Transition metal chalcogenides (TMCs) have gained worldwide interest owing to their outstanding renewable energy conversion capability. However, the poor mechanical flexibility of most existing TMCs limits their practical commercial applications. Herein, triggered by the recent and imperative synthesis of highly ductile α-Ag2S, an effective approach based on evolutionary algorithm and ab initio total-energy calculations for determining stable, ductile phases of bulk and two-dimensional Ag x Se1-x and Ag x Te1-x compounds was implemented. The calculations correctly reproduced the global minimum bulk stoichiometric P212121-Ag8Se4 and P21/c-Ag8Te4 structures. Recently reported metastable AgTe3 was also revealed but it lacks dynamical stability. Further single-layered screening unveiled two new monolayer P4/nmm-Ag4Se2 and C2-Ag8Te4 phases. Orthorhombic Ag8Se4 crystalline has a narrow, direct band gap of 0.26 eV that increases to 2.68 eV when transforms to tetragonal Ag4Se2 monolayer. Interestingly, metallic P21/c-Ag8Te4 changes to semiconductor when thinned down to monolayer, exhibiting a band gap of 1.60 eV. Present findings confirm their strong stability from mechanical and thermodynamic aspects, with reasonable Vickers hardness, bone-like Young's modulus (E) and high machinability observed in bulk phases. Detailed analysis of the dielectric functions ε(ω), absorption coefficient α(ω), power conversion efficiency (PCE) and refractive index n(ω) of monolayers are reported for the first time. Fine theoretical PCE (SLME method ∼11-28%), relatively high n(0) (1.59-1.93), and sizable α(ω) (104-105 cm-1) that spans the infrared to visible regions indicate their prospects in optoelectronics and photoluminescence applications. Effective strategies to improve the temperature dependent power factor (PF) and figure of merit (ZT) are illustrated, including optimizing the carrier concentration. With decreasing thickness, ZT of p-doped Ag-Se was found to rise from approximately 0.15-0.90 at 300 K, leading to a record high theoretical conversion efficiency of ∼12.0%. The results presented foreshadow their potential application in a hybrid device that combines the photovoltaic and thermoelectric technologies.
Molecular dynamics reaction simulation showed that the rate constant is not constant over the concentration profile of reactants and products over a fixed temperature regime, and this variation is expressed in terms of the defined reactivity coefficients. The ratio of these coefficients for the forward and backward reactions were found to equal that of the activity coefficient ratio for the product and reactant species. A theory was developed to explain kinetics in general based on these observations. Several other theorems had first to be developed, most striking of all was the inference that the excess Helmholtz free energy was the thermodynamical function which had a direct relation to these activity factors than the Gibbs free energy. The theory is applied to a class of ionic reactions which could not be rationalized using the standard Bjørn-Bjerrum theory of ionic reactions.
Isonicotinamide-4-methoxybenzoic acid co-crystal (1), C6H6N2O·C8H8O3, is formed through slow evaporation from methanol solution and it undergoes a first-order isosymmetry (monoclinic I2/a ↔ monoclinic I2/a) structural phase transition at Tc= 142.5 (5) K, which has been confirmed by an abrupt jump of crystallographic interaxial angle β from variable-temperature single-crystal XRD and small heat hysteresis (6.25 K) in differential scanning calorimetry measurement. The three-dimensional X-ray crystal structures of (1) at the low-temperature phase (LTP) (100, 140 and 142 K) and the high-temperature phase (HTP) (143, 150, 200, 250 and 300 K) were solved and refined as a simple non-disordered model with final R[F2> 2σ(F2)] ≃ 0.05. The asymmetric unit of (1) consists of crystallographically independent 4-methoxybenzoic acid (A) and isonicotinamide (B) molecules in both enantiotropic phases. Molecule A adopts a `near-hydroxyl' conformation in which the hydroxyl and methoxy groups are positioned on the same side. Both `near-hydroxyl' and `near-carbonyl' molecular conformations possess minimum conformational energies with an energy difference of
The performance of aptamers as versatile tools in numerous analytical applications is critically dependent on their high target binding specificity and selectivity. However, only the technical or methodological aspects of measuring aptamer-target binding affinities are focused, ignoring the equally important mathematical components that play pivotal roles in affinity measurements. In this study, we aim to provide a comprehensive review regarding the utilization of different mathematical models and equations, along with a detailed description of the computational steps involved in mathematically deriving the binding affinity of aptamers against their specific target molecules. Mathematical models ranging from one-site binding to multiple aptameric binding site-based models are explained in detail. Models applied in several different approaches of affinity measurements such as thermodynamics and kinetic analysis, including cooperativity and competitive-assay based mathematical models have been elaborately discussed. Mathematical models incorporating factors that could potentially affect affinity measurements are also further scrutinized.
Free laccase and fungal biomass from white-rot fungi were compared in the thermokinetics study of the laccase-catalyzed decolorization of an azo dye, i.e., Trypan Blue. The decolorization in both systems followed a first-order kinetics. The apparent first-order rate constant, k1', value increases with temperature. Apparent activation energy of decolorization was similar for both systems at ∼ 22 kJ mol(-1), while energy for laccase inactivation was 18 kJ mol(-1). Although both systems were endothermic, fungal biomass showed higher enthalpy, entropy, and Gibbs free energy changes for the decolorization compared to free laccase. On the other hand, free laccase showed reaction spontaneity over a wider range of temperature (ΔT = 40 K) as opposed to fungal biomass (ΔT = 15 K). Comparison of entropy change (ΔS) values indicated metabolism of the dye by the biomass.
The ability of non-living biomass of an arsenic-hypertolerant Bacillus cereus strain SZ2 isolated from a gold mining environment to adsorb As (III) from aqueous solution in batch experiments was investigated as a function of contact time, initial As (III) concentration, pH, temperature and biomass dosage. Langmuir model fitted the equilibrium data better in comparison to Freundlich isotherm. The maximum biosorption capacity of the sorbent, as obtained from the Langmuir isotherm, was 153.41 mg/g. The sorption kinetic of As (III) biosorption followed well the pseudo-second-order rate equation. The Fourier transform infrared spectroscopy analysis indicated the involvement of hydroxyl, amide and amine groups in As (III) biosorption process. Field emission scanning electron microscopy-energy dispersive X-ray analysis of the non-living B. cereus SZ2 biomass demonstrated distinct cell morphological changes with significant amounts of As adsorbed onto the cells compared to non-treated cells. Desorption of 94 % As (III) was achieved at acidic pH 1 showing the capability of non-living biomass B. cereus SZ2 as potential biosorbent in removal of As (III) from arsenic-contaminated mining effluent.
The potential of quaternized wood (QW) chips in removing hexavalent chromium from synthetic solution and chrome waste under both batch and continuous-flow conditions was investigated. Sorption was found to be dependent on pH, metal concentration, and temperature. QW chips provide higher sorption capacity and wider pH range compared with untreated wood chips. The equilibrium data could be fitted into the Langmuir isotherm model, and maximum sorption capacities were calculated to be 27.03 and 25.77 mg/g in synthetic chromate solution and chrome waste, respectively. The presence of sulfate in high concentration appeared to suppress the uptake of chromium by QW chips. Column studies showed that bed depth influenced the breakthrough time greatly whereas flow rate of influent had little effect on its sorption on the column.
Hydrolysis of palm oil has become an important process in Oleochemical industries. Therefore, an investigation was carried out for hydrolysis of palm oil to fatty acid and glycerol using immobilized lipase in packed bed reactor. The conversion vs. residence time data were used in Michaelis-Menten rate equation to evaluate the kinetic parameters. A mathematical model for the rate of palm oil hydrolysis was proposed incorporating role of external mass transfer and pore diffusion. The model was simulated for steady-state isothermal operation of immobilized lipase packed bed reactor. The experimental data were compared with the simulated results. External mass transfer was found to affect the rate of palm oil hydrolysis at higher residence time.
Despite an exponential increase in computing power over the past decades, present information technology falls far short of expectations in areas such as cognitive systems and micro robotics. Organisms demonstrate that it is possible to implement information processing in a radically different way from what we have available in present technology, and that there are clear advantages from the perspective of power consumption, integration density, and real-time processing of ambiguous data. Accordingly, the question whether the current silicon substrate and associated computing paradigm is the most suitable approach to all types of computation has come to the fore. Macromolecular materials, so successfully employed by nature, possess uniquely promising properties as an alternate substrate for information processing. The two key features of macromolecules are their conformational dynamics and their self-assembly capabilities. The purposeful design of macromolecules capable of exploiting these features has proven to be a challenge, however, for some groups of molecules it is increasingly practicable. We here introduce an algorithm capable of designing groups self-assembling of nucleic acid molecules with multiple conformational states. Evaluation using natural and artificially designed nucleic acid molecules favours this algorithm significantly, as compared to the probabilistic approach. Furthermore, the thermodynamic properties of the generated candidates are within the same approximation as the customised trans-acting switching molecules reported in the laboratory.
Biosorption process is a promising technology for the removal of heavy metals from industrial wastes and effluents using low-cost and effective biosorbents. In the present study, adsorption of Pb(2+), Cu(2+), Fe(2+), and Zn(2+) onto dried biomass of red seaweed Kappaphycus sp. was investigated as a function of pH, contact time, initial metal ion concentration, and temperature. The experimental data were evaluated by four isotherm models (Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich) and four kinetic models (pseudo-first-order, pseudo-second-order, Elovich, and intraparticle diffusion models). The adsorption process was feasible, spontaneous, and endothermic in nature. Functional groups in the biomass involved in metal adsorption process were revealed as carboxylic and sulfonic acids and sulfonate by Fourier transform infrared analysis. A total of nine error functions were applied to validate the models. We strongly suggest the analysis of error functions for validating adsorption isotherm and kinetic models using linear methods. The present work shows that the red seaweed Kappaphycus sp. can be used as a potentially low-cost biosorbent for the removal of heavy metal ions from aqueous solutions. Further study is warranted to evaluate its feasibility for the removal of heavy metals from the real environment.
Despite the reported association of adiponectin receptor 1 (ADIPOR1) gene mutations with vulnerability to several human metabolic diseases, there is lack of computational analysis on the functional and structural impacts of single nucleotide polymorphisms (SNPs) of the human ADIPOR1 at protein level. Therefore, sequence- and structure-based computational tools were employed in this study to functionally and structurally characterize the coding nsSNPs of ADIPOR1 gene listed in the dbSNP database. Our in silico analysis by SIFT, nsSNPAnalyzer, PolyPhen-2, Fathmm, I-Mutant 2.0, SNPs&GO, PhD-SNP, PANTHER, and SNPeffect tools identified the nsSNPs with distorting functional impacts, namely, rs765425383 (A348G), rs752071352 (H341Y), rs759555652 (R324L), rs200326086 (L224F), and rs766267373 (L143P) from 74 nsSNPs of ADIPOR1 gene. Finally the aforementioned five deleterious nsSNPs were introduced using Swiss-PDB Viewer package within the X-ray crystal structure of ADIPOR1 protein, and changes in free energy for these mutations were computed. Although increased free energy was observed for all the mutants, the nsSNP H341Y caused the highest energy increase amongst all. RMSD and TM scores predicted that mutants were structurally similar to wild type protein. Our analyses suggested that the aforementioned variants especially H341Y could directly or indirectly destabilize the amino acid interactions and hydrogen bonding networks of ADIPOR1.
The presence of at least two ionizable active center groups has been detected by a study of the effect of pH upon catalysis of hydrolysis of L-alanyl-beta-naphthylamide by human liver alanine aminopeptidase and upon the inhibition of hydrolysis by inhibitors and substrate analogs. Octanoic acid, octylamine, and peptide inhibitors have been found to be competitive inhibitors and are therefore thought to bind the active center. L-Phe was previously shown to bind the active center since it was found to be a competitive inhibitor of the hydrolysis of tripeptide substrates (Garner, C. W., and Behal, F. J. (1975), Biochemistry 14, 3208). A plot of pKm vs. pH for the substrate L-Ala-beta-naphthylamide showed that binding decreased below pH 5.9 and above 7.5, the points at which the theoretical curve undergoes an integral change in slope. These points are interpreted as the pKa either of substrate ionizable groups or binding-dependent enzyme active center groups. Similar plots of pKm vs. pH for L-alanyl-p-nitroanilide (as substrate) and pKi vs. pH for L-Leu-L-Leu-L-Leu and D-Leu-L-Tyr (as inhibitors) gave pairs fo pKa values of 5.8 and 7.4, 6.0 and 7.5, and 5.7 and 7.5, respectively. All the above substrates (and D-Leu-L-Tyr) have pKa values near 7.5; therefore, the binding-dependent group with a pKa value near 7.5 is possibly this substrate group. Similar plots of pKi vs. pH for the inhibitors L-Phe, L-Met, L-Leu, octylamine, and octanoic acid had only one bending point at 7.7, 7.6, 7.4, 6.3, and 5.9, respectively. Amino acid inhibitors, octylamine, and octanoic acid have no groups with pKa values between 5 and 9. These data indicate that there are two active center ionizable groups with pKa values of approximately 6.0 and 7.5 which are involved in substrate binding or inhibitory amino acid binding but not in catalysis since Vmax was constant at all pH values tested.
Finding a proper transition structure for the peptide bond formation process can lead one to a better understanding of the role of ribosome in catalyzing this reaction. Using computer simulations, we performed the potential energy surface scan on the ester bond dissociation of P-site aminoacyl-tRNA and the peptide bond formation of P-site and A-site amino acids. The full fragments of initiator tRNA(i)(met) and elongator tRNA(phe) are attached to both cognate and non-cognate amino acids as the P-site substrate. The A-site amino acid for all four calculations is methionine. We used ONIOM calculations to reduce the computational cost. Our study illustrates the reduced rate of peptide bond formation for misacylated tRNA(i)(met) in the absence of ribosomal bases. The misacylated elongator tRNA(phe), however, did not show any difference in its PES compared with that for the phe-tRNA(phe). This demonstrates the structural specification of initiator tRNA(i)(met) for the amino acids side chain.
The fundamental mechanism of biochemistry lies on the reaction kinetics, which is determined by the reaction pathways. Interestingly, the reaction pathway is a challenging concept for undergraduate students. Experimentally, it is difficult to observe, and theoretically, it requires some degree of physics knowledge, namely statistical and quantum mechanics. However, students can utilize computational methods to study the reaction kinetics without paying too much attention but not wholly neglecting the comprehension of physics. We hereby provided an approach to study the reaction kinetics based on density-functional calculations. We particularized the study of the isomerization case involving five molecules at three different temperatures and emphasized the importance of the transition state in the study of reaction kinetics. The results we presented were in good agreement with the experiments and provided useful insights to assist students in the application of their knowledge into their research.
Heliotropium is one of the most important plant genera to have conventional folklore importance, and hence is a potential source of bioactive compounds. Thus, the present study was designed to explore the therapeutic potential of Heliotropium crispum Desf., a relatively under-explored medicinal plant species. Methanolic extracts prepared from a whole plant of H. crispum were studied for phytochemical composition and possible in vitro and in silico biological properties. Antioxidant potential was assessed via six different assays, and enzyme inhibition potential against key clinical enzymes involved in neurodegenerative diseases (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)), diabetes (α-amylase and α-glucosidase), and skin problems (tyrosinase) was assayed. Phytochemical composition was established via determination of the total bioactive contents and reverse phase ultra-high performance liquid chromatography mass spectrometry (RP-UHPLC-MS) analysis. Chemical profiling revealed the tentative presence of 50 secondary metabolites. The plant extract exhibited significant inhibition against AChE and BChE enzymes, with values of 3.80 and 3.44 mg GALAE/g extract, respectively. Further, the extract displayed considerable free radical scavenging activity against DPPH and ABTS radicals, with potential values of 43.19 and 41.80 mg TE/g extract, respectively. In addition, the selected compounds were then docked against the tested enzymes, which have shown high inhibition affinity. To conclude, H. crispum was found to harbor bioactive compounds and showed potent biological activities which could be further explored for potential uses in nutraceutical and pharmaceutical industries, particularly as a neuroprotective agent.
The present article describes the synthesis, in vitro urease inhibition and in silico molecular docking studies of a novel series of bi-heterocyclic bi-amides. The synthesis of title compounds was initiated by benzoylation, with benzoyl chloride (1), of the key starter ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate (2) in weak basic aqueous medium followed by hydrazide formation, 4, and cyclization with CS2 to reach the parent bi-heterocyclic nucleophile, N-{4-[(5-sulfanyl-1,3,4-oxadiazol-2-yl)methyl]-1,3-thiazol-2-yl}benzamide (5). Various electrophiles, 8a-l, were synthesized by a two-step process and these were finally coupled with 5 to yield the targeted bi-heterocyclic bi-amide molecules, 9a-l. The structures of the newly synthesized products were corroborated by IR, 1H NMR, 13C NMR, EI-MS and elemental analysis. The in vitro screening of these molecules against urease explored that most of the compounds exhibit potent inhibitory potential against this enzyme. The compound 9j, with IC50 value of 2.58 ± 0.02 µM, exhibited most promising inhibitory activity among the series, relative to standard thiourea having IC50 value of 21.11 ± 0.12 µM. In silico studies fully augmented the experimental enzyme inhibition results. Chemo-informatics analysis showed that synthesized compounds (9a-l) mostly obeyed the Lipinski's rule. Molecular docking study suggested that ligand 9j exhibited good binding energy value (-7.10 kcal/mol) and binds within the active region of target protein. So, on the basis of present investigation, it was inferred that 9j may serve as a novel scaffold for designing more potent urease inhibitors.
In recent decade, the entrance of α-N-heterocyclic thiosemicarbazones derivates (Triapne, COTI-2 and DpC) in clinical trials for cancer and HIV-1 has vastly increased the interests of medicinal chemists towards this class of organic compounds. In the given study, a series of eighteen new (3a-r) 3-ethoxy salicylaldehyde-based thiosemicarbazones (TSC), bearing aryl and cycloalkyl substituents, were synthesized and assayed for their pharmacological potential against carbonic anhydrases (hCA I and hCA II), cholinesterases (AChE and BChE) and α-glycosidase. The hCA I isoform was inhibited by these novel 3-ethoxysalicylaldehyde thiosemicarbazone derivatives (3a-r) in low nanomolar levels, the Ki of which differed between 144.18 ± 26.74 and 454.92 ± 48.32 nM. Against the physiologically dominant isoform hCA II, the novel compounds demonstrated Kis varying from 110.54 ± 14.05 to 444.12 ± 36.08 nM. Also, these novel derivatives (3a-r) effectively inhibited AChE, with Ki values in the range of 385.38 ± 45.03 to 983.04 ± 104.64 nM. For BChE was obtained with Ki values in the range of 400.21 ± 35.68 to 1003.02 ± 154.27 nM. For α-glycosidase the most effective Ki values of 3l, 3n, and 3q were with Ki values of 12.85 ± 1.05, 16.03 ± 2.84, and 19.16 ± 2.66 nM, respectively. Moreover, the synthesized TCSs were simulated using force field methods whereas the binding energies of the selected compounds were estimated using MM-GBSA method. The findings indicate the present novel 3-ethoxy salicylaldehyde-based thiosemicarbazones to be excellent hits for pharmaceutical applications.
Odanacatib (ODN) is a selective cathepsin K inhibitor that acts as an anti-resorptive agent to treat osteoporosis. ODN is also found effective in reducing the effect of severe periodontitis. The interaction between ODN and human serum albumin (HSA) was investigated using spectroscopic, microscopic, and in silico approaches to characterize their binding. The fluorescence intensity of HSA increased upon the addition of increasing concentrations of ODN accompanied by blueshift in the fluorescence spectrum, which suggested hydrophobic formation around the microenvironment of the fluorophores upon ODN binding. A moderate binding affinity was obtained for ODN-HSA binding, with binding constant (Ka) values of ∼104 M-1. Circular dichroism results suggested that the overall secondary and tertiary structures of HSA were both only slightly altered upon ODN binding. The surface morphology of HSA was also affected upon ODN binding, showing aggregate formation. Drug displacement and molecular docking results revealed that ODN preferably binds to site III in subdomain IB of HSA, while molecular dynamics simulations indicated formation of a stable protein complex when site III was occupied by ODN. The ODN-HSA complex was mainly stabilized by a combination of hydrogen bonding, hydrophobic interactions, and van der Waals forces. These findings provide additional information to understand the interaction mechanism of ODN in blood circulation and may help in future improvements on the adverse effects of ODN.
Biodiesel with improved yield was produced from microalgae biomass under simultaneous cooling and microwave heating (SCMH). Nannochloropsis sp. and Tetraselmis sp. which were known to contain higher lipid species were used. The yield obtained using this novel technique was compared with the conventional heating (CH) and microwave heating (MWH) as the control method. The results revealed that the yields obtained using the novel SCMH were higher; Nannochloropsis sp. (83.33%) and Tetraselmis sp. (77.14%) than the control methods. Maximum yields were obtained using SCMH when the microwave was set at 50°C, 800W, 16h of reaction with simultaneous cooling at 15°C; and water content and lipid to methanol ratio in reaction mixture was kept to 0 and 1:12 respectively. GC analysis depicted that the biodiesel produced from this technique has lower carbon components (<19 C) and has both reasonable CN and IV reflecting good ignition and lubricating properties.
Sunflower seed oil residue, a by-product of sunflower seed oil refining, was utilized as a feedstock for preparation of activated carbon (SSHAC) via microwave induced K(2)CO(3) chemical activation. SSHAC was characterized by Fourier transform infrared spectroscopy, nitrogen adsorption-desorption and elemental analysis. Surface acidity/basicity was examined with acid-base titration, while the adsorptive properties of SSHAC were quantified using methylene blue (MB) and acid blue 15 (AB). The monolayer adsorption capacities of MB and AB were 473.44 and 430.37 mg/g, while the Brunauer-Emmett-Teller surface area, Langmuir surface area and total pore volume were 1411.55 m(2)/g, 2137.72 m(2)/g and 0.836 cm(3)/g, respectively. The findings revealed the potential to prepare high surface area activated carbon from sunflower seed oil residue by microwave irradiation.