Search Results (40)

The particle size-dependent processes of structural relaxation and crystal growth in amorphous nifedipine were studied by means of non-isothermal differential scanning calorimetry (DSC) and Raman microscopy. The enthalpy relaxation was described in terms of the Tool–Narayanaswamy–Moynihan model, with the relaxation motions exhibiting the activation energy of 279 kJ·mol⁻¹ for the temperature shift, but with a significantly higher value of ~500 kJ·mol⁻¹ being obtained for the rapid transition from the glassy to the undercooled liquid state (the latter is in agreement with the activation energy of the viscous flow). This may suggest different types of relaxation kinetics manifesting during slow and rapid heating, with only a certain portion of the relaxation motions occurring that are dependent on the parameters of a given temperature range and time frame. The DSC-recorded crystallization was found to be complex, consisting of four sub-processes: primary crystal growth of α_p and β_p polymorphs, enantiotropic β_p → β_p′ transformation, and β_p/β_p′ → α_p recrystallization. Overall, nifedipine was found to be prone to the rapid glass-crystal growth that occurs below the glass transition temperature; a tendency of low-temperature degradation of the amorphous phase markedly increased with decreasing particle size (the main reason being the increased number of surface and bulk micro-cracks and mechanically induced defects). The activation energies of the DSC-monitored crystallization processes varied in the 100–125 kJ·mol⁻¹ range, which is in agreement with the microscopically measured activation energies of crystal growth. Considering the potential correlations between the structural relaxation and crystal growth processes interpreted within the Transition Zone Theory, a certain threshold in the complexity and magnitude of the cooperating regions (as determined from the structural relaxation) may exist, which can lead to a slow-down of the crystal growth if exceeded. Full article

The pH dependence of the free energy level of the flash-induced primary charge pair P⁺I_A⁻ was determined by a combination of the results from the indirect charge recombination of P⁺Q_A⁻ and from the delayed fluorescence of the excited dimer (P*) in the reaction center of the photosynthetic bacterium Rhodobacter sphaeroides, where the native ubiquinone at the primary quinone binding site Q_A was replaced by low-potential anthraquinone (AQ) derivatives. The following observations were made: (1) The free energy state of P⁺I_A⁻ was pH independent below pH 10 (–370 ± 10 meV relative to that of the excited dimer P*) and showed a remarkable decrease (about 20 meV/pH unit) above pH 10. A part of the dielectric relaxation of the P⁺I_A⁻ charge pair that is not insignificant (about 120 meV) should come from protonation-related changes. (2) The single exponential decay character of the kinetics proves that the protonated/unprotonated P⁺I_A⁻ and P⁺Q_A⁻ states are in equilibria and the rate constants of protonation k_on^H +k_off^H are much larger than those of the charge back reaction k_back ~10³ s⁻¹. (3) Highly similar pH profiles were measured to determine the free energy states of P⁺Q_A⁻ and P⁺I_A⁻, indicating that the same acidic cluster at around Q_B should respond to both anionic species. This was supported by model calculations based on anticooperative proton distribution in the cluster with key residues of GluL212, AspL213, AspM17, and GluH173, and the effect of the polarization of the aqueous phase on electrostatic interactions. The larger distance of I_A⁻ from the cluster (25.2 Å) compared to that of Q_A⁻ (14.5 Å) is compensated by a smaller effective dielectric constant (6.5 ± 0.5 and 10.0 ± 0.5, respectively). (4) The P* → P⁺Q_A⁻ and I_A⁻Q_A → I_AQ_A⁻ electron transfers are enthalpy-driven reactions with the exemption of very large (>60%) or negligible entropic contributions in cases of substitution by 2,3-dimethyl-AQ or 1-chloro-AQ, respectively. The possible structural consequences are discussed. Full article

Furins are serine endoproteases that are involved in many biological processes, where they play important roles in normal metabolism, in the activation of various pathogens, while they are a target for therapeutic intervention. Dichlorophenyl-pyridine “BOS” compounds are well known drugs that are used as inhibitors of human furin by an induced-fit mechanism, in which tryptophan W254 in the furin catalytic cleft acts as a molecular transition energy gate. The binding of “BOS” drug into the active center of furin has been computationally studied using the density functional theory (DFT) and ONIOM multiscaling methodologies. The binding enthalpies of the W254 with the furin-BOS is −32.8 kcal/mol (“open”) and −18.8 kcal/mol (“closed”), while the calculated torsion barrier was found at 30 kcal/mol. It is significantly smaller than the value of previous MD calculations due to the relaxation of the environment, i.e., nearby groups of the W254, leading to the reduction of the energy demands. The significant lower barrier explains the experimental finding that the dihedral barrier of W254 is overcome. Furthermore, sartans were studied to evaluate their potential as furin inhibitors. Sartans are AT1 antagonists, and they effectively inhibit the hypertensive effects induced by the peptide hormone Angiotensin II. Here, they have been docked into the cavity to evaluate their effect on the BOS ligand via docking and molecular dynamics simulations. A consistent binding of sartans within the cavity during the simulation was found, suggesting that they could act as furin inhibitors. Finally, sartans interact with the same amino acids as W254, leading to a competitive binding that may influence the pharmacological efficacy and potential drug interactions of sartans. Full article

Capitellacin is the β-hairpin membrane-active cationic antimicrobial peptide from the marine polychaeta Capitella teleta. Capitellacin exhibits antibacterial activity, including against drug-resistant strains. To gain insight into the mechanism of capitellacin action, we investigated the structure of the peptide in the membrane-mimicking environment of dodecylphosphocholine (DPC) micelles using high-resolution NMR spectroscopy. In DPC solution, two structural forms of capitellacin were observed: a monomeric β-hairpin was in equilibrium with a dimer formed by the antiparallel association of the N-terminal β-strands and stabilized by intermonomer hydrogen bonds and Van der Waals interactions. The thermodynamics of the enthalpy-driven dimerization process was studied by varying the temperature and molar ratios of the peptide to detergent. Cooling the peptide/detergent system promoted capitellacin dimerization. Paramagnetic relaxation enhancement induced by lipid-soluble 12-doxylstearate showed that monomeric and dimeric capitellacin interacted with the surface of the micelle and did not penetrate into the micelle interior, which is consistent with the “carpet” mode of membrane activity. An analysis of the known structures of β-hairpin AMP dimers showed that their dimerization in a membrane-like environment occurs through the association of polar or weakly hydrophobic surfaces. A comparative analysis of the physicochemical properties of β-hairpin AMPs revealed that dimer stability and hemolytic activity are positively correlated with surface hydrophobicity. An additional positive correlation was observed between hemolytic activity and AMP charge. The data obtained allowed for the provision of a more accurate description of the mechanism of the oligomerization of β-structural peptides in biological membranes. Full article

In an attempt to better understand the physics governing the apparition of reverse-light-induced excited spin state trapping (LIESST) phenomena in spin crossover (SCO) compounds, we have studied the LIESST effect and the possibility of a reverse-LIESST effect in the SCO complex Zn_1−xFex(6-mepy)₃tren(PF₆)₂·CH₃CN, x = 0.5%. ((6-mepy)₃tren = tris{4-[(6-methyl)-2-pyridyl]-3-aza-butenyl}amine)). This complex was chosen as a good candidate to show reverse-LIESST by comparison with its unsolvated analogue, since the introduction of acetonitrile in the structure leads to the stabilisation of the high-spin state and both exhibit a very abrupt thermal spin transition. Indeed, the steep thermal spin transitions of two differently polarised crystals of Zn_1−xFex(6-mepy)₃tren(PF₆)₂·CH₃CN, x = 0.5% have been characterised in detail in a first step using absorption spectroscopy and no influence of the polarisation was found. These were then fitted within the mean field model to obtain the variation in the enthalpy and entropy and the critical temperatures associated with the process, which are significantly lower with respect to the unsolvated compound due to the incorporation of acetonitrile. In a second step, the light-induced low-spin-to-high-spin transition at low temperatures based on LIESST and its subsequent high-spin-to-low-spin relaxation at different temperatures were characterised by time-resolved absorption spectroscopy, with exponential behaviour in both cases. The stabilisation of the high-spin state due to the presence of acetonitrile was evidenced. Finally, light-induced high-spin-to-low-spin state transition at low temperature based on reverse-LIESST was attempted by time-resolved absorption spectroscopy but the Fe(II) concentration was too low to observe the effect. Full article

The formation of the nematic to twist-bend nematic (N_TB) phase has emerged as a fascinating phenomenon in the field of supramolecular chemistry, based on complex intermolecular interactions. Through a careful analysis of molecular structures and dynamics, we elucidate how these intermolecular interactions drive the complex twist-bend modulation observed in the N_TB. The study employs broadband dielectric spectroscopy spanning frequencies from 10 to 2 × 10⁹ Hz to investigate the molecular orientational dynamics within the glass-forming thioether-linked cyanobiphenyl liquid crystal dimers, namely, CBSC7SCB and CBSC7OCB. The experimental findings align with theoretical expectations, revealing the presence of two distinct relaxation processes contributing to the dielectric permittivity of these dimers. The low-frequency relaxation mode is attributed to an “end-over-end rotation” of the dipolar groups parallel to the director. The high-frequency relaxation mode is associated with precessional motions of the dipolar groups about the director. Various models are employed to describe the temperature-dependent behavior of the relaxation times for both modes. Particularly, the critical-like description via the dynamic scaling model seems to give not only quite good numerical fittings, but also provides a consistent physical picture of the orientational dynamics in accordance with findings from infrared (IR) spectroscopy. Here, as the longitudinal correlations of dipoles intensify, the m₁ mode experiences a sudden upsurge in enthalpy, while the m₂ mode undergoes continuous changes, displaying critical mode coupling behavior. Interestingly, both types of molecular motion exhibit a strong cooperative interplay within the lower temperature range of the N_TB phase, evolving in tandem as the material’s temperature approaches the glass transition point. Consequently, both molecular motions converge to determine the glassy dynamics, characterized by a shared glass transition temperature, T_g. Full article

First-principle calculation analysis on electronic structures and molecular dynamics was performed to investigate the addition of gadolinium ion into a formamidinium lead iodine (FAPbI₃) perovskite crystal for use in the application of photovoltaic devices with stability of performance. Band dispersion, density of state, enthalpy, and kinetic energy were predicted during the relaxation process. The Gd²⁺-doped FAPbI₃ perovskite crystal had an effective mass ratio of 0.02 in narrow band dispersion, consisting of 5d and 4f orbitals of gadolinium ion, a 6p orbital of lead ion, and a 5p orbital of iodine ion, supporting the charge transfer and carrier diffusion related to carrier mobility as a photovoltaic parameter. The molecular dynamics of the Gd²⁺-doped perovskite crystal indicate dynamic stability while suppressing decomposition, with separation between nitrogen and hydrogen ions on FA in the crystal. The first-principle calculation predicts that it is advantageous to apply the Gd²⁺-doped FAPbI₃ perovskite crystal to the perovskite solar cell, providing stability of photovoltaic performance. Full article

The process of isothermal and non-isothermal physical ageing of amorphous polylactide (PLA) with the active pharmaceutical ingredient, indapamide (IND), was investigated. A PLA–IND system with a 50/50 weight ratio was obtained and characterized using differential scanning calorimetry (DSC). In the 50/50 (w/w) mixture, two glass transitions were observed: the first at 64.1 ± 0.3 °C corresponding to the glass transition temperature (T_g) of PLA, and the second at 102.6 ± 1.1 °C corresponding to the T_g of IND, indicating a lack of molecular mixing between the two ingredients. The PLA–IND system was subjected to the isothermal physical ageing process at different ageing temperatures (T_a) for 2 h. It was observed that the highest effect of physical ageing (enthalpy relaxation change) on IND in the PLA–IND system occurred at T_a = 85 °C. Furthermore, the system was annealed for various ageing times at 85 °C. The relaxation enthalpies were estimated for each experiment and fitted to the Kohlrausch–Williams–Watts (KWW) equation. The KWW equation allowed for the estimation of the relaxation time and the parameter describing the distribution of relaxation times of the isothermal physical ageing process of IND in the PLA–IND system. The physical ageing of the PLA–IND mixture (50/50) was also discussed in the context of heat capacity. Moreover, the activation energy and fragility parameters were determined for the PLA–IND (50/50) system. Full article

Calorimetric (from both isothermal micro-calorimetry and DSC), chiro-optical, viscometric and rheological data on aqueous solutions of pectic acid and low-methoxyl pectin (LMP), published over decades from different laboratories, have been comparatively revisited. The aim was to arrive at a consistent and detailed description of the behavior of galacturonan as a function of pH, i.e., of the degree of charging (as degree of dissociation, α) of the polyanion. The previously hypothesized pH-induced transition from a 3₁ to a 2₁ helix was definitely confirmed, but it has been shown, for the first time, that the transition is always coupled with loosening/tightening effects brought about by an increase in charge. The latter property has a twofold effect: the former effect is a purely physical one (polyelectrolytic), which is always a loosening one. However, in the very low range of pH and before the beginning of the transition, an increase in charge tightens the 3₁ helix by strengthening an intramolecular—but inter-residue—hydrogen bond. The value of the enthalpy change of 3₁ → 2₁ transition—+0.59 kcal·mol⁻¹—is bracketed by those provided by theoretical modeling, namely +0.3 and +0.8 kcal·mol⁻¹; the corresponding entropy value is also positive: +1.84 cal·mole r.u.⁻¹·K⁻¹. The enthalpic and the entropic changes in chain loosening amount only to about 23% of the corresponding 3₁ → 2₁ changes, respectively. Much like poly(galacturonic acid), the 3₁ conformation of LMP also stiffens on passing from pH = 2.5 to 3.0, to then start loosening and transforming into the 2₁ one on passing to pH = 4.0. Lowering the pH of a salt-free aqueous solution of LMP down to 1.6 brings about a substantial chain–chain association, which is at the root of the interchain junctions stabilizing the acid pH gels, in full agreement with the rheological results. A comparison of the enthalpic data reveals that, at 85 °C, LMP in acidic pH conditions has lost its initial order by about 2.3 times more than pectic acid brought from low charging to full neutralization (at α = 1.0) at 25 °C. A proper combination of experiments (enthalpic measurements) and theory (counterion condensation polyelectrolyte theory) succeeded in demonstrating, for the first time ever, a lyotropic/Hofmeister effect of the anion perchlorate in stabilizing the more disordered form of the 2₁ helix of galacturonan. The viscometric results in water showed that the 3₁ helix is capable of forming longer rheologically cooperative units compared with the 2₁ helix. Extrapolation to infinite ionic strength confirmed that, once all electrostatic interactions are cancelled, the elongation of the two helical forms is practically the same. At the same time, however, they indicated that the flexibility of the two-fold helix is more than fifteen times larger than that of the three-fold one. The result is nicely corroborated by a critical revisiting of ²³Na relaxation experiments. Full article

This paper studies the effects of annealing time on the specific heat enthalpy of polystyrene above the glass transition temperature. We extend the Tool–Narayanaswamy–Moynihan (TNM) model to describe the endothermic overshoot peaks through the dynamic mechanical spectra. In this work, we accept the viewpoint that the enthalpy recovery behavior of glassy polystyrene (PS) has a common structural relaxation mode with linear viscoelastic behavior. As a consequence, the retardation spectrum evaluated from the dynamic mechanical spectra around the primary T_g peak is used as the recovery function of the endothermic overshoot of specific heat. In addition, the sub-T_g shoulder peak around the T_g peak is found to be related to the structural relaxation estimated from light scattering measurements. The enthalpy recovery of annealed PS is quantitatively described using retardation spectra of the primary T_g, as well as the kinetic process of the sub-T_g relaxation process. Full article

In this work, film materials based on binary compositions of poly-(3-hydroxybutyrate) (PHB) and chitosan with different ratios of polymer components in the range from 0/100 to 100/0 wt. % were studied. Using a combination of thermal (DSC) and relaxation (EPR) measurements, the influence of the encapsulation temperature of the drug substance (DS) of dipyridamole (DPD) and moderately hot water (at 70 °C) on the characteristics of the PHB crystal structure and the diffusion rotational mobility of the stable TEMPO radical in the amorphous regions of the PHB/chitosan compositions is shown. The low-temperature extended maximum on the DSC endotherms made it possible to obtain additional information about the state of the chitosan hydrogen bond network. This allowed us to determine the enthalpies of thermal destruction of these bonds. In addition, it is shown that when PHB and chitosan are mixed, significant changes are observed in the degree of crystallinity of PHB, degree of destruction of hydrogen bonds in chitosan, segmental mobility, sorption capacity of the radical, and the activation energy of rotational diffusion in the amorphous regions of the PHB/chitosan composition. The characteristic point of polymer compositions was found to correspond to the ratio of the components of the mixture 50/50%, for which the inversion transition of PHB from dispersed material to dispersion medium is assumed. Encapsulation of DPD in the composition leads to higher crystallinity and to a decrease in the enthalpy of hydrogen bond breaking, and it also slows down segmental mobility. Exposure to an aqueous medium at 70 °C is also accompanied by sharp changes in the concentration of hydrogen bonds in chitosan, the degree of PHB crystallinity, and molecular dynamics. The conducted research made it possible for the first time to conduct a comprehensive analysis of the mechanism of action of a number of aggressive external factors (such as temperature, water, and the introduced additive in the form of a drug) on the structural and dynamic characteristics of the PHB/chitosan film material at the molecular level. These film materials have the potential to serve as a therapeutic system for controlled drug delivery. Full article

Water in a crosslinked dextran gel, Sephadex^® G25, is known to remain partially unfrozen during cooling and undergoes ice crystallization during rewarming. However, the mechanism of ice crystallization during rewarming is still unclear. To elucidate the frozen state of water in the gel, thermal behavior at low temperatures was investigated by using adiabatic calorimetry. Heat capacities and enthalpy-relaxation rates of the gel-containing water of mass ratio h (=g H₂O/g dry G25) = 1.00 were measured between 80 and 300 K during rewarming, where the gel was intermittently heated at the rate of 50–100 mK min⁻¹. Although an exotherm indicating ice crystallization during rewarming was confirmed with the gel precooled rapidly, at 5 K min⁻¹, it disappeared when precooled slowly, at 20 mK min⁻¹. During rewarming after the rapid cooling, two glass transitions were observed at ca. 175 K and 240–242 K. A higher-temperature glass transition due to the water trapped by the polymer network was not so clear, as it was overlapped with an endotherm due to the melting of small ice crystals, which indicates that the ice crystals formed have a broad size-distribution and that water in the gel is vitrified when ice crystals of even the smallest size cannot be formed. Full article

The polypeptide Nisin is characterized by antibacterial properties, making it a compound with many applications, mainly in the food industry. As a result, a deeper understanding of its behaviour, especially after its dissolution in water, is of the utmost importance. This could be possible through the study of aqueous solutions of Nisin by combining vibrational and acoustic spectroscopic techniques. The velocity and attenuation of ultrasonic waves propagating in aqueous solutions of the polypeptide Nisin were measured as a function of concentration and temperature. The computational investigation of the molecular docking between Nisin monomeric units revealed the formation of dimeric units. The main chemical changes occurring in Nisin structure in the aqueous environment were tracked using Raman spectroscopy, and special spectral markers were used to establish the underlying structural mechanism. Spectral changes evidenced the presence of the dimerization reaction between Nisin monomeric species. The UV/Vis absorption spectra were dominated by the presence of π → π* transitions in the peptide bonds attributed to secondary structural elements such as α-helix, β-sheets and random coils. The analysis of the acoustic spectra revealed that the processes primarily responsible for the observed chemical relaxations are probably the conformational change between possible conformers of Nisin and its self-aggregation mechanism, namely, the dimerization reaction. The activation enthalpy and the enthalpy difference between the two isomeric forms were estimated to be equal to ΔH₁* = 0.354 ± 0.028 kcal/mol and ΔH₁⁰ = 3.008 ± 0.367 kcal/mol, respectively. The corresponding thermodynamic parameters of the self-aggregation mechanism were found to be ΔH₂* = 0.261 ± 0.004 kcal/mol and ΔH₂⁰ = 3.340 ± 0.364 kcal/mol. The effect of frequency on the excess sound absorption of Nisin solutions enabled us to estimate the rate constants of the self-aggregation mechanism and evaluate the isentropic and isothermal volume changes associated with the relaxation processes occurring in this system. The results are discussed in relation to theoretical and experimental findings. Full article

PAF and related antifungal proteins are promising antimicrobial agents. They have highly stable folds around room temperature due to the presence of 3–4 disulfide bonds. However, unfolded states persist and contribute to the thermal equilibrium in aqueous solution, and low-populated states might influence their biological impact. To explore such equilibria during dimethyl sulfoxide (DMSO)-induced chemical unfolding, we studied PAF and its inactive variant PAF^D19S using nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC). According to the NMR monitoring at 310 K, the folded structures disappear above 80 v/v% DMSO concentration, while the unfolding is completely reversible. Evaluation of a few resolved peaks from viscosity-compensated ¹⁵N-¹H HSQC spectra of PAF yielded ∆G = 23 ± 7 kJ/M as the average value for NMR unfolding enthalpy. The NMR-based structures of PAF and the mutant in 50 v/v% DMSO/H₂O mixtures were more similar in the mixed solvents then they were in water. The ¹⁵N NMR relaxation dynamics in the same mixtures verified the rigid backbones of the NMR-visible fractions of the proteins; still, enhanced dynamics around the termini and some loops were observed. DSC monitoring of the T_m melting point showed parabolic dependence on the DMSO molar fraction and suggested that PAF is more stable than the inactive PAF^D19S. The DSC experiments were irreversible due to the applied broad temperature range, but still suggestive of the endothermic unfolding of PAF. Full article

Convection melting in metal foam under sinusoidal temperature boundary conditions is numerically studied in the present study. A multiple-relaxation-time lattice Boltzmann method, in conjunction with the enthalpy approach, is constructed to model the melting process without iteration steps. The effects of the porosity, phase deviation, and periodicity parameter on the heat-transfer characteristics are investigated. For the cases considered in this work, it is found that the effects of the phase deviation and periodicity parameter on the melting rate are weak, but the melting front can be significantly affected by the sinusoidal temperature boundary conditions. Full article