Negative Enthalpy Research Articles

Solubility modelling and thermodynamic properties of allopurinol in aqueous solutions of four deep eutectic solvents

The aqueous solubilities of allopurinol in some choline chloride (ChCl) based deep eutectic solvents (DESs) with urea, glycerol, citric acid and glycol as neoteric green solvents were measured by the shake-flask method at T = (293.15–333.15) K under atmospheric pressure p = 101.1 kPa. The solubility in these solvents increased more than approximately 27.8-fold for ChCl/urea system, 45.6-fold for ChCl/glycerol system, 31-fold for ChCl/glycol system and 56-fold for ChCl/citric acid system with increasing the weight fraction of DESs. The solubility data was accurately correlated by the λh equation and modified Apelblat equation. The largest percentage of relative average deviation was 1.49 × 10−2, and the maximum value of root-mean-square deviation was 2.43 × 10−5. Also, in order to describe the thermodynamic behaviour of allopurinol in the aqueous DESs solutions, the transfer properties were derived. The negative Gibbs free energy (ΔtrGo) and enthalpy (ΔtrHo) values indicated that the transfer of allopurinol from neat water to aqueous DESs solutions was spontaneous and energetically favourable. Additionally, the ΔtrGo and ΔtrHo values decreased with the increase in the DESs concentrations, indicating that solubilization was more favourable with the increase in the DESs concentrations. In particular, the ΔtrGo values considerably decreased for ChCl/citric acid compared to ChCl/urea, ChCl/glycerol and ChCl/glycol mixtures. ChCl/citric acid is an effective additive for improving the solubility of allopurinol. Furthermore, the excess enthalpy of solution was obtained according to the λh equation.

Novel BTK inhibitor acalabrutinib (ACP-196) tightly binds to site I of the human serum albumin as observed by spectroscopic and computational studies.

Spectrofluorometric, UV-vis spectroscopic and theoretical tools were recruited to comprehend the interaction of acalabrutinib (ACP-196; ACLB) with human serum albumin (HSA). Fluorescence intensity determinations revealed that ACLB statically quenched the HSA-native fluorescence. Analysis of the observed fluorescence data resulting from the ACLB-HSA interaction presented binding constants in the range of 6.65-7.54 × 104 M-1 with the studied temperatures. Those constants showed steady decline with the rising temperatures that further signifies static interaction of the HSA and ACLB. Binding energetics were also interpreted using the fluorescence-recorded results that exhibited a spontaneous exothermic binding reaction with a negative change in Gibbs free energy as well as negative enthalpy and positive entropy changes. Those results suggested the involvement of electrostatic forces as discovered by further computational investigation. Those docking results verified that ACLB binds to domain IIA (site I) of the HSA as demonstrated experimentally by site markers displacement binding studies. Circular dichroism studies along with the synchronous and 3D fluorescence observations showed that ACL binding does not alter the HSA conformation.

Dynamic and structural heterogeneity in undercooled miscible and immiscible metallic liquid

Molecular dynamics computer simulations are performed to study the structure and dynamic relaxation of the metallic alloys Cu50Ag50 and Cu50Zr50 with and without miscibility gap, respectively. The interactions between the particles are modeled by an effective potential of the modified embedded atom method (MEAM). Cu50Zr50 undercooled liquid shows negative mixing enthalpy; the stronger interaction of heterogeneous atom pairs than that of homogeneous atom pairs, the longer the α-relaxation time and the lower the diffusion coefficient than that of the Cu50Ag50 liquid. Dynamic relaxation is related to the structural heterogeneity: the amount of five-fold symmetry (icosahedron-like) clusters is predominant in Cu50Zr50 melts, which hinders the movement of atoms and increases the dynamic relaxation time. The amount of non-five-fold symmetry (crystal-like) clusters is more pronounced in Cu50Ag50 melts, which leads to shorter dynamic relaxation time and enhanced crystallization of the Cu50Ag50 melt. The quantitative relationship between the five-fold symmetry parameter W and the diffusion coefficient D, as well as the α-relaxation time τα, is obtained in the two distinct undercooled liquids. The present work provides an understanding of the atomic-scale structure and the dynamic properties in the miscible and immiscible liquid mixtures.

Nanoencapsulation as fluorescence enhancer of vitamin L1 (anthranilic acid). An exhaustive study

This paper describes the guest-host complex formation of anthranilic acid (2-aminobenzoic acid, AA) and different natural and modified cyclodextrins (CDs), using steady state fluorescence. The experimental data point to the formation of 1:1 inclusion complexes with natural (ß and ɣ-CD) and modified (HP-ß, HE-ß and M-ß-CD) CDs. Of the natural CDs, the ß-CD complex showed the highest encapsulation constant (KF) value (14056 ± 1241 M−1). However, modified ß-CDs showed higher binding constants than ß-CDs. Of the modified CDs, M-β-CD showed the highest KF (18622 ± 897 M−1). To gain information on the encapsulation process of M-ß-CD/AA, the thermodynamic parameters of the complexation (ΔH, ΔS and ΔG), were studied. The results showed positive entropy (66 ± 7.9 J mol−1 K−1), negative enthalpy (−5.74 ± 2.96 kJ mol−1) and a change in Gibbs free energy at 25 °C (−24.30 ± 0.27 kJ mol−1). Finally, a computational study carried out using molecular docking simulations showed the high correlation between experimental values and computed scores. The complexation of M-ß-CD/AA depends on several physicochemical factors including temperature and pH. The values of KF exhibited a strong negative relation with temperature and pH. Moreover, the interaction of AA and M-ß-CD was most effective in the pH region where the molecule presents intramolecular hydrogen bonds that neutralize the charge of the protonated species of AA.

Thermodynamics of adsorption on nanocellulose surfaces

Understanding the thermodynamic interactions of cellulose nanomaterials with their environment is important to understand the forces behind their self-organization and co-organisation with other compounds, and to be able to use self-assembly to form new functional multicomponent materials. This review analyzes published studies that determined the thermodynamic parameters of the surface interactions of and adsorption of various compounds (proteins, polymers, and small molecules/ions) onto cellulose nanomaterials. We compiled the data reported and performed a meta-analysis for better comparison and to find trends in the published data. We first introduce the methods employed and describe the adsorption isotherm models typically used to describe the adsorption thermodynamics on nanocellulose surfaces. We then discuss and analyze the published results for the interaction of the various compounds with nanocellulose surfaces. The systems that have been reported on most were adsorption of natural binding proteins and various pollutants from water, such as heavy metal ions, dyes, and drugs. Interactions between cellulose surfaces and the cellulose binding module were generally both enthalpy- and entropy-driven, where the negative binding enthalpy indicates the formation of specific interactions between peptides and the carbohydrate backbone. On the other hand, interactions with charged molecules were mostly endothermic and purely entropy-driven, indicating that the adsorption on nanocellulose surfaces can be described as an interaction between opposite charges, where the entropy increase that arises from the release of surface-structured water molecules and counterions from the electronic double layer supplies the major contribution to the free energy of adsorption. We performed a meta-analysis on all published data, and found a linear relationship between ∆H and ∆S with the slope equal to the reference temperature, irrespective of whether the interacting compound is a specific cellulose binding protein, a non-specific binding protein, a polymer, or a small molecule/ion. This indicates that the process of adsorption is the same for all compounds and takes place with a constant change in Gibbs free energy of interaction, ∆G, where a change in interaction enthalpy is offset by change in entropy change upon binding and vice versa.

Enhanced formation and improved thermal stability of ferromagnetic τ phase in nanocrystalline Mn55Al45 alloys by Co addition

MnAl alloy (τ phase) is one of the most promising rare-earth-free permanent magnets due to its remarkable magnetic properties. The metastable τ phase is normally produced by rapid quenching technique and subsequent heat treatments. In this work, the direct formation of pure τ phase in (Mn0.55Al0.45)97Co3 alloy was achieved by using the melt-spinning process without heat treatments, which showed the magnetization of 5.0 × 105 A/m, coercivity of 125.6 kA/m and maximum energy product of 6.2 kJ/m3. It was found that the negative mixing enthalpy and the different atomic radius between Co and Mn, Al played a key role in improving the formation and stability of the τ phase in MnAlCo alloys. As a result, Co doping promoted the formation of and enhanced the stability of the τ phase in MnAl alloy. The present results will be helpful for the direct formation of ferromagnetic τ phase in MnAl rare-earth-free permanent magnet.

Comparative study of structural, electronic, optical and thermoelectric properties of GaS bulk and monolayer

ABSTRACTThe structural, electronic, optical properties of GaS in bulk and monolayer forms have been studied by means of full-potential linearised augmented plane wave calculations within framework of the density functional theory. Generalised gradient approximation and Tran–Blaha modified Becke–Johnson exchange potential (mBJ) were employed for the treatment of exchange-correlation effect in calculations. Our calculated lattice parameters are in good agreement with previous theoretical results and available experimental data. The negative formation enthalpy and cohesive energy indicate that both bulk and monolayer GaS can be synthesised and stabilised experimentally. Our electronic results show that the band gap of GaS monolayer is higher than that of bulk counterpart and strong hybridisation between electronic states of constituent atoms is observed in both cases. The optical properties such as reflectivity, absorption coefficient, refractive index and optical conductivity were derived from calculated complex dielectric function for wide energy range up to 35 eV. Finally, the thermoelectric properties of GaS bulk and monolayer also were calculated using semi-classical Boltzmann theory within the constant relaxation time approximation for investigating their applicability in thermoelectric devices.

Emulation of short-range ordering within the Compound Energy Formalism: Application to the calcite-magnesite solid solution

Modern thermodynamic assessment studies of multicomponent systems typically employ the Compound Energy Formalism (CEF) to describe phases of variable composition, which may show effects of chemical ordering. In CEF, the ordering is described by splitting a crystallographic site in which several components can substitute for each other into subsites (sublattices) and by allowing fractional occupancies of these subsites to vary. This type of component redistribution over subsites (sublattices) is classified in solid solution theories as long-range order (LRO). A well-known shortcoming of CEF is the absence of a direct description of the effects of short-range order (SRO), which do not involve a redistribution of components between sublattices, but reveal themselves in various modes of clustering. Here we show that SRO can be taken into account within CEF as an additional (fictive) LRO effect driven by an extra negative excess enthalpy term. We argue that the mathematical form of this term should be constrained such that it ensures its vanishing both in low- and high-temperature limits. Including such a term into CEF allows a significant improvement in the description of phase relations in the system of calcite-magnesite, CaCO3-MgCO3. The modified CEF model with SRO emulation is made available in the GEM-Selektor software.

An insight into the binding of 6-hydroxyflavone with hen egg white lysozyme: a combined approach of multi-spectroscopic and computational studies

The interaction of 6-hydroxyflavone (6HF) with hen egg white lysozyme (HEWL) has been executed using multi-spectroscopic and computational methods. Steady state fluorescence studies indicated that static quenching mechanism is involved in the binding of 6HF with HEWL, which was further supported by excited state lifetime and UV–vis absorption studies. The binding constant (Kb) of the HEWL–6HF complex was observed to be 6.44 ± 0.09 × 104 M−1 at 293 K, which decreases with the increase in temperature. The calculation of the thermodynamic quantities showed that the binding is exothermic in nature with a negative enthalpy change (ΔH = −11.91 ± 1.02 kJ mol−1) along with a positive entropy change (ΔS = +51.36 ± 2.43 J K−1 mol−1), and the major forces responsible for the binding are hydrogen bonding and hydrophobic interactions. The possibility of energy transfer from tryptophan (Trp) residue to the 6HF ligand was observed from Fo¨rster’s theory. The inclusion of 6HF within the binding site of HEWL induces some micro-environmental changes around the Trp residues as indicated by synchronous and three-dimensional (3D) fluorescence studies. The changes in secondary structural components of HEWL are observed on binding with 6HF along with a reduction in % α-helical content. Computational studies correlate well with the experimental finding, and the ligand 6HF is found to bind near to Trp 62 and Trp 63 residues of HEWL. Altogether, the present study provides an insight into the interaction dynamics and energetics of the binding of 6HF to HEWL.Communicated by Ramaswamy H. Sarma

Mechanical Properties, Electronic Structures, and Debye Temperature of NixBy Compounds Obtained by the First Principles Calculations

Mechanical properties, electronic properties, and Debye temperatures of NixBy (Ni3B, Ni2B, Ni4B3 and NiB) compounds were obtained by the first principles calculations based on the density functional theory (DFT). The results showed that the formation enthalpy of the NixBy compounds were stable with negative formation enthalpy. NiB had the largest B, G, and E, and the smallest υ; it also had the highest hardness (10.8 GPa) and Debye temperature (681.8 K). Ni4B3 had the strongest anisotropy. It was found that the valence bonds of the NixBy compounds studied were composed of both metal bond and covalent bond, and the mechanical properties and Debye temperature of the NixBy compounds increased with the increase of the B atomic ratio.

Determination of the Structural Changes Accompanying Binding of Protein S to Factor IXa

Background: Protein S (PS) is a 75-kDa, vitamin K-dependent anticoagulant that contains a Gla (enclosing γ-carboxyglutamic acids) module, a TSR (Thrombin Sensitive Region) module, four EGF (Epidermal Growth Factor)-like modules, and an SHBG (Sex Hormone Binding Globulin)-like region. Protein S deficiency is associated with risks for venous and arterial thrombosis, ischemic stroke, cerebral thrombophlebitis, myocardial infarction, and vascular calcification. Three disparate functions have been proposed for PS: (a) as a cofactor for active protein C; (b) as a cofactor of tissue factor pathway inhibitor, and (c) as a direct inhibitor of factor IXa. We have shown that PS binds FIXa with a Kd~40 nM. Currently, we are ascertaining the region and amino acid residues of FIXa that bind PS.Results and Discussion: We demonstrated before that lysine residue K126 and K132 of FIXa were very important in binding PS. However, there were no information regarding the change in the conformation of the complex when these residues were mutated. Here, we determined the structural changes in the complex by circular dichroism (CD), isothermal titration calorimetry (ITC), mass spectrometry, and molecular modeling to define the basis of the FIXa-PS interaction.The circular dichroism (CD) titration data of interaction between PS and FIXa showed the conformational change of PS due to interaction with FIXa. In addition, to understand the stability of the complex, we determined the α-helicity changes of PS in the presence and absence of FIXa. Initially, PS exhibited only a small amount of α-helical content (~3.5%) with a peak maxima at 214 nm in CD spectra. On addition of a minute amount of FIXa (50 nM), the PS CD spectra were blue-shifted by 4 nm and, simultaneously, increased in α-helical content by ~12%. The massive change in PS α-helical content on binding to FIXa directly revealed the stability of the complex. A similar interaction pattern was reflected in ITC experiments. The binding of PS with FIXa was essentially entropy-driven; binding was exothermic and favored by negative enthalpy and large positive entropy changes. The large positive entropy contribution to the binding may result from the disruption of water networks surrounding both proteins and a condensation of sodium and calcium ions from the polypeptide chains. Also, the negative Gibbs free energy change in binding revealed the spontaneous association between the two proteins.To achieve our goal of defining the amino acid interaction pattern of PS with FIXa, we combined liquid chromatography mass spectrometry (LCMS) and molecular modeling. To identify the residues involved in interaction, we subjected PS and FIXa, individually and in a complex, to a subtractive acetylation-protection assay. We used LCMS to compare the acetylated lysine residues in the individual proteins with the modified lysines in the complex.“ This methodology required normalization to lysine residues that were not acetylated. We found that lysine 126 (K126) and lysine 132 (K132) in FIXa were differentially protected in the complex about 2-fold compared with the free proteins. Our molecular modeling data also supported this mass spectrometric result. Modeling data pinpointed the regions of PS and FIXa that interact and revealed a major involvement of K132. To confirm the importance of K132, we analyzed by CD spectroscopy a derivative of FIXa in which K132 was changed to A132. We observed a dramatic reduction in interaction of the mutant FIXa with PSConclusion: Based on our preliminary data, we conclude that PS binds strongly with FIXa, and the complex is stabilized by a shift in α-helical content as shown in Figure 1.Figure.1 shows the CD spectral change of PS (curve 1, right panel) due to addition of different concentration of FIXa (curve 2-8, right panel). [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The electronic and elasticity properties of new half-metallic chalcogenides Cu3TMCh4 (TM = Cr, Fe and Ch = S, Se, Te): an ab initio study

ABSTRACTThe ternary copper-based chalcogenides Cu3TMCh4 (TM = Cr, Fe and Ch = S, Se, Te), which have simple cubic (SC) crystal structure and conform to space group with 215 space number, have been investigated by spin-polarised generalised gradient approximation (GGA) in the framework of density functional theory (DFT). All systems have been considered in ferromagnetic (FM) order. The mechanical and thermal properties and the electronic band structures of these systems have been investigated after the well-optimised structural parameters have been obtained. The spin-polarised electronic band structures of all the systems exhibit half-metallic behaviour with band gaps in minority spin channel from 0.29 eV for Cu3FeTe4 to 1.08 eV for Cu3CrS4, while metallic band structures are observed for majority spins. This agrees with the calculated total magnetic moments which are close to integer values. The calculated negative formation enthalpies indicate the energetic and thermodynamic stability of these compounds. Moreover, the calculated elastic constants verify that these materials are stable mechanically due to satisfying Born stability criteria. The estimated anisotropy shear factors show that Cu3FeS4, Cu3FeSe4 and Cu3CrSe4 systems have nearly isotropic character with 1.004, 0.910, and 0.958 values, respectively, whereas other compounds have relatively low anisotropic behaviour.

Hierarchical porous carbon from semi-coke via a facile preparation method for p-nitrophenol adsorption

Hierarchical porous carbon (PC) was prepared from semi-coke (SC) via a facile approach (K2CO3 catalytic steam activation) and used to adsorb p-nitrophenol (PNP) from aqueous solution. PC was characterized by elemental analysis, N2 adsorption-desorption, SEM, FT-IR spectra, Raman spectra, and XPS techniques. The results revealed that PC can process highly porous structures with a Brunauer–Emmett–Teller surface area of 121 m2 g−1. It is rich in oxygen functional groups on the surface and shows good affinity for p-nitrophenol, the maximum adsorption capacity being 192.13 mg g−1. Equilibrium adsorption data were fitted by the Langmuir, Freundlich, Redlich–Peterson, Liu, and Toth models. It was found that the Toth model presented the best fit. Kinetic studies showed that the data followed a pseudo second-order mode. Intra-particle diffusion studies showed that intra-particle diffusion was not the only rate controlling step. The negative enthalpy value ΔH° indicated that the adsorption process was exothermic. FT-IR and elemental analysis suggested that the adsorption mechanism of PNP onto PC was possible attributed to hydrogen bonding between polar functional groups on the PC surface and PNP. The spent PC was regenerated for four runs with acceptable adsorption capacity, which amounted to about 79.5% of the initial adsorption capacity. PC prepared from SC thus appears to be an effective adsorbent for removal of PNP from aqueous solutions.

Protein structure modification and allergenic properties of whey proteins upon interaction with tea and coffee phenolic compounds

Structural changes and allergenicity of whey proteins (WPI) upon complexation with caffeic acid (CA) and (-)-epigallocatechin gallate (EGCG) at acidic and neutral pH conditions were investigated. WPI-phenolic compounds interactions were evidenced by fluorescence quenching, accompanied by red-shift (32 nm in WPI-CA and 3 nm in WPI-EGCG). Negative exothermic enthalpy obtained by isothermal titration calorimetry analysis (–5966.4 ± 733.7 kJ/mol for WPI-CA and −14378.3 ± 2363.8 kJ/mol for WPI-EGCG) and reduction of surface hydrophobicity suggest that those interactions are of non-covalent nature. Additionally, changes in secondary structure pattern and increase in thermal stability were demonstrated by circular dichroism and were higher in neutral than in acidic conditions. WPI-EGCG complexes obtained in both pH conditions showed a reduced IgE-binding capacity to β-lg and BSA, two important allergens in milk. In conclusion, we suggest that complexation with EGCG could be a promising strategy to reduce the allergenicity of whey proteins.

Identification of nafamostat mesilate as an inhibitor of the fat mass and obesity-associated protein (FTO) demethylase activity

Nafamostat mesilate is a serine protease inhibitor and used for the treatment of pancreatitis and cancers. The fat mass and obesity-associated protein (FTO) was identified to be a demethylase and played an important role in physiological processes. The aim of this study was to examine the inhibition of Nafamostat mesilate on FTO demethylase activity. A combination of thermodynamic and enzymatic activity studies provides an insight into the recognition of Nafamostat mesilate by FTO. The binding of Nafamostat mesilate to FTO was driven by higher positive entropy changes and smaller negative enthalpy changes. The structural and thermodynamic information provides the basis for the design of more effective inhibitors for FTO. Our results might provide a novel target protein for Nafamostat mesilate.

Effect of Zr Addition on the Microstructure and Mechanical Properties of CoCrFeNiMn High-Entropy Alloy Synthesized by Spark Plasma Sintering.

As a classic high-entropy alloy system, CoCrFeNiMn is widely investigated. In the present work, we used ZrH2 powders and atomized CoCrFeNiMn powders as raw materials to prepare CoCrFeNiMnZrx (x = 0, 0.2, 0.5, 0.8, 1.0) alloys by mechanical alloying (MA), followed by spark plasma sintering (SPS). During the MA process, a small amount of Zr (x ≤ 0.5) can be completely dissolved into CoCrFeNiMn matrix, when the Zr content is above 0.5, the ZrH2 is excessive. After SPS, CoCrFeNiMn alloy is still as single face-centered cubic (FCC) solid solution, and CoCrFeNiMnZrx (x ≥ 0.2) alloys have two distinct microstructural domains, one is a single FCC phase without Zr, the other is a Zr-rich microstructure composed of FCC phase, B2 phase, Zr2Ni7, and σ phase. The multi-phase microstructures can be attributed to the large lattice strain and negative enthalpy of mixing, caused by the addition of Zr. It is worth noting that two types of nanoprecipitates (body-centered cubic (BCC) phase and Zr2Ni7) are precipitated in the Zr-rich region. These can significantly increase the yield strength of the alloys.

Containerless measurements of the liquid-state density of Ni–Al alloys for use as turbine blade materials

Ni–Al alloys are good candidate materials for the turbine blades of high-efficiency gas turbines. The thermophysical properties of the liquid alloy are required for accurate modeling of the casting process. In this study, the densities of liquid Ni–Al alloys were measured over the entire composition range using the electromagnetic levitation technique under a static magnetic field. Surface oscillation and translational motion of the electromagnetically levitated droplet are suppressed by the static magnetic field, so an accuracy density can be obtained using the technique under a static magnetic field. Before the measurements, the liquidus temperatures of Ni-rich alloys were determined by differential scanning calorimetry. The liquidus temperatures were used as temperature calibration for the density measurements. For all of the compositions, the densities were measured with an experimental uncertainty of less than 1.9%, and they are a linear function of the temperature. The excess volume of the liquid alloys has a minimum value at 50 mol% Ni. The results are discussed from the viewpoint of the thermodynamics. The Ni–Al system shows a large negative excess volume with large negative enthalpy of mixing and excess Gibbs energy.

Understanding the Stability of Salt-Inclusion Phases for Nuclear Waste-forms through Volume-based Thermodynamics

Formation enthalpies and Gibbs energies of actinide and rare-earth containing SIMs with silicate and germanate frameworks are reported. Volume-based thermodynamics (VBT) techniques complemented by density functional theory (DFT) were adapted and applied to these complex structures. VBT and DFT results were in closest agreement for the smaller framework silicate structure, whereas DFT in general predicts less negative enthalpies across all SIMs, regardless of framework type. Both methods predict the rare-earth silicates to be the most stable of the comparable structures calculated, with VBT results being in good agreement with the limited experimental values available from drop solution calorimetry.

Synthesis, characterization and unravelling the molecular interaction of new bioactive 4-hydroxycoumarin derivative with biopolymer: Insights from spectroscopic and theoretical aspect

In the progress of small molecule as drug candidates, 4-hydroxycoumarin based compounds bearing a crucial place as potent antibiotic agents with appreciable safety in drug invention. Being synthetically and easily obtainable, 4-hydroxycoumarin related compounds with planar structure have been promoted predominantly as DNA targeting agent. Nevertheless, here we elucidate the synthesis, characterization and theoretical study of bio-active small molecule 4-hydroxy-3,4′-bichromenyl-2,2′-dione (4HBD). Then we have illuminated the binding interactions of 4HBD with calf thymus DNA (ctDNA), which is particularly designed for biological application. Extensive investigations of the binding of 4HBD with ctDNA are provided by utilizing multi-spectroscopic and molecular docking approaches, including UV–vis absorbance, steady-state, time-resolved fluorescence spectroscopy and circular dichroism study. The calculated binding and quenching constant value from quantitative data analysis of absorption and emission spectroscopy shows that 4HBD binds to the ctDNA groove. Further confirmation of the same is found by comparative displacement and iodide quenching studies. Negative enthalpy, negative free energy and positive entropy change imply a hydrophobic force monitors the association of 4HBD with the biomacromolecule. Interestingly the small molecule (4HBD) shows potential anti-bacterial activity against the model pathogenic gram-negative (Escherichia coli and Pseudomonas aeruginosa) and gram-positive (Bacillus subtilis and Staphylococcus aureus) bacteria. The noncytotoxic nature of the 4HBD is demonstrated in vitro with the help of MTT assay by normal kidney epithelial (NKE), breast cancer cells (MCF-7) and human prostate cancer cell (PC3) lines. Hemolytic assay exhibits insignificant hemolysis of human erythrocyte cells at the minimum inhibitory concentration (MIC) of these tested bacteria. In this regard the present invention of 4-hydroxycoumarin based antimicrobial and noncytotoxic 4HBD molecule holds future promise in the development of new antibiotics.

Molecular interactions of AL3818 (anlotinib) to human serum albumin as revealed by spectroscopic and molecular docking studies

Anlotinib (ANB) is a novel member of the tyrosine kinase inhibitors approved for different types of cancer, its binding to human serum albumin (HSA) is of significant pharmacological importance. Hence, this study was devoted to understand the nature of the binding between ANB and HSA via the use of a set of conventional spectroscopic tools supplemented by molecular docking analysis. Fluorescence spectral measurements revealed a clear quenching effect of ANB on the HSA intrinsic fluorescence, which was shown to follow the static quenching type via the formation of a non-fluorescent complex. Analyses of this fluorescence data using the Stern–Volmer, Lineweaver-Burk and double-log relations showed that ANB-HSA binding constants ranged from 0.96 to 1.15 × 105 M−1 as resulted from the different relations in three different experimental temperatures. Further interpretation of the data using thermodynamic equations reveled spontaneous reaction between ANB and HSA with negative enthalpy and positive entropy values that propose the contribution of electrostatic forces possibly accompanied by hydrogen bonding. Docking studies confirmed the ANB-HSA complex formation with the ANB bound to Site I on the HSA structure mainly with the amino acid residues LYS 199, ARG 222, LEU 238 and ALA 291.