On the growth and approximation of entire functions represented by Laplace–Stieltjes’ transformation

In the present paper, we obtain the characterization of various growth parameters of an entire function F(s) represented by Laplace–Stieltjes transformation in terms of the rate of decrease of \(E_n ( {F,\beta } ),\)where \(E_n ( {F,\beta } )\) represents the error in approximating the function F(s) by exponential polynomials.     

Synthesis and applications of copillar[5]arene dithiols

Abstract

A novel copillar[4+1]arene incorporating alkylthiol substituents was synthesised in three steps and structurally characterised as the first example of a pillar[n]arene to incorporate two terminal thiols on the same aromatic ring. The macrocycle was attached to gold electrodes through a standard dipping technique. Cyclic voltammetry demonstrated selectivity for Li⁺ over other alkali metal cations. The copillar[4+1]arene was also used as a capping agent in the preparation of 3 nm gold nanoparticles.     

Phytocannabinoid Compositions from Cannabis Act Synergistically with PARP1 Inhibitor against Ovarian Cancer Cells In Vitro and Affect the Wnt Signaling Pathway

Ovarian cancer (OC) is the single most lethal gynecologic malignancy. Cannabis sativa is used to treat various medical conditions, and is cytotoxic to a variety of cancer types. We sought to examine the effectiveness of different combinations of cannabis compounds against OC. Cytotoxic activity was determined by XTT assay on HTB75 and HTB161 cell lines. Apoptosis was determined by flow cytometry. Gene expression was determined by quantitative PCR and protein localization by confocal microscopy. The two most active fractions, F5 and F7, from a high Δ9–tetrahydrocannabinol (THC) cannabis strain extract, and their standard mix (SM), showed cytotoxic activity against OC cells and induced cell apoptosis. The most effective phytocannabinoid combination was THC+cannabichromene (CBC)+cannabigerol (CBG). These fractions acted in synergy with niraparib, a PARP inhibitor, and were ~50-fold more cytotoxic to OC cells than to normal keratinocytes. The F7 and/or niraparib treatments altered Wnt pathway-related gene expression, epithelial–mesenchymal transition (EMT) phenotype and β-catenin cellular localization. The niraparib+F7 treatment was also effective on an OC patient’s cells. Given the fact that combinations of cannabis compounds and niraparib act in synergy and alter the Wnt signaling pathway, these phytocannabinoids should be examined as effective OC treatments in further pre-clinical studies and clinical trials.     

Evaluation of binary QSAR models derived from LUDI and MOE scoring functions for structure based virtual screening

In today's world of high-throughput in silico screening, the development of virtual screening methodologies to prioritize small molecules as new chemical entities (NCEs) for synthesis is of current interest. Among several approaches to virtual screening, structure-based virtual screening has been considered the most effective. However the problems associated with the ranking of potential solutions in terms of scoring functions remains one of the major bottlenecks in structure-based virtual screening technology. It has been suggested that scoring functions may be used as filters for distinguishing binders from nonbinders instead of accurately predicting their binding free energies. Subsequently, several improvements have been made in this area, which include the use of multiple rather than single scoring functions and application of either consensus or multivariate statistical methods or both to improve the discrimination between binders and nonbinders. In view of it, the discriminative ability (distinguishing binders from nonbinders) of binary QSAR models derived using LUDI and MOE scoring functions has been compared with the models derived by Jacobbsson et al. on five data sets viz. estrogen receptor alphamimics (ERalpha_mimics), estrogen receptor alphatoxins (ERalpha_toxins), matrix metalloprotease 3 inhibitors (MMP-3), factor Xa inhibitors (fXa), and acetylcholine esterase inhibitors (AChE). The overall analyses reveal that binary QSAR is comparable to the PLS discriminant analysis, rule-based, and Bayesian classification methods used by Jacobsson et al. Further the scoring functions implemented in LUDI and MOE can score a wide range of protein-ligand interactions and are comparable to the scoring functions implemented in ICM and Cscore. Thus the binary QSAR models derived using LUDI and MOE scoring functions may be useful as a preliminary screening layer in a multilayered virtual screening paradigm.     

The link between sequence and conformation in protein structures appears to be stereochemically established

In search of the link between sequence and conformation in protein structures, we perform molecular dynamics analysis of the effect of stereochemical mutation in end-protected octa-alanine Ac-Ala8-NHMe from poly-L to an alternating-L,D structure. The mutation has a dramatic effect, transforming the peptide from a condition of extreme sensitivity to one of extreme insensitivity to solvent. Examining the molecular folds of poly-L and alternating-L,D structure in atomistic detail, we find them to differ in the relationship between peptide dipolar interactions at the local and nonlocal levels, either conflicting or harmonious depending upon the chain stereochemistry. The stereochemical transformation of interpeptide electrostatics from a condition of conflict to one of harmony explains the long-standing puzzle of why poly-L and alternating-L,D peptides strongly differ in properties such as "stiffness" and solvent sensitivity. Furthermore, it is possible that poly-L stereochemistry is also the fulcrum of protein sensitivity to the effects of amino acid side-chain structures via dielectric arbitrations in interpeptide electrostatics. Indeed the evidence is accumulating that the amino acid side chains differing in alpha-helix and beta-sheet propensities also differ in their desolvating effects in the adjacent and nearest-neighbor peptides and thus possibly in the solvent screening of peptide dipolar interactions.     

Application of Doehlert design in optimizing the determination of degraded products of nerve agents by ion-pair liquid chromatography electrospray ionization tandem mass spectrometry

A qualitative method was developed for the determination of degraded products of nerve agents by using ion-pair liquid chromatography electrospray ionization tandem mass spectrometry (IP-LC-ESI-MS(n)). Generally, alkylphosphonic acids (APAs) and O-alkyl alkylphosphonic acids (AAPAs) give deprotonated molecular ion [M-H](-) in negative mode. Interestingly, first time we obtained the molecular radical anion [M](.-) of phosphonic acids in negative mode by using tri-n-butyl amine as an ion-pairing agent. We interpreted this observation as an indication of electrochemical reduction of phosphonic acids in electrospray needle. Three variables such as sheath gas flow, electrospray needle voltage and pH of the mobile phase were investigated to enhance the molecular radical anion [M](.-) signal of each analyte. The Doehlert design was used to obtain the region in which the optimum value of such variables is simultaneously achieved. Limit of detection achieved was 0.5 microg mL(-1) for AAPAs and 10 microg mL(-1) for APAs. Excellent precision was observed with less than 8.61% RSD. Finally, the method was applied for the detection of ethyl methylphosphonic in aqueous extract of soil sample.     

Kinetics of the simultaneous oxidation of nickel(II) and sulfur(IV) by oxygen in alkaline medium in Ni(II)–sulfur(IV)–O2 system

In the Ni(II)–S(IV)–O₂ system in the region of pH > 8.4, both Ni(II) and S(IV) are simultaneously autoxidized, and when sulfur is consumed fully NiOOH precipitates. At pH > 8.4, ethanol has no effect on the rate, whereas ammonia strongly inhibits the reaction when pH > 7.0. The kinetics of the reaction, in both the presence and the absence of ethanol, is defined by the rate law where k is the rate constant, K_O is the equilibrium constant for the adsorption of O₂ on ? Ni(OH)₂ particle surface. In ammonia buffer, the factor F is defined by where K, K_OH, K₁, K₂, K₃, and K₄ are the stability constants of NiSO₃, NiOH⁺, Ni(NH₃)²⁺, Ni(NH₃), Ni(NH₃), and Ni(NH₃), respectively. In unbuffered medium, the factor F reduces to The values of k and K^sp were found to be (1.3 ± 0.08) × 10^?1 s^?1 and (4.2 ± 3.5) × 10^?16, respectively, at 30°C. A nonradical mechanism that assumes the adsorption of both SO₃^2? and O₂ on the ? Ni(OH)₂ particle surface has been proposed. At pH ≤ 8.2, Ni(II) displays no catalytic activity for sulfur(IV)‐autoxidation and it is also not oxidized to NiOOH. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 464–478, 2010     

Development and validation of rapid ion-pair RPLC method for simultaneous determination of certain B-complex vitamins along with vitamin C

A rapid, simple, and accurate ion-pair RPLC method has been developed for simultaneous analysis of vitamin C and major B-complex vitamins. An RP C18 column thermostated at 30 degrees C was used with gradient elution of mobile phase comprising 10 mM potassium dihydrogen phosphate buffer (containing 3 mM sodium hexane-1-sulfonate, adjusted to pH 2.80 with o-phosphoric acid) and methanol at a flow rate of 1.0 mL/min to achieve the best possible separation and resolution of all vitamins in about 11.00 min. The detection was performed at 274 nm. The method has been implemented successfully for simultaneous determination of vitamins present in 12 multivitamin/multimineral pharmaceutical preparations, as well as in human urine. Typical validation characteristics were evaluated in accordance with International Conference on Harmonization guidelines. Good linearity over the investigated concentration levels was observed. Intraday repeatability was < or = 2.0%, and interday variation was < or = 2.6%, for all vitamins. The method can be used for assay of these vitamins over a wide concentration range with good precision and accuracy; hence, it would be appropriate for routine QC as well as in clinical analysis.