Quantitative Structure–Retention Relationships as Useful Tool to Characterize Chromatographic Systems and Their Potential to Simulate Biological Processes

Quantitative structure–retention relationships (QSRR) date back to the 1970s and are associated with the evolution of modern Chromatography, while in conjunction with quantitative structure–property relationships (QSPR), they make part of the QSAR discipline. The present review offers a survey of QSRR from a medicinal chemistry point of view, highlighting the merits of this approach in exploiting the friendly chromatographic techniques for the establishment of the physico chemical profiling of drug and drug candidates. It starts with a short overview on QSRR methodology concerning molecular representation, statistical tools and model validation. It continues focusing on the major recent achievements of QSRR with regard to the characterization of chromatographic systems and thereupon to the improvement of stationary phases and to experimental design, while emphasizing their application in drug design. The inter-relation of retention with lipophilicity, a property of paramount interest in drug action and the merit of biomimetic chromatography and of MEEKC systems to simulate essential pharmacokinetic properties are commented under the insights offered by QSRR, in conjunction with QSPR. Characteristic examples are discussed.     

Study of the Chromatographic Behavior of Selected Steroid Hormones on Aluminum Oxide Plates Based on Quantitative Structure—Retention Relationships

JPC – Journal of Planar Chromatography – Modern TLC - The chromatographic properties of eight steroids: trans-androsterone, methyltestosterone, testosterone, progesterone, cortisone,...     

Determination of Indicator Congeners of Polychlorinated Biphenyls in Water at Ultratrace Levels by Gas Chromatography–Tandem Mass Spectrometry

Journal of Analytical Chemistry - We validated a procedure for the determination of indicator congeners (ICs) of polychlorinated biphenyls (PCBs) (IUPAC nos. 28, 52, 101, 118, 138, 153, and 180) in...     

Quantitative Structure—Retention Relationships of Some Steroid and Phenanthrene Derivatives on Cyano-, Reversed-Phase,and Normal-Phase Thin-Layer Chromatography Stationary Phases

JPC – Journal of Planar Chromatography – Modern TLC - In the presented study, quantitative structure—retention relationships (QSRR) methodology was used to investigate the...     

Gas Chromatographic Determination of Poly(3‐hydroxybutyrate) with Alkaline Hydrolysis and Acid Esterification

Abstract

A new pretreatment method for the gas chromatographic determination of poly(3‐hydroxybutyrate) (PHB) was developed based on a combination of alkaline hydrolysis and acid esterification. The determination principle is as follows: PHB is hydrolyzed to its monomer 3‐hydroxybutyrate by alkaline solution, followed by the esterification with methanol to generate the methyl ester of 3‐hydroxybutyrate catalyzed by acid, which is detected by a gas chromatography. From the comparison of effects of alkali and acid on PHB hydrolysis and 3‐hydroxybutyrate esterification, alkali resulted in a better performance for the hydrolysis, while acid was better for the esterification. The pretreatment conditions for PHB were optimized and the determination performance was characterized.     

Structure and Energetics of β–Diketonates. XI. Molecular Structure of Sc(thd)3 from Gas–Phase Electron Diffraction Data

Electron–diffraction and mass–spectrometric studies of saturated vapor of scandium tris–dipivaloyl–methanate showed that at 135(5)°, the vapor contains only monomeric Sc(thd)₃, whose structural parameters r _a , r _g , and r were determined. The internuclear distances in the chelate ring were found to be rSc=O) = 2.066(5), r(O=C) = 1.272(3), and r(C=C_r) = 1.385(3). The ScO₆ coordination polyhedron has a D ₃ symmetry configuration close to a regular antiprism. The angle of rotation of the O=O=O trigonal faces relative to their position in a regular prism is 25.7(1.5)°.     

Applications of Gas Chromatography–Mass Spectrometry (GC–MS): An Examination of Selected African Cases

As a result of the new economic order in Africa, scientists face enormous challenges due to an increase in socio and economic activities. Gas chromatography–mass spectrometry (GC–MS) will be expected to play a big role in providing some of the solutions to the challenges. Up to now, applications of GC–MS in Africa have focused on profiling natural products for their chemical composition as seen from the number of papers published between 2005 and 2011, i.e. at approximately 62 % of the total. In order to meet the new challenges, a paradigm shift is suggested in the design of research projects. Some economic activities envisaged to boom are food and beverage production for local consumption and for export to markets in the developed world. To meet the requirements of these markets, monitoring pesticides and metabolites of veterinary drugs and other toxins in food will become paramount. Africa also needs to put stringent environmental monitoring policies in place. This will aid remediation following accidental or intentional spillages of chemicals not benign to the environment.

     

Ring-Opening 1,3-Aminochalcogenation of Donor–Acceptor Cyclopropanes: A Three-Component Approach

A 1,3-aminothiolation was realized by reacting 2-substituted cyclopropane 1,1-dicarboxylates with sulfonamides and N-(arylthio)succinimides. Under Sn(OTf)₂ catalysis the transformation proceeded smoothly to the corresponding ring-opened products bearing the sulfonamide in the 1-position next to the donor and the arylthio residue in the 3-position next to the acceptor. The procedure was extended to the corresponding selenium analogues by employing N-(phenylseleno)succinimides as an electrophilic selenium source.     

A Benzimidazole-pyridine-2,3-dicarboxylic Acid Bridged Zinc(Ⅱ) Coordination Complex–crystal Structure,Quantum Chemistry and Luminescence

The structure of a zinc(Ⅱ) coordination complex(1), [C_(14) H_(10) N_3 O_5 Zn_(1.5)]_n or [Zn_(1.5)(bzim)(pydc)(H_2 O)]_n(H_2 pydc = pyridine-2,3-dicarboxylic acid, Hbzim = benzimidazole), has been determined by X-ray crystallography and characterized by elemental analysis, IR spectrum and luminescence. Chemical formula: C_(14) H_(10) N_3 O_5 Zn_(1.5). It crystallizes in the monoclinic system, space group P2_1/c with a = 12.303(4), b = 12.052(4), c = 10.212(3) ?, β = 104.147(4), V = 1468.3(8) ?~3, Z = 4, M_r = 398.30, D_c = 1.802 g/cm~3, F(000) = 800, μ = 2.501 mm-1 and S = 1.000. The 2-D network architecture of 1 is constructed from benzimidazole, zinc and pyridine-2,3-dicarboxylic acid. The quantum-chemical calculations have been performed on ‘molecular fragments' extracted from the crystal structure using the B3 LYP method in Gaussian 09. The luminescence spectrum shows that complex 1 emits blue luminescence.     

Structural Stability Among Hybrid Antimicrobial Peptide Cecropin A(1–8)–Magainin 2(1–12) and Its Analogues: A Computational Approach

Cecropin A–Magainin 2 (CA–MA) hybrid antimicrobial peptide (AMP), a combination of two naturally occurring AMPs, cecropin A and magainin 2 is preferred widely in biotechnological, nano and pharmaceutical applications. It exhibits a strong antibacterial activity with a characteristic reduced cytotoxic effect towards mammalian cells. In this study, three AMP structures native CA–MA hybrid and its tryptophan substitutes CA–MA L2 and CA–MA A2 was computationally studied to analyze their structural stability and functionality. Computational analysis like, intra-molecular interactions (25), relative stability (3.22) and instability index (?14.28) showed an increase in structural stability of native CA–MA hybrid. Additionally, the generated peptide ensembles showed a RMSD (3.98 Å), RMSF (0.202 Å), radius of gyration (11.98 Å), ovality (3.33) and hydrophobicity (69.7%) supporting native CA–MA along with hydrogen bond strength (?4.212 kcal/mol) and distribution comparatively. The distribution of secondary structure in native CA–MA hybrid showed the sequential maintenance of stable helical content along with helical stability (52.25%) and computed free energy (?1.74 kcal/mol) in membrane mimicking environment proving its functional activity comparatively. This study aids in designing stable AMP biodrugs with low cytotoxicity in future, the result can be potentially extended to other AMPs to assist in their exploitation as peptide and nano drugs.     

A Molecular Modeling for the Complexation of Cyclobis(paraquat-p-phenylene) with Substituted Benzenes and Biphenyls

The molecular recognition of cyclobis(paraquat-p-phenylene), 14+, has drawn great attention recently, due to its important applications in the design and synthesis of electrochemically and chemically switchable rotaxanes, photoactive rotaxanes, and other molecular devices1. Usually, this type of molecular recognition was investigated with the methods including X-ray, NMR, UV, and IR. However, since these methods usually have difficulties in providing a detailed understanding of the energeti…     

Lewis-base Adducts of Lead(Ⅱ) Compounds: Synthesis, Structure and Quantum Chemistry Calculation of Mononuclear Pb(phen)(SCN)2

1 INTRODUCTION [(phen)2Pb(NCS)(O2NO)][14] and Pb(phen)3 (SCN)2 .[15] We report and compare herein the synthesis and The coordination chemistry of lead(II) with N structural characterization of a novel lead thiocya-donor ligands has been widely investigated in the nate adduct with unusual four coordination Pb(II).past decade and frequently discussed with regard tothe stereochemical activity of valence shell lone elec- 2 EXPERIMENTALtron pairs[1～5]. The building of new molecule…     

Switchable Nonlinear Optical Properties of η(5)-Monocyclopentadienylmetal Complexes: A DFT Approach

Density functional theory (DFT) calculations have been carried out to investigate the switching of the second-order nonlinear optical (NLO) properties of η(5)-monocyclopentadienyliron(II) and ruthenium(II) model complexes presenting 5-(3-(thiophen-2-yl)benzo[c]thiophen-1-yl)thiophene-2-carbonitrile as a ligand. The switching properties were induced by redox means. Both oxidation and reduction stimulus have been considered, and calculations have been performed both for the complexes and for the free benzo[c]thiophene derivative ligand in order to elucidate the role played by the organometallic fragment on the second-order NLO properties of these complexes. B3LYP, CAM-B3LYP, and M06 functionals were used for our calculations. The results show some important structural changes upon oxidation/reduction that are accompanied by significant differences on the corresponding second-order NLO properties. TD-DFT calculations show that these differences on the second-order NLO response upon oxidation/reduction are due to a change in the charge transfer pattern, in which the organometallic iron and ruthenium moieties play an important role. The calculated static hyperpolarizabilities were found to be strongly functional dependent. CAM-B3LYP, however, seems to predict more reliable structural and optical data as well as hyperpolarizabilities when compared to experimental data. The use of this functional predicts that the studied complexes can be viewed as acting as redox second-order NLO switches, in particular using oxidation stimulus. The β(tot) value of one-electron oxidized species is at least ～8.3 times (for Ru complex) and ～5.5 times (for Fe complex) as large as that of its nonoxidized counterparts.     

Improved Synthesis of (–)-Agelastatin A

Optimization of key steps in the synthesis of the architecturally unique tetracyclic antitumor alkaloid (–)-agelastatin A (1) improved the overall yield of the 11-step process (eight operations) from 9% to 23%. Changing the solvent and using a more efficient N-benzyl deprotecting-group procedure enhanced the yields of the C-ring and D-ring intermediates, (–)-4 and (–)-7, respectively. Bromination of (–)-7 with 1,3-dibromo-5,5-dimethylhydantoin, rather than N-bromosuccinimide (NBS), increased the yield of (–)-1 from 69% to more than 94% yield.