Laurent Delbreilh

Molecular motions in functional self-assembled nanostructures.

The construction of “smart” materials able to perform specific functions at the molecular scale through the application of various stimuli is highly attractive but still challenging. The most recent applications indicate that the outstanding flexibility of self-assembled architectures can be employed as a powerful tool for the development of innovative molecular devices, functional surfaces and smart nanomaterials. Structural flexibility of these materials is known to be conferred by weak intermolecular forces involved in self-assembly strategies. However, some fundamental mechanisms responsible for conformational lability remain unexplored. Furthermore, the role played by stronger bonds, such as coordination, ionic and covalent bonding, is sometimes neglected while they can be employed readily to produce mechanically robust but also chemically reversible structures. In this review, recent applications of structural flexibility and molecular motions in self-assembled nanostructures are discussed. Special focus is given to advanced materials exhibiting significant performance changes after an external stimulus is applied, such as light exposure, pH variation, heat treatment or electromagnetic field. The crucial role played by strong intra- and weak intermolecular interactions on structural lability and responsiveness is highlighted.

Combining Flash DSC, DSC and broadband dielectric spectroscopy to determine fragility

New experimental results focused on Flash DSC, DSC and broadband dielectric spectroscopy investigations are reported in this work. The fictive temperatures and fragility indexes are estimated from Flash DSC experiments and compared to values obtained from classical DSC. The consistency of the Tool–Narayanaswamy–Moynihan model and fragility concept is then investigated over a large range of cooling rates. Indeed, the Flash DSC allows exploring thermal properties of materials over a continuous and broad range of heating and cooling rates, complementary to rates usually available with DSC. The reliability of investigations is also demonstrated by comparing results obtained from two model amorphous polymeric systems: polystyrene and poly(ethylene terephthalate)-glycol. The temperature dependence of the cooling rate obtained by Flash DSC and DSC is also compared to the temperature dependence of the relaxation times obtained from broadband dielectric spectroscopy, experiment considered as the reference concerning the fragility measurements. The comparison of these two dependencies implies a better understanding about the origin of the temperature dependence of the cooling rate.

Crystallization kinetics and molecular mobility of an amorphous active pharmaceutical ingredient: A case study with Biclotymol

The present case study focuses on the crystallization kinetics and molecular mobility of an amorphous mouth and throat drug namely Biclotymol, through differential scanning calorimetry (DSC), temperature resolved X-ray powder diffraction (TR-XRPD) and hot stage microscopy (HSM). Kinetics of crystallization above the glass transition through isothermal and non-isothermal cold crystallization were considered. Avrami model was used for isothermal crystallization process. Non-isothermal cold crystallization was investigated through Augis and Bennett model. Differences between crystallization processes have been ascribed to a site-saturated nucleation mechanism of the metastable form, confirmed by optical microscopy images. Regarding molecular mobility, a feature of molecular dynamics in glass-forming liquids as thermodynamic fragility index m was determined through calorimetric measurements. It turned out to be around m=100, describing Biclotymol as a fragile glass-former for Angells classification. Relatively long-term stability of amorphous Biclotymol above Tg was analyzed indirectly by calorimetric monitoring to evaluate thermodynamic parameters and crystallization behavior of glassy Biclotymol. Within eight months of storage above Tg (T=Tg+2°C), amorphous Biclotymol does not show a strong inclination to crystallize and forms a relatively stable glass. This case study, involving a multidisciplinary approach, points out the importance of continuing looking for stability predictors.

Transformation of an active pharmaceutical ingredient upon high-energy milling: A process-induced disorder in Biclotymol.

This study investigates for the first time the thermodynamic changes of Biclotymol upon high-energy milling at various levels of temperature above and below its glass transition temperature (Tg). Investigations have been carried out by temperature modulated differential scanning calorimetry (TM-DSC) and X-ray powder diffraction (XRPD). Results indicate that Biclotymol undergoes a solid-state amorphization upon milling at Tg-45 °C. It is shown that recrystallization of amorphous milled Biclotymol occurs below the glass transition temperature of Biclotymol (Tg=20 °C). This displays molecular mobility differences between milled Biclotymol and quenched liquid. A systematic study at several milling temperatures is performed and the implication of Tg in the solid-state transformations generally observed upon milling is discussed. Influence of analysis temperature with respect to interpretation of results was investigated. Finally, it is shown that co-milling Biclotymol with only 20 wt% of amorphous PVP allows a stable amorphous dispersion during at least 5 months of storage.

Molecular Relaxations in Supercooled Liquid and Glassy States of Amorphous Quinidine: Dielectric Spectroscopy and Density Functional Theory Approaches

In this article, we conduct a comprehensive molecular relaxation study of amorphous Quinidine above and below the glass-transition temperature (Tg) through broadband dielectric relaxation spectroscopy (BDS) experiments and theoretical density functional theory (DFT) calculations, as one major issue with the amorphous state of pharmaceuticals is life expectancy. These techniques enabled us to determine what kind of molecular motions are responsible, or not, for the devitrification of Quinidine. Parameters describing the complex molecular dynamics of amorphous Quinidine, such as Tg, the width of the α relaxation (βKWW), the temperature dependence of α-relaxation times (τα), the fragility index (m), and the apparent activation energy of secondary γ relaxation (Ea-γ), were characterized. Above Tg (> 60 °C), a medium degree of nonexponentiality (βKWW = 0.5) was evidenced. An intermediate value of the fragility index (m = 86) enabled us to consider Quinidine as a glass former of medium fragility. Below Tg (< 60 °C), one well-defined secondary γ relaxation, with an apparent activation energy of Ea-γ = 53.8 kJ/mol, was reported. From theoretical DFT calculations, we identified the most reactive part of Quinidine moieties through exploration of the potential energy surface. We evidenced that the clearly visible γ process has an intramolecular origin coming from the rotation of the CH(OH)C9H14N end group. An excess wing observed in amorphous Quinidine was found to be an unresolved Johari-Goldstein relaxation. These studies were supplemented by sub-Tg experimental evaluations of the life expectancy of amorphous Quinidine by X-ray powder diffraction and differential scanning calorimetry. We show that the difference between Tg and the onset temperature for crystallization, Tc, which is 30 K, is sufficiently large to avoid recrystallization of amorphous Quinidine during 16 months of storage under ambient conditions.

Quasi-isothermal and heat–cool protocols from MT-DSC

Abstract Understanding the evolution of the cooperative molecular mobility as a function of time and temperature remains an unsolved question in condensed matter physics. Many recent works concern the question of the molecular dynamic slowdown in a temperature domain ranging from the crossover temperature Tc (beginning of cooperative relaxation) down to the calorimetric glass transition temperature Tg. Recent studies have shown that the estimation of cooperativity length based on calorimetric investigations using Donth’s approach can be extended to a wider temperature range from Tg to Tc. To describe the relaxation time evolution and the characteristic length evolution of cooperative motions, besides the Donth’s fluctuation approach other models exist in the literature such as “4 points correlation function” model. Whatever the model used, calorimetric investigations are needed to estimate the heat capacity as a function of the temperature. In this work, we have focused our attention on the modulated temperature differential scanning calorimetry (MT-DSC) experiments and we have tested different MT-DSC protocols allowing the heat capacity determination. For this goal we decided to work on different amorphous glass formers in order to cover a large range of glass transition temperature. The influence of the protocol used on the cooperativity length calculation is discussed in detail. Lissajous figures were constructed to verify whether the steady state is reached.

Secondary Retardation/Relaxation Processes in Bisphenol A Polycarbonate: Thermostimulated Creep and Dynamic Mechanical Analysis Combined Investigations

Abstract Thermostimulated creep (TSCr) and dynamic mechanical analysis (DMA) have been used to analyze the complex secondary retardation/relaxationmode of bisphenol A polycarbonate (PC). TSCr and DMA studies have been combined to extend the frequency range using the very low equivalent frequency of TSCr measurement (≈ 10−3 Hz). The dielectric spectra revealed a bimodal β retardation/relaxation mode with two overlapped components β2 and β1. A thermal sampling (TS) protocol has been applied to TSCr measurements to obtain this β1 mode fine structure. TSCr has proved to be a powerful tool to analyze the two overlapped contributions.

Insights on the Physical State Reached by an Active Pharmaceutical Ingredient upon High-Energy Milling

We study the physicochemical transformations of crystalline quinidine upon high-energy milling. The investigations have been achieved by classical, high performance, and fast scanning calorimetry combined with broadband dielectric spectroscopy and X-ray powder diffraction. As evolution of crystalline quinidine with time of milling revealed a prominent sub-Tg cold-crystallization phenomenon, independent and complementary analytical techniques were implemented. Fast scanning calorimetry was performed for the first time on a milled pharmaceutical compound to postpone the crystallization event to higher temperatures. These fast thermal analyses allowed one to spotlight a genuine glass transition event. In addition, an aging experiment on the milled powder revealed a clear structural relaxation testifying to the presence of a glassy fraction in the milled sample. Last, dielectric analysis of milled quinidine disclosed the presence of localized and delocalized molecular mobility characteristics of glasses. Results for samples obtained by two distinct amorphization routes, vitrification and high-energy milling, indicate that amorphous fraction in milled quinidine behaves the same way as melt-quenched quinidine. These above-mentioned techniques proved their relevancy and efficiency to characterize milled quinidine, and fast scanning calorimetry in particular appears a promising screening tool for disordered systems.

Thermal growth of organic supramolecular crystals with screw dislocations

We report here a simple pathway to thermally assemble acene-based molecules into large crystals without modification of their chemical structures. Differential scanning calorimetry was used to characterize properly thermal events occurring during successive heating and cooling processes. More interestingly, observations by means of polarized light microscopy (POM) revealed that a spontaneous formation of screw dislocations within crystals during the isothermal treatment triggered a structural reorganization by forming large and well-defined spiral architectures. After this reorganization, new crystals showed an excellent ordering in both vertical and horizontal directions. Due to the richness in pi-electrons of acene-based molecules, we expect this work of importance to organic electronics, especially in the design of new molecular building blocks and investigation of their assembly into sophisticated supramolecular structures.

Rock permittivity characterization and application of electromagnetic mixing models for density/compactness assessment of HMA by means of step-frequency radar

This work aims to determine the compactness/density of hot mix asphalt by measuring its permittivity by means of step-frequency radar. As hot mix asphalt is mainly made of rocks; their dielectric properties are measured in the frequency range of 0.5 - 4 Ghz with step-frequency radar, using cylindrical cavities. The results show that the rocks can be considered as low-loss dielectric. As electromagnetic mixing models are required to translate measured permittivity to the compactness, power law models and unified mixing rules are needed for laboratory experimental data. The slab permittivity of various compactness is determined with the help of the step-frequency radar system. This study shows that: (i) the selection of the electromagnetic mixing model has a critical impact on the accuracy of the calculated compactness; (ii) the choice of the host matrix for a family of unified mixing rules has huge consequences; and (iii) the best assessment of compactness/density is given by the complex refractive index model and Rayleigh and Bottcher models with an aggregate matrix.