A series of novel α-furfuryl-2-alkylaminophosphonates have been efficiently synthesized from the one-pot three-component classical Kabachnik-Fields reaction in a green chemical approach by addition of an in situ generated dialkylphosphite to Schiff's base of aldehydes and amines by using environmental and eco-friendly silica gel supported iodine as a catalyst by microwave irradiation. The advantage of this protocol is simplicity in experimental procedures and products were resulted in high isolated yields. The synthesized α-furfuryl-2-alkylaminophosphonates were screened to in vitro antioxidant and plant growth regulatory activities and some are found to be potent with antioxidant and plant growth regulatory activities. These in vitro studies have been further supported by ADMET (absorption, distribution, metabolism, excretion, and toxicity), quantitative structure-activity relationship, molecular docking, and bioactivity studies and identified that they were potentially bound to the GLN340 amino acid residue in chain C of 1DNU protein and TYR597 amino acid residue in chain A of 4M7E protein, causing potential exhibition of antioxidant and plant growth regulatory activities. Eventually, title compounds are identified as good blood-brain barrier (BBB)-penetrable compounds and are considered as proficient central nervous system active and neuroprotective antioxidant agents as the neuroprotective property is determined with BBB penetration thresholds.
The title compound, C17H15N3O2, is a monoclinic polymorph (P21/c with Z' = 1) of the previously reported triclinic (P-1 with Z' = 2) form [Gajera et al. (2013 ▸). Acta Cryst. E69, o736-o737]. The mol-ecule in the monoclinic polymorph features a central pyrazolyl ring with an N-bound p-tolyl group and a C-bound 1,3-benzodioxolyl fused-ring system on either side of the C atom bearing the amino group. The dihedral angles between the central ring and the N- and C-bound rings are 50.06 (5) and 27.27 (5)°, respectively. The angle between the pendent rings is 77.31 (4)°, indicating the mol-ecule has a twisted conformation. The five-membered dioxolyl ring has an envelope conformation with the methyl-ene C atom being the flap. The relative disposition of the amino and dioxolyl substituents is syn. One of the independent mol-ecules in the triclinic form has a similar syn disposition but the other has an anti arrangement of these substituents. In the crystal structure of the monoclinic form, mol-ecules assemble into supra-molecular helical chains via amino-pyrazolyl N-H⋯N hydrogen bonds. These are linked into layers via C-H⋯π inter-actions, and layers stack along the a axis with no specific inter-actions between them.
The title compound, [Sn(CH3)2(C5H8NOS2)2], has the Sn(IV) atom bound by two methyl groups which lie over the weaker Sn-S bonds formed by two asymmetrically chelating di-thio-carbamate ligands so that the coordination geometry is skew-trapezoidal bipyramidal. The most prominent feature of the mol-ecular packing are secondary Sn⋯S inter-actions [Sn⋯S = 3.5654 (7) Å] that lead to centrosymmetric dimers. These are connected into a three-dimensional architecture via methyl-ene-C-H⋯S and methyl-C-H⋯O(morpholino) inter-actions. The Sn⋯S inter-actions are clearly evident in the Hirshfeld surface analysis of the title compound along with a number of other inter-molecular contacts.
The crystal and mol-ecular structures of two di-phenyl-tin bis-(di-thio-carbamate)s, [Sn(C6H5)2(C5H10NOS2)2], (I), and [Sn(C6H5)2(C7H14NO2S2)2], (II), are described. In (I), in which the metal atom lies on a twofold rotation axis, the di-thio-carbamate ligand coordinates with approximately equal Sn-S bond lengths and the ipso-C atoms of the Sn-bound phenyl groups occupy cis-positions in the resulting octa-hedral C2S4 donor set. A quite distinct coordination geometry is noted in (II), arising as a result of quite disparate Sn-S bond lengths. Here, the four S-donors define a trapezoidal plane with the ipso-C atoms lying over the weaker of the Sn-S bonds so that the C2S4 donor set defines a skewed trapezoidal bipyramid. The packing of (I) features supra-molecular layers in the ab plane sustained by methyl-ene-C-H⋯π(Sn-ar-yl) inter-actions; these stack along the c-axis direction with no specific inter-actions between them. In (II), supra-molecular chains along the b-axis direction are formed by methyl-ene-C-O(ether) inter-actions; these pack with no directional inter-actions between them. A Hirshfeld surface analysis was conducted on both (I) and (II) and revealed the dominance of H⋯H inter-actions contributing to the respective surfaces, i.e. >60% in each case, and other features consistent with the description of the mol-ecular packing above.
Two independent mol-ecules, A and B, comprise the asymmetric unit of the title compound, C20H21N3OSe. While the benzene ring directly bound to the central triazole ring is inclined to the same extent in both mol-ecules [dihedral angles = 40.41 (12) (mol-ecule A) and 44.14 (12)° (B)], greater differences are apparent in the dihedral angles between the Se-bound rings, i.e. 74.28 (12) (mol-ecule A) and 89.91 (11)° (B). Close intra-molecular Se⋯N inter-actions of 2.9311 (18) (mol-ecule A) and 2.9482 (18) Å (B) are noted. In the crystal, supra-molecular chains along the a axis are formed via O-H⋯N hydrogen bonding. These are connected into layers via C-H⋯O and C-H⋯N inter-actions; these stack along (01-1) without directional inter-molecular inter-actions between them.
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.
In search of better α-glucosidase inhibitors, a series of bis-indolylmethane sulfonohydrazides derivatives (1-14) were synthesized and evaluated for their α-glucosidase inhibitory potential. All derivatives exhibited outstanding α-glucosidase inhibition with IC50 values ranging between 0.10 ± 0.05 to 5.1 ± 0.05 μM when compared with standard drug acarbose having IC50 value 856.28 ± 3.15 μM. Among the series, analog 7 (0.10 ± 0.05 μM) with tri-chloro substitution on phenyl ring was identified as the most potent inhibitor of α-glucosidase (∼ 8500 times). The structure activity relationship has been also established. Molecular docking studies were also performed to help understand the binding interaction of the most active analogs with receptors. From the docking studies, it was observed that all the active bis-indolylmethane sulfonohydrazides derivatives showed considerable binding interactions within the active site (acarbose inhibition site) of α-glucosidase. We also evaluated toxicity of all derivatives and found none of them are toxic.
We report on the assembly of three-fold axially compressed icosahedral arrays of the bowl shaped p-sulfonatocalix[4]arene molecules in the solid-state, intricately bound to dipicolinate and yttrium(iii) ions, with the compression reflected in Hirshfeld surface analyses. Solution studies show dissolution of the icosahedra intact, but with a geometrical rearrangement to regular icosahedra.
This article aims to discuss (1) the incorrect identification of Cr(III) and Cr(VI) binding energies in the Cr 2p XPS (X-ray photoelectron spectroscopy) spectra of the laden adsorbent (the nZVI-BC sample after Cr(VI) adsorption), (2) misconception regarding the Weber-Morris intraparticle diffusion model, and (3) inconsistency between the experiential data and the Thomas adsorption rate constants. The authors hope that our comments are beneficial for other researchers to avoid the undesirable mistakes.
The application of protein-protein interaction (PPI) has been widely used in various industries, such as food, nutraceutical, and pharmaceutical. A deeper understanding of PPI is needed, and the molecular forces governing proteins and their interaction must be explained. The design of new structures with improved functional properties, e.g., solubility, emulsion, and gelation, has been fueled by the development of structural and colloidal building blocks. In this review, the molecular forces of protein structures are discussed, followed by the relationship between molecular force and structure, ways of a bind of proteins together in solution or at the interface, and functional properties. A more detailed look is thus taken at the relationship between the various influencing factors on molecular forces involved in PPI. These factors include protein properties, such as types, concentration, and mixing ratio, and solvent conditions, such as ionic strength and pH. This review also summarizes methods tha1t are capable of identifying molecular forces in protein and PPI, as well as characterizing protein structure.
In order to invent a porcine gelatine detection device using microbial resources, bacterial enzymes with a preference towards porcine gelatine and their candidate genes were evaluated. Five (n = 5) bacterial strains isolated from hot spring water and wet clay, Malaysia were screened for their gelatinase activity. The gelatinase enzyme was extracted and purified using ammonium sulphate precipitation prior to performing gelatinase assay on porcine, bovine and fish gelatine medium substrates. The G2 strain or Enterobacter aerogenes (Strain EA1) was selected for whole genome sequenced after showing a consistent trend of preference towards porcine gelatine. The gelatinase candidate gene gelEA1_9 was cloned and expressed. Based on one-way analysis of variance (ANOVA) with POST-HOC Duncan test (α = 0.05), the final product of gelEA1_9 was identified as a novel gelatinase. This gelatinase presented no significant difference in activity towards porcine gelatine. Hence, the present study demonstrated an enzyme-substrate interaction for porcine gelatine identification.
In this work, a chitosan-modified nanofiber membrane was fabricated and used to examine the permeation characteristics of C-phycocyanin (CPC) obtained from Spirulina platensis. The effects of NaCl concentration (0.1-1.0 M), chitosan coupling pH (6-8), chitosan coupling concentration (0.1-3.0%), algal solution pH (6-8), algal mass concentration (0.1-1.0% dw/v), and membrane flux (4.08 × 10-2-2.04 × 10-1 mL/min·cm2) on the penetration performance of the membrane for CPC were investigated. The results show that the order of binding selectivity of the membrane for these proteins is contaminating proteins (TP) > allophycocyanin (APC) > CPC. TP and APC molecules were more easily adsorbed by the chitosan-modified membrane, and the CPC molecules most easily penetrated the membrane without being adsorbed, enhancing CPC purity. The purification factor and total mass flux were 3.3 fold and 66%, respectively, in a single step.
Tyrphostin 9 (Tyr 9) is a potent platelet-derived growth factor receptor (PDGFR) inhibitor, which induces apoptosis in various cancer cell types. The binding of Tyr 9 to the major transport protein, human serum albumin (HSA) was investigated using several spectroscopic techniques and molecular docking method. Fluorescence quenching titration results showed progressive decrease in the protein fluorescence with increasing drug concentrations. A decreasing trend of the Stern-Volmer constant, Ksv with increasing temperature characterized the drug-induced quenching as static quenching, thus pointed towards the formation of Tyr 9-HSA complex. The binding constant of Tyr 9-HSA interaction was found to lie within the range 3.48-1.69 × 105 M-1 at three different temperatures, i.e. 15 °C, 25 °C and 35 °C, respectively and suggested intermediate binding affinity between Tyr 9 and HSA. The drug-HSA complex seems to be stabilized by hydrophobic forces, van der Waals forces and hydrogen bonds, as suggested from the thermodynamic data as well as molecular docking results. The far-UV and the near-UV CD spectral results showed slight alteration in the secondary and tertiary structures, respectively, of the protein upon Tyr 9 binding. Interaction of Tyr 9 with HSA also produced microenvironmental perturbations around protein fluorophores, as evident from the three-dimensional fluorescence spectral results but increased protein's thermal stability. Both competitive drug binding results and molecular docking analysis suggested Sudlow's Site I of HSA as the preferred Tyr 9 binding site. Communicated by Ramaswamy H. Sarma.
The high dependency and surplus use of agrochemical products have liberated enormous quantities of toxic halogenated pollutants into the environment and threaten the well-being of humankind. Herein, this study performed molecular docking, molecular dynamic (MD) simulations, molecular mechanics-Poisson Boltzmann Surface Area (MM-PBSA) calculations on the DehH2 from Bacillus thuringiensis, to identify the order of which the enzyme degrades different substrates, haloacids, haloacetate and chlorpyrifos. The study discovered that the DehH2 favored the degradation of haloacids and haloacetates (-3.3 - 4.6 kcal/mol) and formed three hydrogen bonds with Asp125, Arg201 and Lys202. Despite the inconclusive molecular docking result, chlorpyrifos was consistently shown to be the least favored substrate of the DehH2 in MD simulations and MM-PBSA calculations. Results of MD simulations revealed the DehH2-haloacid- (RMSD 0.15 - 0.25 nm) and DehH2-haloacetates (RMSF 0.05 - 0.25 nm) were more stable, with the DehH2-L-2CP complex being the most stable while the least was the DehH2-chlorpyrifos (RMSD 0.295 nm; RMSF 0.05 - 0.59 nm). The Molecular Mechanics Poisson-Boltzmann Surface Area calculations showed the DehH2-L-2CP complex (-24.27 kcal/mol) having the lowest binding energy followed by DehH2-MCA (-22.78 kcal/mol), DehH2-D-2CP (-21.82 kcal/mol), DehH2-3CP (-21.11 kcal/mol), DehH2-2,2-DCP (-18.34 kcal/mol), DehH2-2,3-DCP (-8.34 kcal/mol), DehH2-TCA (-7.62 kcal/mol), while chlorpyrifos was unable to spontaneously bind to DehH2 (+127.16 kcal/mol). In a nutshell, the findings of this study offer valuable insights into the rational tailoring of the DehH2 for expanding its substrate specificity and catalytic activity in the near future.Communicated by Ramaswamy H. Sarma.
Aptamers are a class of folded nucleic acid strands capable of binding to different target molecules with high affinity and selectivity. Over the years, they have gained a substantial amount of interest as promising molecular tools for numerous medical applications, particularly in targeted therapeutics. However, only the different treatment approaches and current developments of aptamer-drug therapies have been discussed so far, ignoring the crucial technical and functional aspects of constructing a therapeutically effective aptamer-driven drug delivery system that translates to improved in-vivo performance. Hence, this paper provides a comprehensive review of the strategies used to improve the therapeutic performance of aptamer-guided delivery systems. We focus on the different functional features such as drug deployment, payload capacity, in-vivo stability and targeting efficiency to further our knowledge in enhancing the cell-specific delivery of aptamer-drug conjugates. Each reported strategy is critically discussed to emphasize both the benefits provided in comparison with other similar techniques and to outline their potential drawbacks with respect to the molecular properties of the aptamers, the drug and the system to be designed. The molecular architecture and design considerations for an efficient aptamer-based delivery system are also briefly elaborated.
The commutativity degree is the probability that a pair of elements chosen randomly from a group commute. The concept of commutativity degree has been widely discussed by several authors in many directions. One of the important generalizations of commutativity degree is the probability that a random element from a finite group G fixes a random element from a non-empty set S that we call the action degree of groups. In this research, the concept of action degree is further studied where some inequalities and bounds on the action degree of finite groups are determined. Moreover, a general relation between the action degree of a finite group G and a subgroup H is provided. Next, the action degree for the direct product of two finite groups is determined. Previously, the action degree was only de?ned for ?nite groups, the action degree for ?nitely generated groups will be de?ned in this research and some bounds on them are going to be determined.
Neoculin is a sweet protein capable to alter the sour taste into sweet taste, it is 500 times sweeter than the ordinary sugar. This protein has been discovered in Malaysia under the name of Curculin. There are a number of experimental studies that have been conducted on neoculin but none of the studies focuses on molecular level, in order to understand how the protein interacts with the human sweet taste receptors T1R2 and T1R3. Therefore, in this work, a protein-protein docking study was performed between neoculin and the human sweet taste receptor T1R2 and T1R3. The docking results showed residues that might be important for binding the neoculin with the human sweet taste receptors, particularly T1R3 at the amino terminal domain (ATD). In addition, the current results showed that His11, which is important for the taste modifying ability does not bind directly to the human sweet taste receptors.
The present study reported a facile method for the determination of melamine in milk powder products based on the aggregation of reactant-free 5 nm gold nanoparticles (AuNPs). The strong electrostatic attraction between the positively charged exocyclic amine groups present in the melamine molecule and the negatively charged ions bound to the AuNPs induced aggregation of the AuNPs, resulting in visible color changes that could be seen with the naked eye and monitored by ultraviolet-visible (UV-Vis) absorbance spectra. The method shows high sensitivity with detection limits of 1 × 10-9 M for visual detection and 1 × 10-11 M for UV-Vis analysis, which is far below the safety limit of melamine ingestion in infant formula (1 ppm = 7.9 × 10-6 M) and the detection limit acquired by most AuNP-based melamine detection methods. Good recoveries were obtained over the range of 94.7-95.5% with a relative standard deviation of mean recovery (RSD) ranging from 1.40 to 5.81. The method provides a simple, feasible, fast and real-time detection of melamine adulterants in infant formula by the naked eye, without the aid of advanced instruments.
Clinacanthus nutans has been reported to have many medicinal properties and it is traditionally used in treating viral lesions. This study aims to determine the molecular docking of C. nutans compounds detected by Gas Chromatography-Mass Spectrometry (GC-MS) with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 main protease) protein and its host receptor angiotensin-converting enzyme 2 (ACE2) protein using the AutoDock 4.2 tool. The drug-likeness and molecular docking analyses showed that fourteen compounds of C. nutans satisfied the Lipinski's rule of five and they exhibited good inhibitory effects against the SARS-Cov-2 main protease and ACE2 proteins. In addition, the glyceryl 2-linolenate compound was found to have the most potent binding affinities with both proteins. The results provide useful insights into the molecular inhibitory interactions of C. nutans compounds detected by GC-MS analysis with the targeted SARS-CoV-2 main protease and ACE2 protein.