Fan Xie

Yuxiang Zhang
email: yuxiang.zhang@outlook.com

Eric Larose

Aroune Duclos

Su Chen

Xiaoyun Li

Chunlong Fei

Characterizing mechanical change in metals using amplitudemodulated diffuse ultrasound

Keywords: diffuse ultrasound, nonlinear effect, coda wave interferometry, amplitude-modulation, aluminum alloy, mechanical change

In this paper, we present an ultrasonic method based on diffuse ultrasound with successive excitation amplitudes. The system provides amplitude-dependent parameters of diffuse ultrasound using coda wave interferometry, and can be used to characterize mechanical change in metallic materials. Localized mechanical change caused by instantaneous 400 o C thermal shocking in a meter-scale aluminum alloy slab were successfully characterized using variations in velocity and decorrelation coefficients with excitation amplitudes. We discuss the mechanisms and spatial distribution potentially causing the observed amplitudedependent diffuse waveform modification. Combining the method presented here with complementary approaches will enhance the ability to nondestructively detect early-stage damage in metals either in the laboratory or for on-site applications.

Introduction

Due to their direct sensitivity to the elastic properties of materials along with their costeffective and reliable performance, ultrasound-based Non-Destructive Testing (NDT) techniques provide a primary tool to assess the condition, integrity and reliability of a wide range of metals, and to monitor for potential risks throughout their life cycle. In recent years, research has sought techniques to detect the initiation of damage as early as possible, playing a key role in the development of NDT approaches. Indeed, mechanical changes which cause damage in its very early stages may jeopardize the normal operation of a material. It is therefore necessary to develop more accurate and sensitive ultrasound-based techniques to assess material structures.

Among the emerging techniques, nonlinear diffuse ultrasound shows great promise since the scattered waves are more sensitive to the nonlinear elastic response of the material than direct waves. Consequently, it provides information that is complementary to that provided by common bulk nonlinear techniques when performing global/local inspection of a material's integrity at the early stages of damage. For instance, depending on the quasi-static acoustoelastic effect [START_REF] Zeiger | Measurement of acoustoelastic coefficients of rayleigh waves in steel alloys[END_REF] , high-order nonlinear elastic constants can be determined by monitoring velocity changes in diffuse waves at different times thanks to coda wave interferometry (CWI) performed during very small incremental stress solicitations (down to a few kPa) [START_REF] Larose | Monitoring stress related velocity variation in concrete with a 2× 10-5 relative resolution using diffuse ultrasound[END_REF]3 . A particularly attractive nonlinear elastic effect, time-logarithmic recovery (referred to as slow dynamics) back to the unperturbed elastic modulus following a sharp drop in the elastic modulus (referred to as fast dynamics) has been reported in response to moderate mechanical solicitations [START_REF] Johnson | Slow dynamics and anomalous nonlinear fast dynamics in diverse solids[END_REF][START_REF] Tremblay | Probing slow dynamics of consolidated granular multicomposite materials by diffuse acoustic wave spectroscopy[END_REF] . Such nonlinear responses were first probed with nonlinear resonant ultrasound spectroscopy (NRUS) [START_REF] Ulrich | Determination of elastic moduli of rock samples using resonant ultrasound spectroscopy[END_REF] , and it can also be monitored efficiently with velocity changes from CWI.

More recently, several authors [START_REF] Riviere | Pump and probe waves in dynamic acousto-elasticity: Comprehensive description and comparison with nonlinear elastic theories[END_REF][START_REF] Hilloulin | Small crack detection in cementitious materials using nonlinear coda wave modulation[END_REF][START_REF] Zhang | Nonlinear coda wave interferometry for the global evaluation of damage levels in complex solids[END_REF] proposed an alternative nonlinear "pump-probe" method consisting in measuring low-amplitude diffuse waves at high frequencies (known as the HF probe wave) by CWI to detect the elastic changes induced by another large-amplitude wave excitation at a lower frequency (LF pump wave). In these experiments, both excitations were performed simultaneously, with the probe wave (CWI) triggered several times during the pump excitation. This pump excitation is thought to activate nonlinear behavior in cracks present in an initially linear elastic medium, thus altering the material's elasticity. This technique can therefore assess overall damage levels by quantifying CWI versus the pump level, which derived from the so-called "quadratic hysteretic nonlinearity". The nonlinear response depends on the presence of micro cracks or soft inhomogeneities that act as nonlinear sources [START_REF] Guyer | Nonlinear mesoscopic elasticity: Evidence for a new class of materials[END_REF][START_REF] Solodov | Can: an example of nonclassical acoustic nonlinearity in solids[END_REF] . Recent developments [START_REF] Zhang | Nonlinear coda wave interferometry for the global evaluation of damage levels in complex solids[END_REF][START_REF] Solodov | Can: an example of nonclassical acoustic nonlinearity in solids[END_REF][START_REF] Zhang | Nonlinear mixing of ultrasonic coda waves with lower frequency-swept pump waves for a global detection of defects in multiple scattering media[END_REF] show that the relative wave velocity change being linearly proportional to the pump wave amplitude, meanwhile the pump wave amplitude also leads to a quadratic increase in decorrelation (kd).

Nevertheless, this type of monitoring remains challenging from the NDT point of view because the resolution is much larger than that of the micro cracks: at least several tens of wavelengths in a heterogeneous medium [START_REF] Zhang | Nonlinear coda wave interferometry for the global evaluation of damage levels in complex solids[END_REF][START_REF] Lake | Dynamic acousto-elastic testing of concrete with a coda-wave probe: Comparison with standard linear and nonlinear ultrasonic techniques[END_REF] . Locating the change thus becomes extremely challenging. In addition, nonlinear diffuse wave techniques are less sensitive in homogeneous metals where changes induced by micro cracks only become detectable at a scale of a dozen of microns. In contrast, diffuse ultrasound is sensitive to changes in environmental (e.g. temperature, humidity etc.) [START_REF]A review of ultrasonic coda wave interferometry in concrete[END_REF][START_REF] Xie | Monitoring of environmental loading effect on the steel with different plastic deformation by diffuse ultrasound[END_REF] and operational conditions (e.g. the a priori reference state, external mechanical loading or excitation facilities), that are difficult to measure in normal NDT operation. Consequently, most current diffuse wave-based nonlinear ultrasound techniques only work in laboratory conditions, where damage detection resolution and the dimensions of the test specimen are both limited [START_REF] Hilloulin | Small crack detection in cementitious materials using nonlinear coda wave modulation[END_REF][START_REF] Zhang | Nonlinear mixing of ultrasonic coda waves with lower frequency-swept pump waves for a global detection of defects in multiple scattering media[END_REF][START_REF] Legland | Evaluation of crack status in a meter-size concrete structure using the ultrasonic nonlinear coda wave interferometry[END_REF] .

Aluminum alloys are widely used in load-bearing applications (e.g. bridge decks, marine crafts, nuclear power engineering etc.). Aluminum is more subject to the alteration of mechanical properties following a fire as the phase transition temperatures for this material are significantly lower than that of steel [START_REF] Maljaars | Constitutive model for aluminum alloys exposed to fire conditions[END_REF][START_REF] Summers | Post-fire mechanical properties and hardness of 5083 and 6082 aluminum alloys[END_REF] . However, little research on damage has been done to assess the ability to relate changes in mechanical properties to microstructural alterations following an exposure to an elevated temperate [START_REF] Summers | Overview of aluminum alloy mechanical properties during and after fires[END_REF] .

In this article, we present a simple and robust high-frequency (HF) diffuse ultrasound-based method with successive excitation amplitudes, which expands to the early damage detection capabilities of the method. Nonlinear diffuse ultrasound is used to provide amplitudedependent parameters using CWI. Our goal is to quickly assess changes in mechanical properties at an early-stage damage in metals.

Materials and methods

Aluminum alloy sample

The tests were conducted on an intact 20 mm thick aluminum alloy slab (6061) measuring 1000 mm ×1000 mm. The chemical components of the aluminum slab are listed in Table 1. This alloy was selected for its prevalence among lightweight structural alloys. The basic properties of the aluminum alloy are as follows: P-wave speed Cp = 6.82 km/s, S-wave speed Cs = 3.46 km/s and mass density ρ=2.88×10 3 kg/m3.

Ultrasonic transducers

Broad band piezoelectric transducers (FUJI Ceramics 1045S) of diameter 20 mm were used because of their flat sensitivity over a wide frequency band (200 kHz ∼ 1.5 MHz). The transducers allow a broad range of acoustic amplitude measurements, thus ensuring that the real mechanical output amplitude will be proportional to the electric amplitude excitation delivered by the power amplifier.

Transmission and Acquisition

An arbitrary waveform generator (National Instruments PXI 5105) delivered chirp signals, with frequency varying between 1 MHz and 1.3 MHz, to the power amplifier (Ciprian US-TXP-3C). The gain of the power amplifier was set at 400 with ultra-low distortion and a high-speed slew rate from 10 kHz to 10 MHz. It allows 500-μs chirps to be output at incrementally increasing voltage amplitudes from 200 Vpp to 400 Vpp. The 4-ms received signals were synchronized to the transmission chirps and were recorded by an 8-channel 12-bits data acquisition system (National Instruments PXI 5421) at a sampling frequency of 10 MHz.

At the working frequencies, the wavelengths ranged from 3 to 7 mm, which is much smaller than the thickness of the plate. Waves could thus be multiply reverberated in the vertical direction. Waves also reverberated in the horizontal plane, but due to the dimensions of the sample, reverberations in the horizontal plane were negligible compared to vertical reverberations. Multiple reverberations yield coda-like waveforms that look like diffuse waveforms. Hereafter, the waveforms are noted as "diffusive" even though, strictly speaking, they should be referred to as mostly multiply reverberated.

Methodology and measurements

CWI analysis via amplitude-modulated diffuse ultrasound

CWI [START_REF] Douma | Coda wave interferometry for estimating nonlinear behavior in seismic velocity[END_REF] was applied to quantitatively reveal the amplitude-dependent relative velocity changes dv/v and decorrelation kd of coda waves that can be linked to the material's nonlinearity.

Due to its robustness with respect to noise, the stretching method 21 was adopted to determine dv/v and kd. In practice, the stretching method consists of two main steps: (1) a constant change in propagation velocity between the reference signal (h 1 (t)) and the current record (h i (t)) is assessed, and an attempt is made to compensate it by stretching h i (t) along its time axis to a certain ratio ε k ; (2) the stretched signal, i.e., h i [t(1 + ε k )] is then compared to the reference signal h 1 (t) to detect similarities in their waveforms, which can be assessed by computing their correlation coefficient CC(ε k ) within a given time window [t 1 t 2 ] : After a grid search of ε k over a range of plausible values, two parameters describing the change in propagation medium were obtained: the ε k that maximizes the CC(ε k ) was retained as the apparent velocity change dv/v = ε max ; and the microstructural modification of the medium was quantified based on the residual decorrelation coefficient kd = 1 -CC(ε max ).

It is worth to mention that the decorrelation (kd) allows one to observe the loss of coherence With the stretching method, CWI can simultaneously reveal the time-lapse velocity change and microstructural change in the propagation medium with a high sensitivity [START_REF] Larose | Monitoring stress related velocity variation in concrete with a 2× 10-5 relative resolution using diffuse ultrasound[END_REF][START_REF]A review of ultrasonic coda wave interferometry in concrete[END_REF] .

Without any LF pump wave, the amplitude-modulated diffuse ultrasound directly explores the so-called "quadratic hysteretic nonlinearity" by sending high-voltage amplitude diffuse waves, which are able to perturb the material elasticity. Therefore, at first order, we expect to measure the relative wave velocity change linearly proportional to the wave amplitude, meanwhile the wave amplitude increase lead to a quadratic increase in decorrelation. Below, the velocity change (dv/v) (resp. microstructural change (kd)) and the voltage amplitude transmitted (Amp) are proposed to satisfy the following empirical law to the first order (resp. second order):

where A dv/v and A kd are the two parameters used to characterize early-stage damage in this study. It is worth to note that the transmission voltage amplitude (Amp) should be selected high enough to achieve a significant level of nonlinearity. In our case, the transmission voltage levels ranged from 200 Vpp to 400 Vpp are selected, which are equivalent to an acoustic strain measuring ∼ 10 -7 to ∼ 10 -5 7 .

For validation purposes, as an example, the method was applied to three high-manganese steel specimens with early-stage damage due to fatigue as a result of plastic deformation. These dog-bone shaped specimens were cut from an intact steel plate made of highmanganese steel. The dimensions of the specimens were identical: 34 mm wide, 450 mm long and 10 mm thick. To produce different levels of fatigue damage, cycles of mechanical loading were carefully performed to produce plastic deformations at 6%, 8% and 10% on specimen #1, #2 and #3, respectively. A detailed description of the three specimens can be found in Xie et al. [START_REF] Xie | Monitoring of environmental loading effect on the steel with different plastic deformation by diffuse ultrasound[END_REF] . As illustrated in Fig. 1 These data demonstrate that both A dv/v and A kd provide a quantitative overall assessment of the specimens with different plastic deformations (despite the small deformation ≤ 10%), from early stages of steel fatigue. Moreover, A kd was shown to be more sensitive to the earlystage fatigue in steel than A dv/v , in line with the results observed in concrete [START_REF] Zhang | Nonlinear coda wave interferometry for the global evaluation of damage levels in complex solids[END_REF] .

Measurement procedure

As illustrated in Fig. 3 (a), nine ultrasonic transducers were distributed over a 1 m×1 m area and glued onto the top surface of an aluminum slab to probe different regions of the specimen.

Eight black transducers (labeled 1 to 8) served as receivers, whereas the single red transducer (labeled S) served as the emitter.

To produce local mechanical changes induced by exposure to a high temperate, a small region (marked by the red star) on the top surface of the slab was exposed to heat-shock at 400 o C for five minutes using a high-power hot gun (1500 Watt).

The measurements were conducted by imposing transmission chirps with amplitudes increasing in 20-Vpp steps from 200 Vpp to 400 Vpp. The first acquisitions were taken with the intact slab 5 min before applying the heat-shock. Subsequent measurements were performed in the state 5 min after the heat-shock. It is worth to note that these two measurements only took ~5 seconds which could significantly reduce the environmental inferences to the measurements.

To make sure the microstructural alterations due to heat exposure from heat-shock was correctly localized (and to avoid possible interference of the propagation of the elastic waves from mechanical contact thermometer), we used a hand-held inferred camera (Dali TX8, 384×288 spatial resolution and ±2 o C sensitivity) for contactless temperature monitoring.

GIVE THE MAX OBSERVED TEMPERATURE HERE. The finite element code COMSOL also verified the localized heat-shock processing in the slab (see the supplementary material).

According to the considerable amount of published papers focusing on the microstructural evolution of 6061 aluminum alloy during heat treatment, it can be observed that the grain size increases with the increase of temperature (>300 o C) and time. Therefore, we will attribute the localized change in mechanical properties of the aluminum alloy to the irreversible microstructural grain growth following exposure to heat shock.

At each voltage level, the signal-to-noise ratio (SNR) was improved by repeating the chirp transmissions 100 times and averaging the corresponding received signals.

At 1 MHz, aluminum has a shear wavelength of ∼3 mm which ensures the received signals are scattered mostly by the largest grains/aggregates as well as by boundaries and multiple scattering or multiple reverberations of waves can occur [START_REF] Weaver | On diffuse waves in solid media[END_REF][START_REF] Weaver | Temperature dependence of diffuse field phase[END_REF] . Stretching analysis was performed to extract two amplitude-dependent parameters: A dv/v and A kd by comparing the multiple scattered responses at each voltage level with the reference response at the lowest amplitude (200 Vpp).

Results and discussion

The experiment was performed in a regular office space and monitored using the procedures presented in Section 3.2. The received diffuse-like waveforms at voltage levels of 200 Vpp and 400 Vpp at transducer #8 (SR8 couple) were recorded in the initial intact state (Fig. 3 (b))

and in the damaged state (Fig. 3 (c CWI was then applied using the stretching method to quantify changes in apparent relative velocity and waveform dissimilarities, as a function of the source amplitude level. We compared eleven diffuse signals produced by incremental amplitudes to the signal obtained with the lowest source amplitude (200 Vpp). To enhance the stability of the cross-correlation coefficient measurements, we selected a broad time window between 1 and 3.5 ms.

Figures 4 and5 show the apparent relative velocity changes (dv/v) and decorrelations (kd) as a function of the source amplitude measured at eight transducers in the intact state (black dots) and the state after exposure to a 400 o C heat-shock (red dots).

We also compared the results (See Supplementary material) due to three different time windows including an earlier (0.5-2 ms), later (2-4 ms) and narrower (1.5-3 ms) one. Despite the change in time window, the results are in good agreement with the broad window we use (1-3.5 ms) which suggests that the result is (at first order at least) independent of the time window, and that a broader time window increases the measurement stability to characterize mechanical changes.

The relative velocity change was directly proportional to the excitation amplitudes, a result that has been observed in polymethyl methacrylate (PMMA) and aluminum alloy using dynamic acousto-elastic testing [START_REF] Call | Nonlinear elastodynamics in microinhomogeneous solids observed by head-wave based dynamic acoustoelastic testing[END_REF] . For the specimen at pre-heat-shock, the relative velocity change was 10 -5 per volt applied, which is half that of the specimen after heat-shock . These results are consistent with those obtained in previous studies [START_REF] Lake | Dynamic acousto-elastic testing of concrete with a coda-wave probe: Comparison with standard linear and nonlinear ultrasonic techniques[END_REF][START_REF] Riviere | Dynamic acousto-elasticity in a fatigue-cracked sample[END_REF] .

Figure 4. CWI can distinguish between intact and after heat shock aluminum based on apparent relative velocity changes (dv/v). Eight transducers placed on the aluminum alloy slab were used to acquire dv/v in its intact state (black dots) and damaged state following 400 oC thermal shocking (red dots). Measurements are plotted as a function of the source amplitude (Vpp).

dv/v dv/v o C Figure 5
. CWI can distinguish between intact and after heat shock aluminum based on decorrelations (kd). Eight transducers placed on the aluminum alloy slab were used to acquire kd for the intact slab (black dots) and following 400 o C thermal shocking (red dots). Data are plotted as a function of the source amplitude (Vpp).

To allow comparison, A dv/v and A kd acquired at each source-receiver couple before and after damage are plotted in Fig. 6. The intact specimen shows little variance of either A dv/v (dark black bars) or A kd (dark red bars) across all eight source-receiver pairs. In contrast, a significant increase in both A dv/v (light black bars) and A kd (light red bars) was observed for all source-receiver pairs after the heat-induced mechanical change. Moreover, the highest A dv/v and A kd values (∼2/3 times higher than the other source-receiver couples) were found for the SR8 couple, which is positioned directly symmetrical to the heat-induced change.

In the presence of local change, the A dv/v and A kd values were more variable than in the preheat-shock state. The significant variance can mainly be attributed to the uneven distribution of diffuse wave sensitivities, which depend on the locations of the transducers. Similar to the work of Pacheco and Snieder [START_REF] Pacheco | Time-lapse travel time change of multiply scattered acoustic waves[END_REF] and Larose et al [START_REF] Larose | Locatingasmallchangeinamultiplescattering environment[END_REF] , we can identify sensitivity kernels based on the propagation of the intensity within the plate. Contrary to the diffusion equation, which holds in multiple scattering media, for this system we must take into account multiple reverberation of the energy on the vertical axes, and on horizontal axes. This reverberation can be numerically calculated and will be the subject of further investigations. For the moment, we can only hypothesize, since the highest value for A kd was observed for the closest source-change-receiver combination, that an inverse problem based on proper sensitivity kernels can locate the change. The results obtained from amplitude-dependent diffuse-like waves raise another question: why are both A dv/v and A kd sensitive to the microstructural alteration exposed to heat-shock in the test specimens?

To address this question, we note that the increase in A dv/v and A kd with the source amplitude level is very similar to the amplitude dependency observed in strong heterogeneous media using low frequency (LF) pump waves [START_REF] Zhang | Nonlinear coda wave interferometry for the global evaluation of damage levels in complex solids[END_REF][START_REF] Lake | Dynamic acousto-elastic testing of concrete with a coda-wave probe: Comparison with standard linear and nonlinear ultrasonic techniques[END_REF] . For example, CWI at several hundred kHz has been used as probe wave with an amplitude-modulated frequency-swept pump wave at a few kHz to detect millimeter-scale cracks in homogeneous solids. For these types of medium, various possible explanations were proposed based on previous studies [START_REF] Riviere | Pump and probe waves in dynamic acousto-elasticity: Comprehensive description and comparison with nonlinear elastic theories[END_REF][START_REF] Tournat | Nonlinear effects for coda-type elastic waves in stressed granular media[END_REF] . These explanations are compatible with the widely accepted theory of mesoscopic nonlinearity, which states that the nonlinear response depends on the presence of micro defects or soft inhomogeneities that act as nonlinear sources altering the overall level of the material's nonlinearity. This type of nonlinear behavior reduces (softens) the resonance frequency. The softening of the resonance frequency can be directly compared to the CWI parameter dv/v, which is directly proportional to the LF pump wave amplitude. The quadratic increase in A kd is more complex to explain and will require further investigation.

Even at low excitation levels (10 -7 ), the hysteretic nonlinearity in metals has been widely documented [START_REF] Zeiger | Measurement of acoustoelastic coefficients of rayleigh waves in steel alloys[END_REF][START_REF] Johnson | Slow dynamics and anomalous nonlinear fast dynamics in diverse solids[END_REF][START_REF] Riviere | Dynamic acousto-elasticity in a fatigue-cracked sample[END_REF][START_REF] Nagy | Fatigue damage assessment by nonlinear ultrasonic materials characterization[END_REF] .

It is worth noting that changes in weak contacts of the microstructural alteration at the grain scale are thought to be responsible for the main contribution, especially for HF diffuse wave

A dv/v A kd
acoustic energy transmission (excitation voltage amplitude). The opening or closing of weak contacts due to the acoustic energies (10 -7 ∼ 10 -5 ) of the passing waves may cause dynamic switching of the reverberation paths. This phenomenon could explain the nonlinear behavior observed in the weakly heterogeneous metal specimens tested here. Although the acoustic strains induced by amplitude-modulated waves are 1-2 orders of magnitude smaller than those induced by LF pump waves, this hypothesis is in agreement with the behavior of the pump wave in heterogeneous media. Additional insights may be obtained by observing micro defects using diffuse waves at millimeter-scale wavelengths. Numerical study [START_REF] Xie | A bayesian approach for high resolution imaging of small changes in multiple scattering media[END_REF] has shown that the long propagation paths of diffuse waves in a medium can enhance localized spatial resolution of the changes at its wavelength ∼10-fold. As a result, here, we can detect the micro defects induced at a distance of several hundreds or dozen of microns.

In principle, modifications to the acoustic properties of the waveform following strong excitation by HF-amplitude-modulated diffuse-like waves should be particularly sensitive to weak contact changes at grain scales induced by heat-shock . This was confirmed by the greater sensitivity of A kd than A dv/v to both early fatigue damage in steels and heat-induced mechanical change in the aluminum alloy slab. However, the physics behind these nonlinear theories in metals is an ongoing research topic.

Conclusion

In this study, we used a novel method based on HF diffuse ultrasound at successive excitation amplitudes to characterize localized mechanical change induced by a heat-shock in a meterscale aluminum alloy slab. The major findings were:

(1) using CWI, a linear decrease in dv/v (relative velocity change) and a quadratic increase in kd (decorrelation) as a function of increasing source amplitude was observed. Thus, the parameters A dv/v and A kd are sensitive to localized mechanical properties to microstructural alterations.

(2) overall fatigue damage caused by plastic deformations varying from 6% to 10% in centimeter-scale high-manganese steel specimens, and instantaneous 400 o C heat-induced local mechanical change in meter-scale aluminum plate were successfully characterized by the A dv/v and A kd parameters.

(3) the observed amplitude dependence of HF ultrasound may be caused by nonlinear hysteresis mechanisms, and the observed spatial sensitivity of A dv/v and A kd could form the basis of an inverse problem for future imaging techniques.

The major advantages of the method used here over conventional approaches include: 1) significant reduction of the inspection time by comparing to the conventional monitoringoriented CWI method thanks to a simple and robust experimental setup; 2) high sensitivity to the material status in the early stages of damage, and to mechanical change; 3) compatibility between laboratory-based and on-site measurements; 4) with appropriate spatial sensitivity kernels, the method can not only be used to assess damage levels but also has great potential to image the material's status in the early stages of damage.

  in coda signals after one or several microstructural changes. Such propagation change due to local scattering change is denominated as microstructural change. The greater the kd, the larger the microstructural change(s).

  (a), each pair of ultrasonic transducers was glued to the bottom surface of each specimen at symmetrical locations. The two transducers serve as the emitter and the receiver, and were placed 15 cm apart to ensure strong multiple scattering. Thanks to the use of a high-voltage multiplexer (SSM-08, Ciprian), measurements with the centimeter-scale specimens could be collected simultaneously without any unnecessary interruption. The three specimens were therefore subjected to the same experimental protocol in identical environmental conditions. By defining the lowest amplitude signal as the reference, the eleven signals acquired from each specimen as the amplitude increased from 200 Vpp to 400 Vpp were analyzed by CWI. The amplitude-dependent parameters: A dv/v and A kd were then measured by applying the measurement procedures proposed in Section 3.2.

Figure. 1

 1 Figure. 1(b) and (c) illustrate the changes to dv/v and kd as a function of the Amp for specimen #2. A linear regression represents the velocity change (dv/v) yields A dv/v = -4.62 × 10 -4 per unit voltage amplitude. Simultaneously, a quadratic regression of the microstructural change (kd) yields A kd = 3.53 × 10 -5 per unit voltage amplitude (see Eq. 2).In Fig.2, the nonlinear response is plotted for the three steel specimens: (a) three A dv/v values of -4.48 × 10 -4 (#1), -4.62 × 10 -4 (#2) and -4.72 × 10 -4 (#3) per unit voltage amplitude were found; (b) three A kd values of 1.31 × 10 -5 (#1), 3.53 × 10 -5 (#2) and 5.78 × 10 -5 (#3) per unit excitation voltage amplitude were found.

Figure 3 .

 3 Figure 3. CWI detects mechanical change in a meter-scale aluminum slab. (a) Sample geometry, data acquisition system and transducers setup for a 20 mm thick meter-scale aluminum alloy slab. The black transducers labeled 1 to 8 are receivers, and the red transducer is the source. The surface of the plate, in the region marked by the red star, was heated to 400 oC. Diffuse waveforms recorded from receiver #8 in the intact state (b) and after 400 oC heat-shock (c). The black lines were recorded at 200 Vpp; the red lines were recorded at 400 Vpp. The insets show the details of the waveforms around the first waves detected (top left inset) and in the late coda (top right inset). The time window for CWI analysis is indicated by the gray zone on the graph.

  )). The two waveforms were almost identical within the early time window (top left inset of Fig.3(b)-(c)). In contrast, compared to the intact state (top right inset of Fig.3(b)), a more distinct phase shift in combination with waveform dissimilarity was clearly observed in the much later time window in the state after heat-shock (top right inset of Fig.3 (c)). This observation demonstrates a more significant apparent relative velocity and waveform dissimilarity upon high-level excitation following exposure to high-temperature, with the effect probably related to the local mechanical change created between the two states.

Figure 6 .

 6 Figure 6. Adv/v and Akd acquired at the eight transducers for the intact aluminum plate (dark bars) and following heatinduced mechanical change (light bars).

Funding

The authors acknowledge funding from the National Natural Science Foundation of China (Grant number:41874061,51738001,51779061), Public Science and Technology Research Funds Project of Ministry of Land and Resources of China (201511037-02), from Labex OSUG@2020 and from the University Grenoble Alpes IDEX.

Disclosure statement

The author(s) have no potential conflicts of interest to declare with respect to the research, authorship, and/or publication of this article.


Nicolas Audureau

Clémence Veith

Fanny Coumes

Thi Phuong

Thu Nguyen

Jutta Rieger
email: jutta.rieger@sorbonne-universite.fr

François Stoffelbach
email: francois.stoffelbach@sorbonne-universite.fr

RAFT-polymerized N-cyanomethylacrylamide-based (co)polymers exhibiting tunable UCST behavior in water

In this present work, we report the synthesis of a new family of UCST-thermoresponsive polymers based on Ncyanomethylacrylamide (CMAm). We demonstrate that the thermally-initiated reversible addition fragmentation chain transfer (RAFT) polymerization of CMAm conducted in DMF is well controlled. The homopolymer presents a sharp and reversible UCST-type phase transition in pure water with a very small hysteresis between cooling and heating cycles. We demonstrate that the cloud point (TCP) of PCMAm is strongly molar mass dependent and shifts towards lower temperatures in saline water. Moreover, the transition temperature can be tuned over a large temperature range by copolymerization of CMAm with acrylamide or acrylic acid. The latter copolymers are both thermo-and pH-responsive. Interestingly, by this strategy sharp and reversible UCST-type transitions close to physiological temperature can be reached, which makes the copolymers extremely interesting candidates for biomedical applications.

___________________________

Over the last decades, water-soluble thermosensitive polymers, presenting an upper critical solution temperature (UCST) in water have been the subject of extensive research in polymer science because they can be used for various applications, especially in the biomedical field. [START_REF] Seuring | Polymers with Upper Critical Solution Temperature in Aqueous Solution[END_REF][START_REF] Seuring | Polymers with Upper Critical Solution Temperature in Aqueous Solution: Unexpected Properties from Known Building Blocks[END_REF] They present a globule-to-coil conformation transition upon temperature increase in aqueous solution, meaning that they are insoluble below and soluble above a critical temperature. There are two classes of polymers exhibiting a UCST-type transition in water: ionic polymers, such as some polysulfobetaines [START_REF] Rajan | Tunable Dual-Thermoresponsive Core-Shell Nanogels Exhibiting UCST and LCST Behavior[END_REF][START_REF] Han | Reversible Thermoresponsive Plasmonic Core-Satellite Nanostructures That Exhibit Both Expansion and Contraction (UCST and LCST)[END_REF][START_REF] Fu | UCST-Type Thermosensitive Hairy Nanogels Synthesized by RAFT Polymerization-Induced Self-Assembly[END_REF][START_REF] Woodfield | Hydrophobically Modified Sulfobetaine Copolymers with Tunable Aqueous UCST through Postpolymerization Modification of Poly(pentafluorophenyl acrylate)[END_REF] or polycarboxybetaines [START_REF] Maji | Dual-Stimuli-Responsive L-Serine-Based Zwitterionic UCST-Type Polymer with Tunable Thermosensitivity[END_REF] , and neutral polymers. Among the latter family, only few homopolymers present an UCST in pure water suitable for applications: poly(Nacryloylglycinamide) [START_REF] Seuring | Non-Ionic Homo-and Copolymers with H-Donor and H-Acceptor Units with an UCST in Water[END_REF][START_REF] Seuring | Upper Critical Solution Temperature of Poly(N-acryloyl glycinamide) in Water: A Concealed Property[END_REF] (PNAGA) and its derivatives such as poly(N-acryloylasparaginamide) (PNAAAm) 10,[START_REF] Glatzel | Well-Defined Uncharged Polymers with a Sharp UCST in Water and in Physiological Milieu[END_REF] , poly(6-acryloyloxymethyluracil) [START_REF] Aoki | Adenosine-Induced Changes of the Phase Transition of Poly(6-(acryloyloxymethyl)uracil) Aqueous Solution[END_REF] , poly(N-acryloyl-nipecotamide) (PNANAm) [START_REF] Akiyama | Synthesis of Temperature-Responsive Polymers Containing Piperidine Carboxamide and N,Ndiethylcarbamoly Piperidine Moiety via RAFT Polymerization[END_REF] and poly(methacrylamide) (PMAm) [START_REF] Seuring | First Example of a Universal and Cost-Effective Approach: Polymers with Tunable Upper Critical Solution Temperature in Water and Electrolyte Solution[END_REF] . In contrast, polyacrylamide (PAm) has a theoretical UCST below 0 °C in water [START_REF] Seuring | First Example of a Universal and Cost-Effective Approach: Polymers with Tunable Upper Critical Solution Temperature in Water and Electrolyte Solution[END_REF][START_REF] Zhao | Rational Design of Thermoresponsive Polymers in Aqueous Solutions: A Thermodynamics Map[END_REF] , which can be increased by copolymerization of acrylamide (Am) with a hydrophobic comonomer such as styrene [START_REF] Pineda-Contreras | Importance of Compositional Homogeneity of Macromolecular Chains for UCST-type Transitions in Water: Controlled Versus Conventional Radical Polymerization[END_REF] or acrylonitrile (AN). [START_REF] Seuring | First Example of a Universal and Cost-Effective Approach: Polymers with Tunable Upper Critical Solution Temperature in Water and Electrolyte Solution[END_REF][START_REF] Asadujjaman | Phase transition and aggregation behaviour of an UCST-type copolymer poly(acrylamide-co-acrylonitrile) in water: effect of acrylonitrile content, concentration in solution, copolymer chain length and presence of electrolyte[END_REF][START_REF] Otsuka | Fluorescent Labeling Method Re-Evaluates the Intriguing Thermoresponsive Behavior poly(acrylamide-coacrylonitrile)s with Upper Critical Solution Temperatures[END_REF] The resulting statistical copolymer P(Am-co-AN) is one of the most studied neutral UCST copolymers and used in many applications, in particular for drug delivery. [START_REF] Zha | Stimulus responsive nanogels for drug delivery[END_REF][START_REF] Li | Antitumor Drug Delivery Modulated by A Polymeric Micelle with an Upper Critical Solution Temperature[END_REF] It is generally obtained by free radical polymerization (FRP) or reversible deactivation radical polymerization (RDRP) -in particular through reversible addition fragmentation chain transfer (RAFT) -of Am and AN in organic solvents [START_REF] Seuring | First Example of a Universal and Cost-Effective Approach: Polymers with Tunable Upper Critical Solution Temperature in Water and Electrolyte Solution[END_REF] or in water [START_REF] Audureau | Thermoresponsive properties of poly(acrylamide-co-acrylonitrile)-based diblock copolymers synthesized (by PISA) in water[END_REF] . Uchiyama and Otsuka et al. [START_REF] Otsuka | Fluorescent Labeling Method Re-Evaluates the Intriguing Thermoresponsive Behavior poly(acrylamide-coacrylonitrile)s with Upper Critical Solution Temperatures[END_REF] reported that -in addition to hydrogen bonds between the Am units [START_REF] Seuring | First Example of a Universal and Cost-Effective Approach: Polymers with Tunable Upper Critical Solution Temperature in Water and Electrolyte Solution[END_REF][START_REF] Hou | Understanding the UCST-type transition of P(AAm-co-AN) in H2O and D2O: dramatic effects of solvent isotopes[END_REF] dipole-dipole interactions between the cyano groups in the AN units are a major driving force for the UCST behavior. Due to a difference in reactivity of both comonomers [START_REF] Chapiro | Influence des solvants sur la copolymerisation de l'acrylamide avec l'acrylonitrile[END_REF] , the Am/AN composition and distribution in the polymer chains depend however greatly on the polymerization technique, and therefore the cloud point (TCP) is sensitive to the polymerization conditions. [START_REF] Otsuka | Fluorescent Labeling Method Re-Evaluates the Intriguing Thermoresponsive Behavior poly(acrylamide-coacrylonitrile)s with Upper Critical Solution Temperatures[END_REF] It was also reported that the content of AN in the polymer P(Amco-AN) was inferior to the content of AN in the feed, because part of the AN monomer can be easily lost by evaporation during the removal of dissolved oxygen before radical polymerization. [START_REF] Otsuka | Fluorescent Labeling Method Re-Evaluates the Intriguing Thermoresponsive Behavior poly(acrylamide-coacrylonitrile)s with Upper Critical Solution Temperatures[END_REF] To overcome these issues, we propose herein a much more robust and simple strategy relying on one single monomer, namely Ncyanomethyacrylamide (CMAm). CMAm combines the functional groups of P(Am-co-AN), and we postulated that PCMAm might be a promising candidate to prepare a novel family of UCST-type (co)polymers.

Importantly, the synthesis of the monomer is very straightforward. Moreover, it has the advantage of being solid at room temperature, therefore being handled more easily compared to AN. To the best of our knowledge, only one publication [START_REF] Choi | Volume Phase Transition Behavior of N-Isopropyl Acrylamide-N-Cyanomethyl Acrylamide Copolymer Gel Particles: The Effect of Crosslinking Density[END_REF] mentions the use of this monomer for the preparation of submicron-sized Nisopropylacrylamide/CMAm copolymer gel particles. The homopolymer itself has never been studied.

Here, we report for the first time the homopolymerization of CMAm by FRP and RAFT-RDRP. Furthermore, we study systematically the thermoresponsive behavior of the resulting homopolymers by turbidimetry. In particular, we evaluate the impact of the number-average degree of polymerization (DPn) and demonstrate the possibility to fine-tune the transition temperature by the addition of hydrophilic comonomers within the polymer chains.

The CMAm monomer was readily obtained in one-step, by amidification of acryloyl chloride with aminoacetonitrile in the presence of NaOH following a reported procedure (see S.I. and Figure S1). [START_REF] Choi | Volume Phase Transition Behavior of N-Isopropyl Acrylamide-N-Cyanomethyl Acrylamide Copolymer Gel Particles: The Effect of Crosslinking Density[END_REF] We firstly investigated its ability to be radically homopolymerized in a controlled fashion by RAFT in DMF solution, using ethyl 2-(butylthiocarbonothioylthio)propanoate (see S.I. and Figure S2), a trithiocarbonate-type chain transfer agent (CTA) well-known to control the polymerization of acrylamides (Scheme 1). Not only the transfer agent but also the initiator (2,2'-azobis(2-methylproprionitrile), AIBN) was chosen nonionic in order to avoid any possible effect of the chain end on the thermoresponsive behavior. [START_REF] Seuring | Upper Critical Solution Temperature of Poly(N-acryloyl glycinamide) in Water: A Concealed Property[END_REF][START_REF] Akiyama | Synthesis of Temperature-Responsive Polymers Containing Piperidine Carboxamide and N,Ndiethylcarbamoly Piperidine Moiety via RAFT Polymerization[END_REF] Figure S3 shows the monomer conversion versus time for the homopolymerization of CMAm under RAFT conditions (Experiment P4 in Table 1).

Scheme 1. Synthesis route for PCMAm polymers via RAFT polymerization.

The same procedure was used for the FRP in DMF except that no RAFT agent was added (P6 in Table 1 and Figure S4). As shown in Figure S5 and resumed in Table 1, the thermally-initiated RAFT polymerization of CMAm conducted in DMF was well controlled as the polymers displayed a dispersity (Đ = Mw/Mn) below 1.5 and the SEC chromatograms evolved toward higher molar masses by targeting higher DPn. The efficiency of the transfer reaction was also confirmed by [START_REF] Seuring | Polymers with Upper Critical Solution Temperature in Aqueous Solution[END_REF] H NMR (Figure S6) and by SEC equipped with an in-line UV detector. Indeed, SEC chromatogram (Figure S7) obtained with the UV detector at 309 nm shows the presence of the trithiocarbonate functionality, which strongly absorbs at this wavelength. 25 Thermal analysis by differential scanning calorimetry and thermogravimetry were performed on the homopolymer obtained by FRP (P6, Table 1) showing respectively a glass transition temperature of 200 °C and a thermal degradation at about 250 °C (Figure S8). a Determined by 1 H NMR analysis. b Theoretical number-average degree of polymerization, DPn,th, and number-average molar mass, Mn,th, calculated using the experimental conversions. c Determined by 1 H NMR spectroscopy in DMSO-d6 using the relative integration of the chain end and the monomer units (an example is shown in Figure S6 for P2). d Numberaverage molar mass, Mn, and dispersity, Ð, determined by SEC in DMF (+ LiBr 1g L -1 ) with a PMMA calibration. e Determined in water by turbidimetry at 0.5 wt%, on 1 st cooling/2 nd heating.

The thermoresponsive solution properties of the new homopolymer were examined by turbidimetry. A typical UCST-type thermoresponsive behavior with a sharp transition was observed for PCMAm with DPn between 21 and 73: polymers were insoluble and precipitated in pure water at low temperatures, whereas they were soluble at high temperatures. Figure 1 shows that the UCST-type transition temperature increases with the DPn in the range 21-56 from 54 to 80 °C (measured at the first cooling at 0.5 wt%). For higher DPns, the transition temperatures change only slightly. The highest molar mass polymer studied, with DPn = 183 (PCMAm183, P5 in Table 1), stayed turbid up to 90 °C, but demonstrated the beginning of a transition > 90 °C. This decrease in solubility with increasing chain length is thermodynamically expected and was previously described for other UCST-type homopolymers such as PNAAAm 11 or PNANAm [START_REF] Akiyama | Synthesis of Temperature-Responsive Polymers Containing Piperidine Carboxamide and N,Ndiethylcarbamoly Piperidine Moiety via RAFT Polymerization[END_REF] . As expected, the PCMAm obtained by FRP (P6 in Table 1) with the highest number-average molar mass (Mn) was insoluble between 20 to 90 °C at 0.5 wt% in pure water (Figure 1A) and did not show any thermoresponsive behavior. 1) and PCMAm73 (P4, Table 1) (solid lines) in water and in PBS (dashed lines) (B) at 0.5 wt%.

All polymers showed an excellent reversibility of phase transition as shown in Figure S9 for sample P3.

Interestingly, the turbidity measurements showed a very small hysteresis, unlike other UCST homopolymers, such as PNAGA [START_REF] Seuring | Upper Critical Solution Temperature of Poly(N-acryloyl glycinamide) in Water: A Concealed Property[END_REF] , PNANAm [START_REF] Akiyama | Synthesis of Temperature-Responsive Polymers Containing Piperidine Carboxamide and N,Ndiethylcarbamoly Piperidine Moiety via RAFT Polymerization[END_REF] or PMAm [START_REF] Käfer | Tuning the Phase Transition from UCST-Type to LCST-Type by Composition Variation of Polymethacrylamide Polymers[END_REF] . We also investigated the impact of polymer concentration on the phase transition behavior of PCMAm. The turbidity curves of sample P3 at 0.25, 0.5 and 1 wt% in Figure S10 show actually that the TCP of PCMAm varies only very slightly in the studied concentration range. Moreover, PCMAm retained its thermoresponsiveness in phosphate buffered saline (PBS), but the TCP shifted towards significantly lower temperatures (Figure 1B), in accordance with previous results observed for PNAGA [START_REF] Liu | Atom transfer radical polymerization as a tool for making poly(Nacryloylglycinamide) with molar mass independent UCST-type transitions in water and electrolytes[END_REF] . For instance, the TCP for sample P4 with DPn = 73 decreased from 85 °C in pure water towards 63 °C in PBS.

Finally, to investigate the influence of the NaCl concentration on the thermoresponsiveness of PCMAm, turbidimetry measurements of PCMAm51 aqueous solutions at 0.5 wt% were done at increasing concentrations of NaCl. As shown in Figure S11, the TCP is gradually decreased from ~80 to ~67 °C for increasing concentrations of NaCl (up to 0.5 M). * This tendency was also observed for PNAGA by Agarwal et al. [START_REF] Liu | Atom transfer radical polymerization as a tool for making poly(Nacryloylglycinamide) with molar mass independent UCST-type transitions in water and electrolytes[END_REF] and for P(Am-co-AN) by Uchiyama and Otsuka et al. [START_REF] Otsuka | Fluorescent Labeling Method Re-Evaluates the Intriguing Thermoresponsive Behavior poly(acrylamide-coacrylonitrile)s with Upper Critical Solution Temperatures[END_REF] .

Despite the sharp and reversible transition, the application of PCMAm in the biomedical field might be limited by the relatively high TCP, generally above 50 °C. Therefore, we decided to introduce hydrophilic comonomers, namely acrylamide (Am), and acrylic acid (AA), into the polymer in order to fine-tune the transition temperature. The controlled radical copolymerization of CMAm with Am or AA was performed in DMF at 35 °C in presence of the same RAFT agent and V-70 as a non-ionic radical initiator (Scheme S1). First, two series of statistical copolymers with CMAm and Am were synthesized with various feed ratios (percentage of Am ranging from 9 to 30 mol%, Table 2) keeping constant the total monomer concentration at 25 wt%, and targeting either DPn = 50 or 100. Kinetic monitoring during the polymerizations carried out by [START_REF] Seuring | Polymers with Upper Critical Solution Temperature in Aqueous Solution[END_REF] H NMR showed that the copolymerizations proceeded without significant variation of the copolymer composition (Figure S12). Indeed, the calculated molar percentages of Am in the copolymers determined by 1 H NMR at any conversion remained close to the initial ones (final values given in Table 2). This suggests a very similar reactivity of both monomers and reactivity ratios close to one. After purification by precipitation in chloroform, the copolymers were * It should be noted that the observed slight increase of transmittance at low temperature might be attributed to a macroscopic phase separation, as the polymer precipitates out of the solution leading to a higher transmittance compared to temperatures close to TCP where the polymer gradually dissolves. characterized by SEC and 1 H NMR (Table 2 and Figures S13A andS14). Generally, polymerization control was reached for all compositions; lower molar mass dispersities (Đ < 1.4) were obtained when shorter polymers were targeted, presumably because they were synthesized in shorter reaction times. In addition, the molar fraction of Am in the copolymers determined by [START_REF] Seuring | Polymers with Upper Critical Solution Temperature in Aqueous Solution[END_REF] H NMR (Fx, Table 2) was very close to the initial molar fraction of Am in the feed, hinting at a random copolymerization mechanism. X represents the comonomer (Am or AA) and M represents both comonomers. a Initial mol% of X in the mixture of monomers.

b Overall monomer conversion determined by 1 H NMR analysis. c mol% of X in the copolymer deduced from 1 H NMR analysis from the individual molar conversions of X (see SI). d Molar fraction of X in the purified copolymer deduced from 1 H NMR analysis (see SI). e Theoretical number-average degree of polymerization, DPn,th, and number-average molar mass, Mn,th, calculated using the experimental conversions. f Determined by 1 H NMR spectroscopy in DMSO-d6 using the relative integration of the chain end and the monomer units. g Number-average molar mass, Mn, and dispersity, Ð, determined by SEC in DMF (+ LiBr 1g L -1 ) with a PMMA calibration. h Determined in water by turbidimetry at 0.5 wt%, on 1 st cooling/2 nd heating.

The thermoresponsiveness of the P(CMAm-co-Am) copolymers in water at 0.5 wt% was then investigated by turbidimetry (Table 2 and Figure 2A). In all cases, the thermal response of the copolymer solutions was sharp and reversible with a very small hysteresis (≤ 5 °C, see Table 2) during the cooling and the heating cycle. As summarized in Table 2 and presented in Figure 2A, the TCP decreased with increasing the hydrophilic monomer content in the copolymer, as expected. [START_REF] Seuring | Non-Ionic Homo-and Copolymers with H-Donor and H-Acceptor Units with an UCST in Water[END_REF][START_REF] Lu | Small dop of comonomer, giant shift of cloud point: Thermo-responsive behavior and mechanism of poly(methylacrylamide) copolymers with an upper critical solution temperature[END_REF] Figure 2. Turbidity curves (cooling step) of P(CMAm-co-Am)x (A) and P(CMAm-co-AA)x (B) (Table 2) at 0.5 wt% in water.

Interestingly, P(CMAm-co-Am) copolymers with a DPn, ~ 50 exhibited a thermoresponsive transition which was tunable by the Am content over a huge temperature range, between 22 and 80 °C. When the DP of the copolymer was doubled keeping constant the comonomer content, a significant increase in the TCP was observed, similar to the PCMAm homopolymer. For instance, comparing the copolymers P10 and P13 (with Am content ~ 26 mol%) we can observe an increase in the TCP of 18 °C.

In the second series, AA was tested as a comonomer. Acrylic acid contains a carboxylic acid moiety, which could provide a pH-dependent thermosensitive behavior to AA-containing PCMAm-based copolymers. A series of statistical copolymers were synthesized varying the comonomer feed ratio (Table 2), while keeping constant the total monomer concentration at 25 wt%. The mol% of AA in the monomer feed was varied from 14 to 41% in order to tune the copolymer composition. As reported in Table 2, the molar percentages of AA in the copolymers determined by [START_REF] Seuring | Polymers with Upper Critical Solution Temperature in Aqueous Solution[END_REF] H NMR remained close to the initial ones indicating again a very similar reactivity of both monomers. After purification by precipitation and successful methylation [START_REF] Velasquez | Poly(vinylidene chloride)-Based Amphiphilic Block Copolymers[END_REF] of the carboxylic acid groups (yielding methyl acrylate units), the molar masses of the final samples were determined by SEC (Table 2 and

Figure S13B

). Symmetric and narrow molar mass distributions were obtained (Đ < 1.3) in all cases. The thermoresponsiveness of the P(CMAm-co-AA) copolymers in water at 0.5 wt% was then investigated by turbidimetry (Figure 2B). For all copolymers, the thermal response of the solutions was sharp and reversible with a slight hysteresis (≤ 6 °C, Table 2) between the cooling curve and the heating curve. Again, the TCP decreased with increasing AA content, and at constant AA content, it was higher for longer copolymer lengths.

For instance, by comparing the copolymers P16 and P18 in Table 2 with the same AA content (~25 mol%), we can observe an increase of the TCP by 20 °C. Interestingly, for both comonomers, the TCP decreases almost linearly with the comonomer content as shown in Figure 3 Black squares: X = Am (P3 in Table 1 and P8-P10 in Table 2). Red circles: X = AA (P3 in Table 1 and P14-P17 in Table 2).

As acrylic acid monomer units in the P(CMAm-co-AA) copolymers are pH sensitive, the impact of the degree of ionization of the acid units was studied on copolymer P16 by varying the pH of the medium at which the turbidity measurements were performed. While this copolymer was soluble at pH = 5.7 (no thermosensitive behavior was observed), a TCP of 35 °C was observed at natural pH (3.7) (cooling step) which increased to 40 °C at pH = 2.0 (Figure S16). It is therefore possible to adjust the solubility and transition temperature of P(CMAm-co-AA) by modifying the pH of the aqueous solution, in which it is dissolved.

Finally, we also investigated the impact of polymer concentration on the phase transition behavior of P(CMAmco-X) copolymers (with X = Am or AA). The turbidity curves of samples P10 (P(CMAm0.75-co-Am0.25)57) and P16 (P(CMAm0.72-co-AA0.28)47) at 0.25, 0.5 and 1 wt% in Figure S17 show actually that the TCP of the copolymers is more sensitive to the concentration than that of the homopolymer (Figure S10), at least in the studied concentration range. Indeed, for both copolymers P10 and P16 (with FX ~0.26), the TCP decreased by around 25 °C when the copolymer concentration was decreased from 1 to 0.25 %wt, whereas the TCP of the homopolymer decreased in the same conditions by less than 5 °C.

In conclusion, new UCST-type thermosensitive PCMAm homopolymers and P(CMAm-co-X) statistical copolymers (with X = Am or AA) of various compositions have been synthesized for the first time, in a controlled fashion by RAFT polymerization. PCMAm homopolymers exhibit a sharp and reversible UCSTtype thermal transition in pure water between 54 °C and 85 °C depending on the degree of polymerization, with a very small hysteresis between the cloud point upon cooling and heating. The transition temperature was tuned by the insertion of hydrophilic comonomer units, notably Am and AA. For instances, with a low amount of acrylamide (≤ 27 mol%) the TCP could be tuned over a huge temperature range, from ~20 to 85 °C. Compared to well-studied P(Am-co-AN) copolymers, for the TCP can also be tuned by the copolymer composition, CMAm is much easier to handle than AN, because CMAm is a solid monomer at room temperature. In addition, its copolymerization with Am (or AA) in DMF appears random avoiding thus a gradual change of composition over the polymer chain during RDRP, or the formation of a mixture of polymer chains with different compositions during FRP. Furthermore, the copolymer comporting AA units was not only responsive to temperature but also to pH. We believe that these new (co)polymers pave the way towards a new class of responsive materials, and their sharp and reversible transition temperatures adjustable to physiological temperature makes the copolymers extremely interesting candidates for biomedical applications.

  Polymerizations were performed at 70 °C in presence of a RAFT agent (CTA) using AIBN as a radical initiator at an initial molar ratio of CTA/AIBN: 1/0.1-0.2. *The polymerization was performed at 35 °C in presence of V-70 as a radical initiator. **Free radical polymerization (without RAFT agent) at an initial molar ratio of CMAm/AIBN: 200/1.

Figure 1 .

 1 Figure 1. Turbidity curves (first cooling) of PCMAm polymers with various DPn at 0.5 wt% in water (A) and

  and Figure S15. Strong interactions between the hydrophilic comonomer and water should explain why the solubilization is favored and occurs at lower temperatures as the proportion of comonomer increases.

Figure 3 .

 3 Figure 3. Evolution of TCP (cooling step) versus the mol% of comonomer in the P(CMAm-co-X)s of DPn ~ 50.Black squares: X = Am (P3 in Table1and P8-P10 in Table2). Red circles: X = AA (P3 in Table1and P14-P17 in Table2).

Table 1 .

 1 Experimental conditions and results for the RAFT-mediated polymerizations of CMAm performed at 20 wt% in DMF #

	Entry	[CMAm]0 / [CTA]0	Time (min)	Conv a (%)	DPn,th b	DPn,exp c	Mn,th b (kg mol -1 )	Mn,SEC d (kg mol -1 )	Đ d	TCP e (°C)
	P1	20/1	100	76	15	21	1.9	4.7	1.21	54/54
	P2*	41/1	300	69	28	28	3.3	7.6	1.17	61/58
	P3	60/1	280	85	51	56	5.9	11.5	1.26	80/79
	P4	115/1	243	62	71	73	8.1	14.8	1.27	85/84
	P5	230/1	360	82	189	183	21.1	22.2	1.47	>90
	P6**	-	76	83	-	-	-	52.1	2.24	>90
	#

Table 2 .

 2 Experimental conditions for the synthesis of P(CMAm-co-X) copolymers (with X = Am or AA) in the presence of CTA and their molecular characteristics #

	Entry X	mol% of X a	[M]0/ [CTA]0	Time (h)	Conv. b (mol%)	mol% of X c

FX d DPn,th e DPn,exp f Mn,th e

											(kg mol -1 )	Mn,SEC g (kg mol -1 )	Đ g	TCP h (°C)
	P7	-	0	161/1	3.0	68	0	0	109	113	12.4	18.9	1.37	85/- †
	P8		9	100/1	4.0	56	9	0.08	56	60	6.2	10.8	1.27	67/67
	P9		19	100/1	3.7	57	18	0.15	58	61	6.2	10.7	1.26	37/40
	P10	Am	30	100/1	5.3	53	28	0.25	53	57	5.5	9.1	1.37	22/27
	P11		9	140/1	14.8	64	8	0.06	90	102	9.9	17.9	1.47	77/80
	P12		20	152/1	6.8	66	20	0.18	101	111	10.6	17.7	1.55	65/68
	P13		30	147/1	6.8	68	28	0.27	100	106	10.2	16.3	1.38	40/44
	P14		14	100/1	5.0	56	14	0.13	56	59	6.1	13.8	1.15	55/59
	P15		21	97/1	6.2	54	22	0.20	52	56	5.6	11.3	1.27	53/55
	P16	AA	26	88/1	2.3	48	28	0.28	43	47	4.4	10.0	1.14	35/40
	P17		41	103/1	2.0	49	43	0.40	50	52	5.0	10.1	1.17	18/24
	P18		24	153/1	5.2	65	26	0.23	100	96	10.3	19.9	1.26	55/57
	P19		37	141/1	5.0	66	39	0.38	93	97	9.1	18.6	1.08	28/32

# Polymerizations were performed in DMF at 35 °C in presence of a RAFT agent (CTA) and V-70 as a radical initiator at 25 wt%.

Zhang, W.; D'Agosto, F.; Dugas, P.-Y. Y.; Rieger, J.; Charleux, B. RAFT-mediated one-pot aqueous

Supporting Information

Experimental details and supplementary data.