Calorimetric Investigation Research Articles

Crystallographic, kinetic, and calorimetric investigation of PKA interactions with L-type calcium channels and Rad GTPase

β-adrenergic signalling activates cAMP-dependent protein kinase (PKA), which regulates the activity of L-type voltage-gated calcium channels such as CaV1.2. Several PKA target sites in the C-terminal tail of CaV1.2 have been identified, and their phosphorylation has been suggested to increase currents in specific tissues or heterologous expression systems. However, augmentation of CaV1.2 currents in the heart is instead mediated by phosphorylation of Rad, a small GTPase that can inhibit CaV1.2. It is unclear how each of the proposed target sites in CaV1.2 and Rad rank towards their recognition by PKA, which could reveal a preferential phosphorylation. Here we used quantitative assays on three CaV1.2 and four Rad sites. Isothermal titration calorimetry (ITC) and enzyme kinetics show that there are two Tiers of targets, with CaV1.2 residue Ser1981 and Rad residues Ser25 and Ser272 forming Tier 1 substrates for PKA. These share a common feature with two Arginine residues at specific positions that can anchor the peptide into the substrate binding cleft of PKA. In contrast, PKA shows minimal activity for the other, Tier 2 substrates, characterized by low kcat values and undetectable binding via ITC. The existence of two Tiers suggests that PKA regulation of the CaV1.2 complex may occur in a graded fashion. We report crystal structures of the PKA catalytic subunit with and without a CaV1.2 and test the importance of several anchoring residues via mutagenesis. Different target sites utilize different anchors, highlighting the plasticity of PKAc to recognize substrates.

Exploring the interaction of hesperetin-mediated green synthesised gold and silver nanoparticles with human serum albumin: A comparative analysis

This study focused on evaluating the potential of hesperetin-functionalized silver (H-AgNPs) and gold nanoparticles (H-AuNPs) for biomedical use, with a primary objective of understanding their relative binding affinity to human serum albumin (HSA). We evaluated the strength and possible binding mechanisms of the interaction between the nanoparticles and HSA based on analyses from fluorescence studies, UV–visible absorption, lifetime measurements and isothermal titration calorimetry (ITC). Circular dichroism analysis was employed to examine the conformational changes in HSA upon complexation with H-AgNPs and H-AuNPs. Furthermore, the thermodynamic parameters derived from ITC provided insights into the stabilising forces driving the endothermic binding processes. Consistently, the binding constants derived from spectroscopic and calorimetric investigations elucidated the superior binding efficiency of H-AuNPs compared to H-AgNPs with HSA. Antibacterial study revealed that H-AgNPs exhibited significant activity against S. aureus and E. coli, revealing promising antibacterial effects. Contrarily, H-AuNPs demonstrated no activity in the study. From the MTT assay results, we observed that H-AgNPs exhibited higher anticancer activity against human lung cancer cells compared to H-AuNPs, while H-AuNPs demonstrated lower cytotoxicity than H-AgNPs. Based on our research findings, both nanoparticles hold promise as potential candidates for diverse applications in the therapeutic field.

A calorimetric and Raman spectroscopy study on the phase behavior of DIOX + CO2 hydrate

This work presents a calorimetric and Raman spectroscopy investigation on the phase behavior of DIOX (1,3-Dioxolane) + CO2 hydrate. A high-pressure micro-differential scanning calorimeter (HP μ-DSC) was used to determine the phase equilibrium data of DIOX + CO2 hydrate formed at 1 mol% and 5.56 mol% DIOX. A high-pressure in situ Raman spectroscopy apparatus was used to record the transient CO2 Raman spectra. The spectra were employed to study CO2 incorporation into the hydrate cages during the DIOX hydrate formation process. The results indicate that the DIOX + CO2 hydrate formed at 5.56 mol% DIOX is more stable than that formed at 1 mol% DIOX. The amount of DIOX + CO2 hydrate is increased when increasing the pressure from 3.0 MPa to 4.8 MPa, and more CO2 molecules are captured in the hydrate. Through the in situ Raman spectroscopy experiments, it is found that DIOX hydrate formed quickly at the beginning of the experiment and CO2 molecules were trapped in the small cages more slowly than the incorporation of DIOX into the hydrate. The results reported in this work have confirmed the feasibility of using DIOX as a thermodynamic additive to promote the hydrate-based CO2 capture.

Calorimetric Investigation of Magnetic Transitions in GdPdAl and TbPdAl

Calorimetric Investigation of Magnetic Transitions in GdPdAl and TbPdAl

Host-Guest Complexes of Flavanone and 4'-Chloroflavanone with Naturals and Modified Cyclodextrin: A Calorimetric and Spectroscopy Investigations.

The aim of the research was to investigate and compare the interaction between flavanones (flavanone, 4-chloro-flavanone) with potential anticancer activity and selected cyclodextrins. Measurements were made using calorimetric (ITC, DSC) and spectrophotometric (UV-Vis spectroscopy, FT-IR, 1H NMR) methods. The increase in the solubility in aqueous medium caused by the complexation process was determined by the Higuchi-Connors method. As a result of the study, the stoichiometry and thermodynamics of the complexation reaction were determined. The formation of stable inclusion complexes at a 1:1 M ratio between flavanone and 4-chloroflavanone and the cyclodextrins selected for research was also confirmed.

Calorimetric investigation on heat release during the disintegration process of pharmaceutical tablets

The compendial USP〈701〉 disintegration test method offers a crucial pass/fail assessment for immediate release tablet disintegration. However, its single end-point approach provides limited insight into underlying mechanisms. This study introduces a novel calorimetric approach, aimed at providing comprehensive process profiles beyond binary outcomes. We developed a novel disintegration reaction calorimeter to monitor the heat release throughout the disintegration process and successfully obtained enthalpy change profiles of placebo tablets with various porosities. The formulation comprised microcrystalline cellulose (MCC), anhydrous lactose, croscarmellose sodium (CCS), and magnesium stearate (MgSt). An abrupt temperature rise was observed after introducing the disintegration medium to tablets, and the relationship between the heat rise time and the tablet’s porosity was investigated. The calorimeter’s sensitivity was sufficient to discern distinct heat changes among individual tablets, and the analysis revealed a direct correlation between the two. Higher porosity corresponded to shorter heat rise time, indicating faster disintegration rates. Additionally, the analysis identified a concurrent endothermic process alongside the anticipated exothermic phenomenon, potentially associated with the dissolution of anhydrous lactose. Since lactose is the only soluble excipient within the blend composition, the endothermic process can be attributed to the absorption of heat as lactose molecules dissolve in water. The findings from this study underscore the potential of utilising calorimetric methods to quantify the wettability of complex compounds and, ultimately, optimise tablet formulations.

Thermal and calorimetric investigations of some vegetative fuels

AbstractBushfires pose a significant threat to numerous countries, often causing vast property damages and loss of lives. Efforts to combat and manage these fires heavily rely on predicting the fires' rate of spread and intensity. A significant component of these predictions involves understanding the thermophysical characteristics of vegetative fuels. The accuracy of predictive models (especially physical models) also depends on obtaining precise thermophysical and combustion parameters. This research aims to provide a comprehensive set of thermal degradation and combustion parameters for surface and near‐surface fuel samples collected during prescribed fire experiment conducted in April 2022 in Little Desert National Park, Victoria, Australia. Firstly, fuel properties like fuel height, moisture content, bulk density, fuel load and heat of combustion were meticulously characterized for both surface and near‐surface samples. Then activation energies for degradation reactions were determined using the Flynn–Wall–Ozawa method and for the determination of pre‐exponential factors, in most cases these reactions closely aligned with a Second order model. This was followed by determination of other parameters such as heat of reaction, specific heat and conductivity. It was found that the density, activation energy and heat of combustion did not vary significantly across the six samples under question. The comprehensive set of obtained parameters will likely help to facilitate better predictions in fire propagation modelling.

Calorimetric Studies and Thermodynamic Modeling of Ag-Mg-Ti Liquid Alloys.

Due to the absence of thermodynamic data concerning the Ag-Mg-Ti system in the existing literature, this study aims to fill this gap by offering the outcomes of calorimetric investigations conducted on ternary liquid solutions of these alloys. The measurements were performed using the drop calorimetry method at temperatures of 1294 K and 1297 K for the liquid solutions with the following constant mole fraction ratio: xAg/xMg = 9/1, 7/3, 1/1, 3/7 [(Ag0.9Mg0.1)1-xTix, (Ag0.7Mg0.3)1-xTix, (Ag0.5Mg0.5)1-xTix, (Ag0.3Mg0.7)1-xTix)], and xAg/xTi = 19/1 [(Ag0.95Ti0.05)1-xMgx]. The results show that the mixing enthalpy change is characterized by negative deviations from the ideal solutions and the observed minimal value equals -13.444 kJ/mol for the Ag0.95Ti0.05 alloy and xMg = 0.4182. Next, based on the thermodynamic properties of binary systems described by the Redlich-Kister model and the determined experimental data from the calorimetric measurements, the ternary optimized parameters for the Ag-Mg-Ti liquid phase were calculated by the Muggianu model. Homemade software (TerGexHm 1.0) was used to optimize the calorimetric data using the least squares method. Next, the partial and molar thermodynamic functions were calculated and are presented in the tables and figures. Moreover, this work presents, for comparative purposes, the values of the enthalpy of mixing of liquid Ag-Mg-Ti alloys, which were calculated using Toop's model. It was found that the best agreement between the modeled and experimental data was observed for the cross-sections xAg/xTi = 19/1 [(Ag0.95Ti0.05)1-xMgx] and xAg/xMg = 9/1 [(Ag0.9Mg0.1)1-xTix]. The results of the experiments presented in this paper are the first step in the investigation and future evaluation of the thermodynamics of phases and the calculation of the phase diagram of the silver-magnesium-titanium system.

Differential scanning calorimetric investigations of binaries formed between thermotropic liquid crystals

Differential scanning calorimetric investigations of binaries formed between thermotropic liquid crystals

Phase transitions of choline dihydrogen phosphate: A vibrational spectroscopy and periodic DFT study.

Choline dihydrogen phosphate, [Chol][H2PO4], is a proton-conducting ionic plastic crystal exhibiting a complicated sequence of phase transitions. Here, we address the argument in the literature around the thermal properties of [Chol][H2PO4] using Raman and infrared microspectroscopy. The known structure of the low-temperature crystal, which contains the anti-conformer of [Chol]+ and hydrogen-bonded dimers of anions, was used to do periodic density functional theory calculations of the vibrational frequencies. Raman spectra indicate that the solid-solid transition at 20 °C is linked to a conformational change to the gauche [Chol] conformer with a concurrent local rearrangement of the anions. The distinct bands of lattice modes in the low-frequency range of the Raman spectra vanish at the 20 °C transition. Given the ease with which metastable crystals can be produced, Raman mappings demonstrate that a sample of [Chol][H2PO4] at ambient temperature can contain a combination of anti- and gauche conformers. Heating to 120 °C causes continuous changes in the local environment of anions rather than melting as suggested by a recent calorimetric investigation of [Chol][H2PO4]. The monotonic change in vibrational spectra is consistent with earlier observations of a very small entropy of fusion and no abrupt jump in the temperature dependence of ionic conductivity along the phase transitions of [Chol][H2PO4].

Time resolved calorimetric investigations of photoinduced isomeric molecular changes in the nematic phase of an azobenzene compound

By monitoring the time dependence of the thermal conductivity of a p,p’-diheptylazobenzene sample irradiated with UV light of various intensities, a quantitative study is presented on the effects played by the photo-induced trans to cis isomerization on the degree of the homeotropic alignment in its nematic phase. In particular, the kinetics of the changes eventually leading to the nematic–isotropic phase transformation has been investigated. Unlike the case of the thermal diffusivity analyzed in a recent study, the thermal conductivity analysis has enabled the quantitative evaluation of the trans–cis transformation rates since it is not affected by the specific heat critical behavior and, therefore, it is determined only by changes in the molecular structure induced by the photo-isomerization. The study has been possible thanks to the peculiarity of the adopted photopyroelectric calorimetric setup that enabled both the calorimetric evaluations, as well as the sample texture characterization, to be performed during the UV illumination of the sample.

Interaction of food colorant indigo carmine with human and bovine serum albumins: A multispectroscopic, calorimetric, and theoretical investigation

In this work we have studied the interaction of the food dye Indigo-Carmine (IndC) with the most studied model transport proteins i.e. human and bovine serum albumin (HSA & BSA). A multispectroscopic approach was used to analyze the details of the binding process. The intrinsic fluorescence of both the albumins was significantly quenched by IndC and the quenching was both static and dynamic in nature with the former being dominant. The HSA-lndC and BSA-IndC distance after complexation was determined by Förster resonance energy transfer (FRET) method which suggested efficient energy transfer from the albumins to IndC. Thermodynamics of serum protein-IndC complexation was estimated by isothermal titration calorimetry (ITC) which revealed that the binding was enthalpy driven. Circular dichroism (CD) and FTIR spectroscopy revealed that the binding of IndC induced secondary structural changes in both the serum proteins. Synchronous and 3D fluorescence spectroscopy revealed that the binding interaction caused microenvironmental changes of protein fluorophores. Molecular docking analysis suggested that hydrogen bonding and hydrophobic interactions are the major forces involved in the complexation process.

Thermodynamic study on hydrated bilayers of ether-linked phosphatidylcholines with terminal perfluorobutyl group

Novel terminally perfluorobutyl group-containing ether-linked phosphatidylcholines with different alkyl chain lengths (di-O-F4-Cn-PCs, n = 14,16 and 18) were developed as possible materials for stable liposomes aiming at applications of structural and functional analyses of membrane proteins. Differential scanning calorimetric investigations of the thermotropic transition of hydrated di-O-F4-Cn-PC bilayers demonstrated that the transition temperature of every di-O-F4-Cn-PC decreases by ~20 °C compared to their corresponding non-fluorinated PCs, di-O-Cn-PCs. With the elongation of the hydrophobic chain, on the other hand, the transition enthalpy (ΔH) and entropy (ΔS) increased in a linear manner. Comparison of ΔH and ΔS values against the net hydrocarbon chain length between di-O-F4-Cn-PCs and di-O-Cn-PCs strongly suggests that in the thermotropic transition of the di-O-F4-Cn-PC membrane, the perfluorobutyl segments undergo very limited structural changes; therefore, the hydrocarbon segments are mainly responsible for the phase transition.

Mesoporous Matrices as a Promising New Generation of Carriers for Multipolymorphic Active Pharmaceutical Ingredient Aripiprazole.

The enhancement of the properties (i.e., poor solubility and low bioavailability) of currently available active pharmaceutical ingredients (APIs) is one of the major goals of modern pharmaceutical sciences. Among different strategies, a novel and innovative route to reach this milestone seems to be the application of nanotechnology, especially the incorporation of APIs into porous membranes composed of pores of nanometric size and made of nontoxic materials. Therefore, in this work, taking the antipsychotic API aripiprazole (APZ) infiltrated into various types of mesoporous matrices (anodic aluminum oxide, native, and silanized silica) characterized by similar pore diameters (d = 8-10 nm) as an example, we showed the advantage of incorporated systems in comparison to the bulk substance considering the crystallization kinetics, molecular dynamics, and physical stability. Calorimetric investigations supported by the temperature-dependent X-ray diffraction measurements revealed that in the bulk system the recrystallization of polymorph III, which next is converted to the mixture of forms IV and I, is visible, while in the case of confined samples polymorphic forms I and III of APZ are produced upon heating of the molten API with different rates. Importantly, the two-step crystallization observed in thermograms obtained for the API infiltrated into native silica templates may suggest crystal formation by the interfacial and core molecules. Furthermore, dielectric studies enabled us to conclude that there is no trace of crystallization of spatially restricted API during one month of storage at T = 298 K. Finally, we found that in contrast to the crystalline and amorphous bulk samples, all examined confined systems show a logarithmic increase in API dissolution over time (very close to a prolonged release effect) without any sign of precipitation. Our data demonstrated that mesoporous matrices appear to be interesting candidates as carriers for unstable amorphous APIs, like APZ. In addition to protecting them against crystallization, they can provide the desired prolonged release effect, which may increase the drug concentration in the blood (resulting in higher bioavailability). We believe that the "nanostructirization" in terms of the application of porous membranes as a novel generation of drug carriers might open unique perspectives in the further development of drugs characterized by prolonged release.

Probing the interaction and aggregation of lysozyme in presence of organophosphate pesticides: a comprehensive spectroscopic, calorimetric, and in-silico investigation

Organophosphorus pesticides (OPs) are widely used in agriculture and may contaminate food or water, leading to potential health risks. However, there are few reports on the effect of OPs on protein conformation and aggregation. Hence, in this paper, we have characterized the impact of two OPs, chlorpyrifos (CPF) and methyl parathion (Para), on the model protein HEWL using biophysical and computational methods. The steady-state and time-resolved spectroscopy, Circular dichroism (CD), molecular dynamics simulation, and isothermal titration calorimetry were employed to investigate the binding interactions between HEWL and OPs. The steady-state and time-resolved fluorescence spectroscopy confirm the presence of both static and dynamic quenching between OPs and proteins. Based on fluorescence, MD, and CD results, it was found that the OPs not only show strong binding but also destabilize the protein structure and alter the secondary and tertiary structure of the protein. The molecular docking results showed that OPs entered the binding pocket of the HEWL molecule and interacted through hydrophobic and hydrogen bond interactions. The thermodynamic studies indicated that the binding was spontaneous and OPs have shown an effect on the aggregation process of HEWL. Finally, the protein aggregation process was studied using fluorescence and SDS-PAGE studies in the presence of both the OPs and found to enhance the aggregation process in the presence of OPs. These results provide insights into the potential health risks associated with OPs and highlight the importance of understanding their interactions with biological macromolecules. Communicated by Ramaswamy H. Sarma

Optimization and Production of Aceclofenac-Loaded Microfiber Solid Dispersion by Centrifugal Spinning.

Aceclofenac-loaded polyvinylpyrrolidone fiber-based amorphous solid dispersion was produced successfully by centrifugal spinning. The solution concentration and rotational speed were optimized to produce the fiber-based drug carrier system, with a determined production rate of 12.7 g/h dry solid fibers. The obtained fibers were bead-free and smooth-surfaced with an average diameter of 7.5 ± 2.5 μm. Gas chromatographic determinations revealed that ethanol, as a residual solvent, was well below the regulatory limit of 0.5%. Differential scanning calorimetric investigation and infrared spectroscopic measurements were used to track the physicochemical changes that intervene during fiber formation in the solid state. The results revealed that the rapid evaporation of the solvent was accompanied by a probable crystalline to amorphous transition of the active substance during centrifugal spinning. In vitro dissolution studies revealed an instantaneous disintegration of the fibrous structure and a rapid release of the active substance, with the microfibrous webs greatly outperforming the crystalline active substance, especially in the early time-points. This implies that centrifugal spinning offers a viable scale-up production process to prepare drug-loaded fiber-based solid dispersions.

Response to the comments made by Vytenis Babrauskas on “the curious case of the second/end peak in the heat release rate of wood: A cone calorimeter investigation”

Response to the comments made by Vytenis Babrauskas on “the curious case of the second/end peak in the heat release rate of wood: A cone calorimeter investigation”

Non-Contact and Self-Calibrated Photopyroelectric Method for Complete Thermal Characterization of Porous Materials.

A general theory of a photopyroelectric (PPE) configuration, based on an opaque sample and transparent pyroelectric sensor, backing and coupling fluids is developed. A combined back-front detection investigation, based on a frequency scan of the phase of the PPE signals, followed by a self-normalization of the phases' behavior, leads to the possibility of simultaneously measuring both thermal effusivity and diffusivity of a solid sample. A particular case of this configuration, with no coupling fluid at the sample/backing interface and air instead of coupling fluid at the sample/sensor interface (non-contact method) is suitable for simultaneous measurement ofboth thermal diffusivity and effusivity (in fact complete thermal characterization) of porous solids. Compared with the already proposed configurations for investigations of porous materials, this novel configuration makes use of a fitting procedure with only one fitting parameter, in order to guarantee the uniqueness of the solution. The porous solids belong to a class of materials which are by far not easy to be investigated using PPE. To the best of our knowledge, porous materials represent the only type of compounds, belonging to condensed matter, which were not taken into consideration (until recently) as potential samples for PPE calorimetric investigations. Consequently, the method proposed in this paper complete the area of applications of the PPE method. Applications on some porous building materials and cellulose-based samples validate the theory.

Structural origin of room-temperature ferroelectricity in spark-plasma sintered DyCrO3 and LaCrO3

Identification of novel multiferroic materials with high-ordering temperatures remains at the forefront of condensed matter physics research. Recently, room-temperature ferroelectricity of structural origin, arising from off-centering displacements of Gd and Cr ions, has been identified in spark-plasma sintered (SPS) ${\mathrm{GdCrO}}_{3}$ [Suryakanta Mishra et al., Phys. Rev. B 104, L180101 (2021)]. Here, using a similar synthesis protocol (involving SPS), we have been able to engineer room-temperature ferroelectricity (FE) from a similar mechanism in two otherwise nonferroelectric $\mathit{R}{\mathrm{CrO}}_{3}$ (R= rare-earth) compounds, namely, ${\mathrm{DyCrO}}_{3}$ (which is reported as a quantum paraelectric) and ${\mathrm{LaCrO}}_{3}$ (which is already known to be paraelectric). Room-temperature FE in SPS-${\mathrm{LaCrO}}_{3}$ and SPS-${\mathrm{DyCrO}}_{3}$ is confirmed through various electrical, calorimetric, and synchrotron-based structural investigations. Out of these two emergent room-temperature FE materials, SPS-${\mathrm{LaCrO}}_{3}$ also undergoes a high-temperature antiferromagnetic ordering at 290 K, thus coming very close to becoming the first room-temperature multiferroic material in this promising family of $\mathit{R}{\mathrm{CrO}}_{3}$ compounds.

Comments on “The curious case of the second/end peak in the heat release rate of wood: A cone calorimeter investigation,” by Sanned et al.

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