System for control of polarization state of light and generation of light with continuously rotating linear polarization.

We present a technique for generating light in an arbitrary polarization state. The technique is based on interference of two orthogonally polarized light beams, whose amplitudes and phases are controlled with a Mach-Zehnder inteferometer with acousto-optic modulators (AOMs) placed in each arm. We demonstrate that via control over amplitudes, phases, and frequencies of acoustic waves driving the AOMs, any polarization state can be synthesized. In particular, we demonstrate generation of linearly polarized light, whose polarization plane continuously rotates at a rate from 1 kHz to 1 MHz. Such light finds applications in science (e.g., investigations of Bloch-Siegert effect) and technology (optically pumped magnetometers).

Experimental evidence of high pressure decoupling between charge transport and structural dynamics in a protic ionic glass-former.

In this paper the relaxation dynamics of ionic glass-former acebutolol hydrochloride (ACB-HCl) is studied as a function of temperature and pressure by using dynamic light scattering and broadband dielectric spectroscopy. These unique experimental data provide the first direct evidence that the decoupling between the charge transport and structural relaxation exists in proton conductors over a wide T-P thermodynamic space, with the time scale of structural relaxation being constant at the liquid-glass transition (τα = 1000 s). We demonstrate that the enhanced proton transport, being a combination of intermolecular H+ hopping between cation and anion as well as tautomerization process within amide moiety of ACB molecule, results in a breakdown of the Stokes-Einstein relation at ambient and elevated pressure with the fractional exponent k being pressure dependent. The dT g /dP coefficient, stretching exponent ßKWW and dynamic modulus E a /ΔV # were found to be the same regardless of the relaxation processes studied. This is in contrast to the apparent activation volume parameter that is different when charge transport and structural dynamics are considered. These experimental results together with theoretical considerations create new ideas to design efficient proton conductors for potential electrochemical applications.

Studying the Impact of Modified Saccharides on the Molecular Dynamics and Crystallization Tendencies of Model API Nifedipine.

Molecular dynamics of pure nifedipine and its solid dispersions with modified carbohydrates as well as the crystallization kinetics of active pharmaceutical ingredient (API) above and below the glass transition temperature were studied in detail by means of broadband dielectric spectroscopy (BDS), differential scanning calorimetry (DSC), and X-ray diffraction method. It was found that the activation barrier of crystallization increases in molecular dispersions composed of acetylated disaccharides, whereas it slightly decreases in those consisting of modified monocarbohydrates for the experiments carried out above the glass transition temperature. As shown by molecular dynamics simulations it can be related to the strength, character, and structure of intermolecular interactions between API and saccharides, which vary dependently on the excipient. Long-term physical stability studies showed that, in solid dispersions consisting of acetylated maltose and acetylated sucrose, the crystallization of nifedipine is dramatically slowed down, although it is still observable for a low concentration of excipients. With increasing content of modified carbohydrates, the crystallization of API becomes completely suppressed. This is most likely due to additional barriers relating to the intermolecular interactions and diffusion of nifedipine that must be overcome to trigger the crystallization process.

A mutarotation mechanism based on dual proton exchange in the amorphous D-glucose.

It is a well known fact that carbohydrates have unusual chemical and physical properties when they approach the glassy state during the cooling process. Differences between sugar aqueous solutions and their pure anhydrous states are caused mainly by the different intermolecular interactions related to the different hydrogen bond patterns. The mutarotation, a specific reaction in the saccharides, was recently investigated in the supercooled liquid and the glassy state of D-glucose. It was shown that the activation energy of this process in the supercooled liquid state is twice as low as for the same process in aqueous solution. In contrast, the activation energy in the glassy state is twice as high as in the aqueous solution. Herein, we present possible explanations for this phenomenon and propose a universal mechanism for the mutarotation process in the amorphous state of matter. In this work, for the first time, a double proton exchange mechanism in carbohydrates is proposed.

Molecular dynamics of itraconazole at ambient and high pressure.

Comprehensive molecular dynamics studies of vitrified and cryogrounded itraconazole (Itr) were performed at ambient and elevated pressure. DSC measurements yielded besides melting and glass transition observed during heating and cooling of both samples two further endothermic events at around T = 363 K and T = 346 K. The nature of these transitions was investigated using X-ray diffraction, broadband dielectric spectroscopy and Density Functional Theory calculations. The X-ray measurements indicated that extra ordering in itraconazole is likely to occur. Based on calculations and theory derived by Letz et al. the transition observed at T = 363 K was discussed in the context of formation of the nematic mesophase. In fact, additional FTIR measurements revealed that order parameter variation in Itr shows a typical sequence of liquid crystal phases with axially symmetric orientational order; i.e. a nematic phase in the temperature range 361.7 K to 346.5 K and a smectic A phase below 346.5. Moreover, dielectric measurements demonstrated that except for the structural relaxation process, there is also slower mode above the glass transition temperature in both vitrified and cryogrounded samples. We considered the origin of this mode taking into account DFT calculations, rod like shape of itraconazole and distribution of its dipole moment vectors. For the dielectric data collected at elevated pressure, evolution of the steepness index versus pressure was determined. Finally, the pressure coefficient of the glass transition temperature was evaluated to be equal to 190 K GPa(-1).

Molecular dynamics of the supercooled pharmaceutical agent posaconazole studied via differential scanning calorimetry and dielectric and mechanical spectroscopies.

This paper presents comprehensive studies on the molecular dynamics of a pharmaceutically important substance, posaconazole. In order to characterize relaxation dynamics in the supercooled liquid and glassy states, dielectric and mechanical spectroscopies were applied. Dielectric data have indicated multiple relaxation processes that appear above and below the glass transition temperature Tg (τα=100 s) of posaconazole. From the curvature of the dielectric log10(τα) versus inverse of temperature dependence, we determine so-called "fragility", being a very popular parameter for classifying the structural dynamics of supercooled liquids and polymers. From the calculations, we get m=150, which means that is one of the most fragile glass-forming liquids. In this paper, the relaxation dynamics of supercooled posaconazole extracted from the dielectric response function was also confronted with shear-mechanical relaxation. Finally, we have also presented a direct comparison of the fragility and the number of dynamically correlated molecules Nc determined from dynamic calorimetry curves and dielectric and mechanical spectroscopies, showing a clear deviation in the picture of glass-transition dynamics generated by calorimetric and spectroscopic techniques.

Communication: Synperiplanar to antiperiplanar conformation changes as underlying the mechanism of Debye process in supercooled ibuprofen.

In this Communication, we present experimental studies that put new insight into the puzzling nature of the Debye relaxation found in the supercooled liquid state of racemic ibuprofen. The appearance of D-relaxation in the loss spectra of non-hydrogen bonding methylated derivate of ibuprofen has proven that Debye relaxation is related solely with conformational changes of the carboxyl group, termed in this paper as synperiplanar-antiperiplanar. Our studies indicate that the presence of hydrogen bonding capabilities is not here the necessary condition to observe Debye process, however, their occurrence might strongly influence α- and D-relaxations dynamics. Interestingly, the activation energy of the D-process in ibuprofen methyl ester on approaching T(g) was found to be perfectly consistent with that reported for ibuprofen by Affouard and Correia [J. Phys. Chem. B 114, 11397-11402 (2010)] (~39 kJ/mol). Finally, IR measurements suggest that the equilibrium between conformers concentration depends on time and temperature, which might explain why the appearance of D-relaxation in supercooled ibuprofen depends on thermal history of the sample.

Mutarotation in biologically important pure L-fucose and its enantiomer.

The sugar specific mutarotation reaction in biologically important L-fucose and its enantiomer in the pure, anhydrous, supercooled liquid state has been studied. Kinetics measurements in the temperature range 313-328 K at ambient pressure have been performed by means of dielectric spectroscopy, a method widely used for studying the molecular dynamics of glass-forming liquids. The kinetic curves have been obtained by tracking the equilibration process in sugar melted and quenched to the desired temperature. Thereafter, an activation energy equal to Ea = 140 kJ mol(-1) for D-fucose and Ea = 123 kJ mol(-1) for L-fucose has been derived from the Arrhenius fit of temperature dependent rate constants. It was also shown that the kinetics curves at the lowest temperatures studied have sigmoidal shape, which was connected to the high concentration of furanosidic forms.

Education of Sport University students regarding first-aid procedures after dental trauma.

AIM: The aim of this survey was to establish the current state of knowledge with regard to first-aid procedures and to compare the effectiveness of an educational lecture and a subsequent educational session. METHODS: A questionnaire to assess the attitudes and anticipated behaviours of Sport University students related to first-aid procedures following dental injury was administered to the students 3 times (after 3 and 12 months). A lecture on the subject of dental trauma was given just after the first questionnaire survey. A randomly selected students group received an extra educational task. RESULTS: The present study revealed a low level of initial knowledge of physical education students concerning first-aid measures in the case of dental trauma. A 30 minute lecture and an extra educational task significantly improved the knowledge evel. Even after one year the knowledge level was still high and sufficient to properly react when faced with dental trauma. CONCLUSION: Our research proves that the inclusion of dental trauma as a topic in the Sport University students' curricular training and paedagogical education should be introduced in the form of a clear and concise lecture.

A new way of stabilization of furosemide upon cryogenic grinding by using acylated saccharides matrices. The role of hydrogen bonds in decomposition mechanism.

Recently it was reported that upon mechanical milling of pure furosemide significant chemical degradation occurs (Adrjanowicz et al. Pharm. Res.2011, 28, 3220-3236). In this paper, we present a novel way of chemical stabilization amorphous furosemide against decomposing that occur during mechanical treatment by preparing binary mixtures with acylated saccharides. To get some insight into the mechanism of chemical degradation of furosemide induced by cryomilling, experimental investigations supported by density functional theory (DFT) computations were carried out. This included detailed studies on molecular dynamics and physical properties of cryoground samples. The main thrust of our paper is that we have shown that furosemide cryomilled with acylated saccharides forms chemically and physically stable homogeneous mixtures with only one glass transition temperature, Tg. Finally, solubility measurements have demonstrated that furosemide cryomilled with acylated saccharides (glucose, maltose and sucrose) is much more soluble with respect to the crystalline form of this active pharmaceutical ingredient (API).

Mechanism of mutarotation in supercooled liquid phase: Studies on L-sorbose.

We have studied mutarotation in anhydrous supercooled L-sorbose by means of dielectric spectroscopy. The phenomenon observed in L-sorbose is much faster than in the structurally similar D-fructose. The kinetics of this process has been determined by applying 1st order kinetics model. Activation energy equal to 68 kJ/mol was obtained from temperature dependence of rate constants. To understand differences in mutarotation rate between D-fructose and L-sorbose, quantum mechanical calculations were performed to study mechanism of this phenomenon. The possible impact of water absorbed from air on the mutarotation in supercooled liquid state has been checked. It turned out that the process is probably intermolecular and the water molecules or other carbohydrate molecules assist in the proton transfer process. Finally we have shown that the rate constant can be alternatively determined from frequency of the maximum of peak, obtained by performing Fourier transform of kinetic curve.

Role of hydrogen bonds and molecular structure in relaxation dynamics of pentiol isomers.

Although the presence of hydrogen bonds determines most properties of associated materials, their role in relaxation dynamics of liquids remains unclear. Very recently Nakanishi and Nozaki [M. Nakanishi and R. Nozaki, Phys. Rev. E 84, 011503 (2011)] proposed a simplified model for the description of the molecular dynamics of H-bonding network and tested its validity for several polyols. The authors concluded that relaxation dynamics is controlled mainly by the number of hydroxyl groups, whereas the role of molecular architecture can be neglected. This conclusion, as demonstrated herein, fails in the case of pentiols. When we take into account the role of molecular architecture for development of H-bonded structures, it is still possible to satisfactorily describe molecular dynamics in polyols with the use of the Nakanishi and Nozaki model.

Dielectric studies on molecular dynamics of two important disaccharides: sucrose and trehalose.

Broadband dielectric measurements were carried out in the supercooled as well as in the glassy state of two very important disaccharides: trehalose and sucrose. Multiple relaxation processes were observed. Above the glass transition temperatures of examined disaccharides structural relaxation of cooperative origin was detected, where in the glassy state more local motions (secondary modes) appeared. Our data were discussed in light of the findings reported by other groups. We pointed out that sample preparation might impact mobility and, thus, dielectric loss spectra in a significant way. Consequently, it may lead to misinterpretation of the dielectric relaxation processes. Moreover, impact of physical aging and pressure on dynamics of two secondary relaxation processes observed in the glassy state of trehalose and sucrose has been investigated. Additionally, we have demonstrated that, in contrast to the calorimetric measurements (DSC), activation energies of the ß- and γ-relaxation processes observed in the glassy state of sucrose and trehalose do not change as a result of physical aging. Finally, we found out that the ß-relaxation process slows down as pressure increases. We interpreted this fact in view of increasing rigidity of the structures of disaccharides.

Enhancement of amorphous celecoxib stability by mixing it with octaacetylmaltose: the molecular dynamics study.

In this paper, we present a novel way of stabilization of amorphous celecoxib (CEL) against recrystallization by preparing binary amorphous celecoxib-octaacetylmaltose (CEL-acMAL) systems by quench-cooling of the molten phase. As far as we know this is the first application of carbohydrate derivatives with acetate groups to enhance the stability of an amorphous drug. We found that CEL in the amorphous mixture with acMAL is characterized by a much better solubility than pure CEL. We report very promising results of the long-term measurements of stability of the CEL-acMAL binary amorphous system with small amount of stabilizer during its storage at room temperature. Moreover, we examined the effect of adding acMAL on molecular dynamics of CEL in the wide temperature range in both the supercooled liquid and glassy states. We found that the molecular mobility of the mixture of CEL with 10 wt % acMAL in the glassy state is much more limited than that in the case of pure CEL, which correlates with the better stability of the amorphous binary system. By dielectric measurements and theoretical calculations within the framework of density functional theory (DFT), we studied the role of acMAL in enhancing the stability of amorphous CEL in mixtures and postulated which interactions between CEL and acMAL molecules can be responsible for preventing devitrification.

The importance of the activation volume for the description of the molecular dynamics of glass-forming liquids.

High pressure dielectric measurements were carried out on hydrogen bonded d-glucose and two van der Waals peracetyl saccharides, i.e. α pentaacetyl glucose and α octaacetyl maltose. In this study we found that after removing H bonds, the molecular dynamics of both modified saccharides is very sensitive to pressure, as reflected by a large value of the pressure coefficient of the glass transition temperature, equal to 270 K GPa(-1) and 280 K GPa(-1) for α pentaacetyl glucose and α octaacetyl maltose, respectively. On the other hand, dT(g)/dP for d-glucose is much lower, equal to 67 K GPa(-1). Our result confirms the general rule that the hydrogen bonding glass-forming liquids exhibit much lower values of dT(g)/dP compared to the van der Waals systems. Additionally, on the basis of results reported herein and also recent literature data for polyalcohols, we point out that the activation volume correlates fairly well with the molecular volume in the case of hydrogen bonding liquids. On the other hand, much larger values of the activation volumes at T(g) with respect to the molecular volumes were found for both peracetyl saccharides.

Tracking of Proton Transfer Reaction in Supercooled RNA Nucleoside.

In this paper we address a longstanding debate concerning the proton transfer reaction of DNA and RNA compounds. The sample tested is ß-uridine, one of the four basic components of RNA, which has been suggested to have the capacity to adopt lactam and lactim tautomeric forms. The essential biological importance of this RNA nucleoside has motivated a number of experimental and theoretical investigations in the past. However, the kinetics of the proton transfer reaction of this compound has not been examined. Herein, we employ dielectric spectroscopy and refractive index measurements to experimentally characterize lactam-lactim transformation in the supercooled liquid state. We quantify the kinetics of ß-uridine tautomerization and suggest a mechanism for the configurational changes. The obtained data are compared to quantum chemical calculations. Finally the biological importance of our results is discussed.

Comment on "Study of dielectric relaxations of anhydrous trehalose and maltose glasses" [J. Chem. Phys. 134, 014508 (2011)].

Very recently Kwon et al. [H.-J. Kwon, J.-A. Seo, H. K. Kim, and Y. H. Hwang, J. Chem. Phys. 134, 014508 (2011)] published an article on the study of dielectric relaxation in trehalose and maltose glasses. They carried out broadband dielectric measurements at very wide range of temperatures covering supercooled liquid as well as glassy state of both saccharides. It is worth to mention that authors have also applied a new method for obtaining anhydrous glasses of trehalose and maltose that enables avoiding their caramelization. Four relaxation processes were identified in dielectric spectra of both saccharides. The slower one was identified as structural relaxation process the next one, not observed by the others, was assigned as Johari-Goldstein (JG) ß-relaxation, while the last two secondary modes were of the same nature as found by Kaminski et al. [K. Kaminski, E. Kaminska, P. Wlodarczyk, S. Pawlus, D. Kimla, A. Kasprzycka, M. Paluch, J. Ziolo, W. Szeja, and K. L. Ngai, J. Phys. Chem. B 112, 12816 (2008)]. In this comment we show that the authors mistakenly assigned the slowest relaxation process as structural mode of disaccharides. We have proven that this relaxation process is an effect of formation of thin layer of air or water between plate of capacitor and sample. The same effect can be observed if plates of capacitor are oxidized. Thus, we concluded that their slowest mode is connected to the dc conduction process while their ß JG process is primary relaxation of trehalose and maltose.

Theoretical and experimental studies on the internal mobility of two sulfonylurea agents: glibenclamide and glimepiride.

Molecular dynamics of glibenclamide and glimepiride in their glassy state were studied by means of broadband dielectric spectroscopy. In both compounds we found a γ-relaxation process, with nearly the same value of activation energy. Further, we were able to identify the origin of γ relaxation by performing calculations within the framework of density functional theory. It was found that rotation of the chain end included cyclohexyl and neighboring carbonyl group is related to the observed mode in dielectric spectra. The calculated activation energy was only a few kJ per mole lower than the energies obtained from experiment. It is demonstrated that this fast γ process is insensitive to pressure. Finally, another secondary mode in glibenclamide, predicted by computations, was confirmed from dielectric measurements at elevated pressure. Our calculations indicate that this mode should be pressure-sensitive.

Nanoscale domains with nematic order in supercooled vitamin-A acetate: molecular dynamics studies.

Vitamin-A acetate is one of the most versatile vitamins. It is applied in medicine because of its antioxidative properties, in tumor therapy because of its cytostatic activity, and in cosmetics because of its nutritional additives. Herein, using broadband dielectric spectroscopy, the molecular dynamics of supercooled and glassy vitamin-A acetate was investigated. It was shown that dielectric measurements carried out at ambient and elevated pressures reveal a number of relaxation processes associated with different types of molecular motions: α, δ, and ν processes-observed above the glass transition temperature and the next two modes: ß and γ identified in the glassy state. The occurrence of the δ mode in the dielectric spectrum may imply the existence of nanoscale domains with nematic order. This hypothesis is further checked by atomic force microscopy measurements. Finally, we have determined the value of the glass transition temperature (T(g)) as well as the steepness index (m(P)) at various T-P conditions.

Comparative dielectric studies on two hydrogen-bonded and van der Waals liquids.

Broadband dielectric measurements were performed in a wide range of temperatures on glucose, maltose, and their acetyl derivatives. We have indicated that molecular dynamics above and below the glass transition temperature differ considerably for the hydrogen-bonded and van der Waals systems. We have shown that structural relaxation dispersions of D-glucose and maltose are broader than those obtained for peracetyl carbohydrates. Moreover, glass transition temperatures of the former systems are much higher than for the latter ones. In the glassy state of both glucose and its acetyl derivatives only one well-separated secondary relaxation process was identified. In the case of maltose and peracetyl maltose a completely different situation was observed. In the former carbohydrate two secondary modes were detected, whereas in the latter one only a faster relaxation process was visible in the glassy state. This finding is discussed in greater detail on the basis of density functional theory calculations.