyad adsorbed on an insulating surface[END_REF] . Only one of these configurations is considered here (Figs. 5a,5b). While the molecule may be initially considered as physisorbed, its electronic structure on the semi-insulating surface is clearly unknown.

The ensuing conformation of a FeTPP molecule adsorbed on a stripe is detailed in Fig. 5b. Further details of the considered slab for this calculation are provided in Fig. S8. In order to take into account Van der Waals interaction between the substrate and the molecule, relaxation of the overall system was performed with double-plus polarization functions orbitals with VdW-DF functional (DRSLL) [START_REF] Dion | Van der Waals Density Functional for General Geometries[END_REF][START_REF] Román-Pérez | Efficient Implementation of a van der Waals Density Functional: Application to Double-Wall Carbon Nanotubes[END_REF] .

From these calculations, the relative height of the FeTPP molecule compared to the surface can be deduced. For example, the Fe atom of the FeTPP (center of the molecule) is located at 5.4 Å from the surface. The nearest atoms of the molecule from the surface are hydrogen atoms of the phenyl rings located along the stripe with a typical distance of 2.9 Å. These values confirm the physisorbed character of the adsorbate. The calculated STM image of a FeTPP molecule adsorbed in this conformation is shown in Fig. 5d and presents good agreements with the experimental one (Figs. 5a, see also the Fig. S7 for additional details). To highlight the perturbations of the surface on the molecule or vice versa, the Bader charges are computed on the whole slab. Here, the calculated total charge transfer between the substrate and the molecule is relatively low and worth 0. one can see two mains PDOS peaks at -2.4 eV and 2.8 eV with two weaker satellites peaks at -1.1 eV and 0.9 eV. Surprisingly, the PDOS curves calculated at the four pyrroles of the FeTPP molecule (Fig. 6c) exhibit DOS peaks at -1.1 eV and 0.9 eV, i.e. at the same energy of the satellite PDOS peaks observed in Fig. 6b. The dI/dV peaks observed at the pyrroles locations on the FeTPP at ± 1.6 V can be related with the calculated PDOS satellite peaks in Figs. 6b and6c. Their relative weak dI/dV intensities also reveal that the insulating layer may hinder the accurate measurement of the frontier orbitals HOMO-LUMO gap of the molecule.

Generally, when adsorbates are interacting with surfaces the HOMO-LUMO gap energy of the molecules known in gas phase can be significantly reduced 44 , especially if chemisorption occurs. On insulating layers, another effect can take place, arising from the potential loss at each interfaces of the double STM junction 45 , involving higher applied voltages to reach frontier orbitals. Looking at the symmetrical position of the dI/dV peaks in Fig. 6a and PDOS in Fig. 6b

ASSOCIATED CONTENT

Supporting information

The supporting information is available and attached to the submission of this manuscript as the file CaF2_analysis_SUPPL_material.pdf

FIGURES CAPTIONS:

BIBLIOGRAPHY:

1 Ren, F.; Wide, J.C.Z. Energy bandgap electronic devices, Word Scientific Publishing, USA, ISBN 981-238-246-1

  053e. In order to further highlight the interaction between the molecule and the substrate, we have computed the variations of the LDOS in the slab. It is obtained when the LDOS is computed for the substrate (LDOSsub.) and the molecule (LDOSMol.) separately, in one first step. The difference LDOS) is then achieved, as a second step, via the subtraction of the total LDOSTot. computed when the molecule is adsorbed on the surface with the two other values (LDOS) = LDOSTot. -LDOSsub. -LDOSMol.). The results of the charge densities differences are shown in Figs5e and 5f. The red and blue iso-surfaces represent positive or negative differences of the LDOS) values, respectively. One can firstly observe that the LDOS) is globally weak since the selected isodensity values is in the range of 10 -4 e/Å -3 . Furthermore, the LDOS variations are mainly concentrated on the phenyls of the FeTPP molecule and especially on the two phenyls located along the insulating stripe (see black arrow in Fig.5efor Ph1 and Ph2). The concentration of LDOS) on the upper and lower phenyls is further detailed in Fig.5f, which mainly reveals that the lower part of the molecule is perturbed by the surface. A detailed analysis of the molecule-surface interactions reveals that after the FeTPP molecule adsorption, one of the lower carbon atoms from Ph2 can lose up to 0.09e, while the carbons atoms of Ph1 are less impacted (maximum gain of 0.008e). The charge state of the hydrogen atoms from the two considered phenyls are not impacted at all for Ph1 and only slightly changed for Ph2 (gain of 0.02e). As a consequence, the underlying Ca atoms below Ph2 and Ph1 lose both ~ 0.05e. The F atoms in the vicinity of these phenyl rings are also gently impacted with a maximum charge gain of 0.03e. Considering the relatively long distance separating the lowest hydrogen atom of the FeTPP molecule to the surface, these small charge perturbations are coherent with van der Waals forces interactions. A detail analysis of the charge state distributions of the FeTPP molecule in interaction with the surface is provided in Fig.S9. It is important to underline that the charge variations presented in the case of the bare insulating surface (Figs.3 and S4) are slightly different due to the fact that the Hubbard correction is not taken into account in the case of the calculations of the molecule on the surface.Similarly to what has been done with NaCl insulating layers in the presence of charged adsorbates[START_REF] Repp | Controlling the charge state of individual gold adatoms[END_REF] , it is interesting to describe how the surface structure may be modified because of the presence of the FeTPP molecule. The investigation of the atomic displacement of the first two layers of the semiinsulating layer (Ca and F) indicates that only the atoms of the stripe on which the FeTPP molecule is straddled are faintly impacted by the adsorbate, whereas the surrounding of the molecule is not. For all the considered atoms, the displacements are less than ± 0.15 Å in both the [110] and [1-10] directions.For the vertical direction, i.e. perpendicular to the surface, it mainly occurs at the two substitutional Ca atoms having vertical displacements of ~ 0.25 Å. Additional information concerning these displacement is provided in Figs. S10.It is now crucial to determine if the considered semi-insulating ribbon of stripes are able to correctly electronically decouple the FeTPP adsorbate with a good efficiency. The dI/dV curves acquired at three different parts of the molecule shown in Fig.6aexhibit flat signals in the range -1.2 V to 1.5 V. Small peaks of density of states measured at -1.6 V and +1.6 V, at the pyrroles locations (red dot in the inset of Fig.6a) indicate a probable HOMO-LUMO gap of 3.2 eV. The two dI/dV curves acquired at the phenyls and central part of the molecule are rather similar and show an occupied DOS peak at -2.4 V below the surface Fermi level whereas the unoccupied states can progressively span up to 2.5 V. These experimental data can be compared to the calculated PDOS at specific areas of the molecule as illustrated in Figs.6b and 6c. When the PDOS includes only the phenyl groups of the FeTPP molecule (Fig.6b),

  compared to the Fermi level energy, our results indicate that the electrochemical potential of the adsorbed FeTPP molecule is weakly perturbed by the insulating layer. It also shows that the total voltage drops at each STM junction (i.e. silicon-molecule and molecule-tip) in the range of 0.4 eV. The FeTPP molecule orbitals energies calculated in gas phase are reported in Fig. 6d and clearly indicate that a group of orbitals (N° 169 to 176) having almost degenerated energies levels are the HOMO -LUMO frontiers orbitals as measured in the dI/dV and PDOS curves in Figs. 6a and 6b. These orbitals mainly involve the central macrocycle and especially the pyrroles groups of the porphyrin. Coherently, the phenyl rings of the FeTPP molecule are involved at orbitals of higher or lower energies.4. CONCLUSIONIn summary, we have performed the first complete experimental and theoretical investigation of the structural and electronic description of CaF2 ribbons of stripes at the nanoscale. Our work shows that the initial formation of a wetting layer on the Si(100) surface is the first stage of the growth of ribbons of CaF2 stripes. A detailed analysis of the STM images acquired at low temperature (9K) provides a clear description of the relative positioning of the additional CaF2 molecules within the existing wetting layer structure. The characterization of the observed epitaxial structure is supported by precise DFT calculations of the ensuing surface geometry and compared with the acquired STM images. By using the DFT+U method, the electronic structure of the surface gap energy of a ribbon of stripe reproduces the one measured experimentally. In particular, we have shown that the effective charges on the Ca and F atoms of the insulating layer are similar to those determined on bulk CaF2 surface reconstruction. Thus, our findings imply that the electronic insulating properties are efficient from one single monolayer. To further test the electronic properties of the CaF2 insulating layer, we have studied the interactions of a single FeTPP molecule with the surface structure as it appears on the STM images.Weak interactions between the surface and the adsorbate are observed via the study of the LDOS difference between the molecule and the surface. A detailed analysis of the charge state of the adsorbed FeTPP molecule indicates typical van der Waals interactions. The electronic properties of the FeTPP molecule is described via dI/dV tunnel spectroscopy measurements acquired at several strategic locations. The comparison of these data with ad-hoc calculations of the FeTPP molecule on the surface and in gas phase further confirms that the electronic structure of the adsorbate is almost not affected by the CaF2 insulating layer. The ensemble of these findings endorses that the electronic charge transfer between the adsorbate and the semi-insulating layer is weak 46 . It also demonstrates the clear insulating properties of the described CaF2 ribbon of stripes. Such insulating layer on the Si(100) surface will definitively open new perspectives in the control of electronic, optic and magnetic devices at the nanoscale.

Figure 1 :

 1 Figure 1: (a) Recall of the three dimensional balls and sticks structure of the wetting layer (WL) unit-

Figure 2 :

 2 Figure 2: (a) Three dimensional representation (perspective) of the stripes structure of a small section

Figure 3 :

 3 Figure 3: (a) Top view of the considered silicon slab of the insulating layer electronic properties

Figure 4 :

 4 Figure 4: (a) Semi-logarithmic representation of dI/dV spectroscopic curve resulting of the average of

Figure 5 :

 5 Figure 5: (a) 7.7 x 3.9 nm² STM topography (I = 12 pA, V = -2.7 V) of a FeTTP molecule adsorbed on

Figure 6 :

 6 Figure 6: (a) Averaged measured dI/dV curves acquired at 3 different locations on top of the FeTPP

Moon, H.; Seong, H.; Shin, W. C.; Park, W.T.; Kim, M.; Lee, S.; Bong, J.H.; Noh, Y.Y.; Cho, B.J.; Yoo, S.; Im, S.G. Synthesis of ultrathin polymer insulating layers by initiated chemical vapor deposition for low-power soft electronics. Nature Mat. 2015, 14, 628-635.

Fernández Torrente, I.; Franke, K. J.; Pascual, J. I. Spectroscopy of C60 Single Molecules: the Role of Screening on Energy Level Alignment. J. Phys.: Condens. Matter 2008, 20, 184001-184012.

Nazin, G.V.; Wu, S.W.; Ho, W. Tunneling rates in electron transport through double-barrier molecular junctions in a scanning tunneling microscope. PNAS, 2005, 102, 8832-8837.

Labidi, H.; Sonnet, Ph.; Riedel D. Electronic control of the tip-induced hopping of an hexaphenylbenzene molecule on a bare Si(100) surface at 9K. J of Phys. Chem. C 2013, 117, 13663-13675.

AUTHOR INFORMATION

Corresponding author:

Email: damien.riedel@u-psud.fr, ORCID: 0000-0002-7656-5409