Synthesis,DFT Calculations,Antiproliferative, Bactericidal Activity and Molecular Docking of Novel Mixed-Ligand Salen/8-Hydroxyquinoline Metal Complexes

Despite the common use of salens and hydroxyquinolines as therapeutic and bioactive agents, their metal complexes are still under development. Here, we report the synthesis of novel mixed-ligand metal complexes (MSQ) comprising salen (S), derived from (2,2′-{1,2-ethanediylbis[nitrilo(E) methylylidene]}diphenol, and 8-hydroxyquinoline (Q) with Co(II), Ni(II), Cd(II), Al(III), and La(III). The structures and properties of these MSQ metal complexes were investigated using molar conductivity, melting point, FTIR, ¹H NMR, ¹³C NMR, UV–VIS, mass spectra, and thermal analysis. Quantum calculation, analytical, and experimental measurements seem to suggest the proposed structure of the compounds and its uncommon monobasic tridentate binding mode of salen via phenolic oxygen, azomethine group, and the NH group. The general molecular formula of MSQ metal complexes is [M(S)(Q)(H₂O)] for M (II) = Co, Ni, and Cd or [M(S)(Q)(Cl)] and [M(S)(Q)(H₂O)]Cl for M(III) = La and Al, respectively. Importantly, all prepared metal complexes were evaluated for their antimicrobial and anticancer activities. The metal complexes exhibited high cytotoxic potency against human breast cancer (MDA-MB231) and liver cancer (Hep-G2) cell lines. Among all MSQ metal complexes, CoSQ and LaSQ produced IC₅₀ values (1.49 and 1.95 µM, respectively) that were comparable to that of cisplatin (1.55 µM) against Hep-G2 cells, whereas CdSQ and LaSQ had best potency against MDA-MB231 with IC₅₀ values of 1.95 and 1.43 µM, respectively. Furthermore, the metal complexes exhibited significant antimicrobial activities against a wide spectrum of both Gram-positive and -negative bacterial and fungal strains. The antibacterial and antifungal efficacies for the MSQ metal complexes, the free S and Q ligands, and the standard drugs gentamycin and ketoconazole decreased in the order AlSQ > LaSQ > CdSQ > gentamycin > NiSQ > CoSQ > Q > S for antibacterial activity, and for antifungal activity followed the trend of LaSQ > AlSQ > CdSQ > ketoconazole > NiSQ > CoSQ > Q > S. Molecular docking studies were performed to investigate the binding of the synthesized compounds with breast cancer oxidoreductase (PDB ID: 3HB5). According to the data obtained, the most probable coordination geometry is octahedral for all the metal complexes. The molecular and electronic structures of the metal complexes were optimized theoretically, and their quantum chemical parameters were calculated. PXRD results for the Cd(II) and La(III) metal complexes indicated that they were crystalline in nature.     

Analysis of five HMG-CoA reductase inhibitors-- atorvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin: pharmacological, pharmacokinetic and analytical overview and development of a new method for use in pharmaceutical formulations analysis and in vitro metabolism studies

A specific, accurate, precise and reproducible high-performance liquid chromatographic (HPLC) method was developed and validated for the simultaneous quantitation of five 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, viz. atorvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin, in pharmaceutical formulations and extended the application to in vitro metabolism studies of these statins. Ternary gradient elution at a flow rate of 1 mL/min was employed on an Intertisl ODS 3V column (4.6 x 250 mm, 5 microm) at ambient temperature. The mobile phase consisted of 0.01 m ammonium acetate (pH 5.0), acetonitrile and methanol. Theophylline was used as an internal standard (IS). The HMG-CoA reductase inhibitors and their metabolites were monitored at a wavelength of 237 nm. Drugs were found to be 89.6-105.6% of their label's claim in the pharmaceutical formulations. For in vitro metabolism studies the reaction mixtures were extracted with simple liquid-liquid extraction using ethyl acetate. Baseline separation of statins and their metabolites along with IS free from endogenous interferences was achieved. Nominal retention times of IS, atorvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin were 7.5, 17.2, 21.6, 28.5, 33.5 and 35.5 min, respectively. The proposed method is simple, selective and could be applicable for routine analysis of HMG-CoA reductase inhibitors in pharmaceutical preparations as well as in vitro metabolism studies.     

Numerical and analytical solutions of an ODE: Strengths and weaknesses of the analytical series solution

The analytical solution for a nonlinear ordinary differential equation was obtained but was only applicable for lower input parameters. A numerical solution for the same equation which provided good results for all input parameters was also obtained. Since the analytical solution contained an infinite series, the solution depended on the number of terms used in the series, resulting in failure for certain input parameters at low time values.     

Best proximity point theorems in the frameworks of fairly and proximally complete spaces

Let us contemplate the problem of solving the linear or non-linear equations of the form \(Tx=gx\) in the framework of metric space. When T is a non-self mapping and g is a self-mapping, it may cause the non-existence of a solution to the preceding equation. At this juncture, one is of course interested in computing an approximate solution \(x^*\) in the space such that \(Tx^*\) is as close to \(gx^*\) as possible. To be precise, if T is from A to B and g is from A to A, where A and B are subsets of a metric space, one is concerned with the computation of a global minimizer of the mapping \(x\longrightarrow d(gx, Tx)\) which serves as a measure of closeness between Tx and gx. This paper is concerned with the resolution of the aforesaid global minimization problem if T is a proximal contraction and g is an isometry in the frameworks of fairly and proximally complete spaces.     

Nanocellulose for biosorption of chlorpyrifos from water: chemometric optimization,kinetics and equilibrium

The study explores the biosorption potential of nanocellulose (NC) to remove an insecticide, chlorpyrifos (CP), from aqueous solutions using the batch method. Biosorption kinetics were very fast and reached equilibrium in 60 min, and the experimental kinetic data had fit well with the pseudo-second-order model. Film diffusion was the rate-limiting step for the biosorption of CP onto crystalline nanocellulose (CNC). The equilibrium sorption was well described by the Sips and Langmuir isotherm models. The values of maximum sorption capacities (7.237–5.017 mg/g for the Sips and 12.325–7.247 mg/g for the Langmuir model) decreased with an increase in temperature from 288 to 308 K, signifying biosorption of CP is an exothermic process. Based on the central composite design (CCD), two-factor interaction (2FI) and quadratic models, the correlation between the effects of variable parameters on the CP biosorption onto NC was evaluated. The chemometric analyses suggested that 1.5 g/l NC required 20 min to biosorb 5 mg/l CP to yield an efficiency of 99.3%. Overall, the results demonstrated that NCs can be a promising biosorbent for the removal of pesticides from aqueous streams.     

"Click"-capture, ring-opening metathesis polymerization (ROMP), release: facile triazolation utilizing ROMP-derived oligomeric phosphates

Soluble, high-load ring-opening metathesis polymerization (ROMP)-derived oligomeric triazole phosphates (OTP) are reported for application as efficient triazolating reagents of nucleophilic species. Utilizing a "Click"-capture, ROMP, release protocol, the efficient and purification-free, direct triazolation of N-, O-, and S-nucleophilic species was successfully achieved. A variety of OTP derivatives were rapidly synthesized as free-flowing solids on a multigram scale from commercially available materials.     

The Design of α/β‐Peptides: Study on Three‐Residue Turn Motifs and the Influence of Achiral Glycine on Helix and Turn

Novel three‐residue helix‐turn secondary structures, nucleated by a helix at the N terminus, were generated in peptides that have ‘β‐Caa‐L ‐Ala‐L ‐Ala,’ ‘β‐Caa‐L ‐Ala‐γ‐Caa,’ and ‘β‐Caa‐L ‐Ala‐δ‐Caa’ (in which β‐Caa is C‐linked carbo‐β‐amino acid, γ‐Caa is C‐linked carbo‐γ‐amino acid, and δ‐Caa is C‐linked carbo‐δ‐amino acid) at the C terminus. These turn structures are stabilized by 12‐, 14‐, and 15‐membered (mr) hydrogen bonding between NH(i)/CO(i+2) (i+2 is the last residue in the peptide) along with a 7‐mr hydrogen bond between CO(i)/NH(i+2). In addition, a series of α/β‐peptides were designed and synthesized with alternating glycine (Gly) and (S)‐β‐Caa to study the influence of an achiral α‐residue on the helix and helix‐turn structures. In contrast to previous results, the three ‘β–α–β’ residues at the C terminus (α‐residue being Gly) are stabilized by only a 13‐mr forward hydrogen bond, which resembles an α‐turn. Extensive NMR spectroscopic and molecular dynamics (MD) studies were performed to support these observations. The influence of chirality and side chain is also discussed.     

Photopolymerization of Acrylonitrile by Potassium TrisoxalatocobaItate(III) in Aqueous Perchloric Acid

Results of a kinetic study on photopolymerization of acrylonitrile by potassium trisoxalatocobaltate(II1) in aqueous perchloric acid medium (pH = 1) by use of light of 365 nm wavelength at 30 |Mg 0.1°C are presented. All reactions were carried out under completely deaerated conditions. Certain important features of the photopolymerization are described. The rate of polymerization R_p was followed by gravimetric estimation of polymer formed and rate of disappearance of complex - R_c by spectrocolorometric estimation of complex disappearing. R_p was found to be directly proportional to [M]^3/2, k_ε ^1/2, and I^1/2, where P[M], k_ε, and I refer to concentration of acrylonitrile, light absorption fraction of the complex, and light intensity, respectively. -R_c was found to be directly proportional to k_ε and I. A reaction scheme is drawn and kinetic expressions derived on the basis of that scheme are given.