Experimental verification of halomethyl carbinol synthesis from carbonyl compounds using a TiCl-Mg bimetallic complex promoter.

A critical evaluation of the feasibility of a previously published method for synthesising halomethyl carbinols from carbonyl compounds and CHBr or CHCl using a bimetallic TiCl-Mg complex is presented. The synthesis of compounds lacking the -CH- group in their structure was achieved by following the procedures proposed in the reference literature or by introducing modifications to selected process parameters. These compounds were not identified as expected β-halohydrins but as products of reductive dimerisation or subsequent pinacolic rearrangement of carbonyl substrates.

Computational Modeling of Gold Nanoparticle Interacting with Molecules of Pharmaceutical Interest in Water.

We derived a theory of biomolecule binding to the surface of Au clusters and of the Au plane based on the hard soft acid base (HSAB) principle and the free electron metallic surface model. With the use of quantum mechanical calculations, the chemical potential () and the chemical hardness () of the biomolecules are estimated. The effect of the gold is introduced via the empirical value of the gold chemical potential (-5.

Thiogenistein-Antioxidant Chemistry, Antitumor Activity, and Structure Elucidation of New Oxidation Products.

Isoflavonoids such as genistein (GE) are well known antioxidants. The predictive biological activity of structurally new compounds such as thiogenistein (TGE)-a new analogue of GE-becomes an interesting way to design new drug candidates with promising properties. Two oxidation strategies were used to characterize TGE oxidation products: the first in solution and the second on the 2D surface of the Au electrode as a self-assembling TGE monolayer.

Structure-Activity Relationship of Hydroxycinnamic Acid Derivatives for Cooperating with Carnosic Acid and Calcitriol in Acute Myeloid Leukemia Cells.

Plant phenolic compounds have shown the ability to cooperate with one another at low doses in producing enhanced anticancer effects. This may overcome the limitations (e.g.

Unexpected Reaction Products of Uracil and Its Methyl Derivatives with Acetic Anhydride and Methylene Chloride.

New acetyl derivatives of uracil, 6-methyluracil, and thymine were obtained in the course of an unconventional synthesis in methylene chloride. It was shown that products with the acetyloxymethyl fragment are formed according to a mechanism different from that for products with the acetyloxyethyl group. In particular, for uracil it was proven that the reaction with AcO, TEA, and CHCl leads to 1-acetyloxymethyluracil, where the substituent is composed of the -CH- fragment that originated from CHCl and the 1-acetyloxy moiety from AcO.

Anti-Cancer and Electrochemical Properties of Thiogenistein-New Biologically Active Compound.

Pharmacological and nutraceutical effects of isoflavones, which include genistein (GE), are attributed to their antioxidant activity protecting cells against carcinogenesis. The knowledge of the oxidation mechanisms of an active substance is crucial to determine its pharmacological properties. The aim of the present work was to explain complex oxidation processes that have been simulated during voltammetric experiments for our new thiolated genistein analog (TGE) that formed the self-assembled monolayer (SAM) on the gold electrode.

Evaluation of tramadol human pharmacokinetics and safety after co-administration of magnesium ions in randomized, single- and multiple-dose studies.

Background: Magnesium ions (Mg) increase and prolong opioid analgesia in chronic and acute pain. The nature of this synergistic analgesic interaction has not yet been explained. Our aim was to investigate whether Mg alter tramadol pharmacokinetics.

Synthesis of Thiol Derivatives of Biological Active Compounds for Nanotechnology Application.

An efficient method of thiol group introduction to the structure of common natural products and synthetic active compounds with recognized biological efficacy such genistein (), 5,11-dimethyl-5-indolo[2,3-b]quinolin (), capecitabine (), diosgenin (), tigogenin (), flumethasone (), fluticasone propionate (), ursolic acid methyl ester (), and β-sitosterol () was developed. In most cases, the desired compounds were obtained easily via two-step processes involving esterification reaction employing S-trityl protected thioacetic acid and the corresponding hydoxy-derivative, followed by removal of the trityl-protecting group to obtain the final compounds. The results of our preliminary experiments forced us to change the strategy in the case of genistein (), and the derivatization of diosgenin (), tigogenin (), and capecitabine () resulted in obtaining different compounds from those designed.

The ligand exchange of citrates to thioabiraterone on gold nanoparticles for prostate cancer therapy.

Cancer is one of the leading causes of morbidity and mortality worldwide and nanotechnology has a significant potential to enhance the therapeutic and diagnostic performance of anti-cancer agents. Our work offers a simple and feasible strategy for thiocompound nanomedicines to be used in cancer therapy. Novel gold nanoparticles conjugated with thioabiraterone (AuNP-S-AB) were synthesized and significant new analytical methodologies were developed for their characterization by UV-Vis, TEM, IR, NMR and TGA.

Theoretical modeling of DNA electron hole transport through polypyrimidine sequences: a QM/MM study.

The phenomenon of DNA hole transport (HT) has attracted of scientists for several decades, mainly due to its potential application in molecular electronics. As electron holes mostly localize on purine bases in DNA, the majority of scientific effort has been invested into chemically modifying the structures of adenine and guanine in order to increase their HT-mediating properties. In this work we examine an alternative, never yet explored, way of affecting the HT efficiency by forcing electron holes to localize on pyrimidine bases and move between them.

A diversity of alkylation/acylation products of uracil and its derivatives: synthesis and a structural study.

tert-Butyl dicarbonate (Boc2O) and ethyl iodide (EtI) reactions with uracil (U), thymine (T) and 6-methyluracil (6-MU) were performed following routine procedures in pyridine/DMF solvents and with DMAP as the catalyst. Among 20 synthesized compounds, a derivative of 6-methyluracil substituted by the Boc-pyridine moiety at the C5 position appeared unexpectedly. The NMR spectra confirmed the molecular structure of all uracil derivatives.

Design and Molecular Modeling of Abiraterone-Functionalized Gold Nanoparticles.

The aim of our work was the synthesis and physicochemical characterization of a unique conjugate consisting of gold nanoparticles (AuNPs) and a pharmacologically active anticancer substance abiraterone (AB). The direct coupling of AB with gold constitutes an essential feature of the unique AuNPs⁻AB conjugate that creates a promising platform for applications in nanomedicine. In this work, we present a multidisciplinary, basic study of the obtained AuNPs⁻AB conjugate.

Process-related impurities of eplerenone: determination and characterisation by HPLC methods and Raman spectroscopy.

Two novel high-performance liquid chromatography methods for the determination of process-related impurities of eplerenone drug substance and the designated starting material were developed and validated. Process impurities, including stereoisomers of eplerenone and the intermediate, were controlled using a Kromasil C18 column (250 mm x 4.6 mm; particle size 5 μm), under gradient conditions.

Multinuclear NMR Measurements and DFT Calculations for Capecitabine Tautomeric Form Assignment in a Solution.

The molecular structure of capecitabine (a widely applied prodrug of 5-fluorouracil) was studied by multinuclear NMR measurements and DFT quantum mechanical calculations. One or two tautomeric forms in a solution were detected depending on the solvent used. In the organic solvents, a mixture of two forms of capecitabine was observed: carbamate and imine tautomers.

Pemetrexed conjugated with gold nanoparticles - Synthesis, characterization and a study of noncovalent interactions.

Gold nanoparticles (AuNPs) have been widely used as nanocarriers in drug delivery application. However, the binding mechanism between AuNPs and drug bases still remains a puzzle. Our study included: (i) optimization of three synthesis of the AuNPs-pemetrexed (PE) nanocomposites formation which was monitored by UV-Vis spectroscopy, (ii) identification of PE in gold nanocomposites and mechanism of PE interaction with gold nanoparticles by electrochemistry, NMR and Raman measurements, (iii) characterization of the three nanocomposites by TEM, DSL, ESL, zeta potential, XRPD and TGA analysis.

SYNTHESIS AND ANTIMICROBIAL PROPERTIES OF NEW MANDELATE IONIC LIQUIDS.

Novel mandelate ionic liquids with quartenary ammonium cations were synthesized and characterized. The compounds exhibit antimicrobial activity and the most potent one is of similar efficacy against Gram+ bacteria as its counterpart chloride. On the other hand, the mandelates are much less active against Gram-bacteria and fungi.

Bioequivalence study of 2.5 mg film-coated bisoprolol tablets in healthy volunteers.

Background: Bisoprolol is one of the most widely used beta-blockers characterised by cardioselectivity, and it has no intrinsic sympathomimetic activity. It is commonly used in the treatment of coronary heart disease and heart failure.

Aim: The aim of study was to assess the bioequivalence of the film-coated tablets containing 2.

Cloud-point extraction is compatible with liquid chromatography coupled to electrospray ionization mass spectrometry for the determination of bisoprolol in human plasma.

Cloud-point extraction (CPE) draws increasing interest in a number of analytical fields including bioanalysis, but combining CPE and LC-MS with electrospray ionization (ESI) in the determination of drugs in biological fluids such as plasma, serum or blood has not been reported so far. Bisoprolol was determined in human plasma by CPE using Trition X-114 as a surfactant and metoprolol as the internal standard. NaOH concentration, temperature and Trition X-114 concentration were optimized.

Synthesis, reactivity and biological activity of N(4)-boronated derivatives of 2'-deoxycytidine.

By seeking new stable boron-containing nucleoside derivatives, potential BNCT boron delivery agents, a novel synthetic approach was tested, aimed at a boron attachment via a single bond to an aliphatic carbon of sp(3) hybridization. The latter allowed successful modification of deoxycytidine in the reaction with 2-(iodomethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane of the deoxynucleoside amino group. For new compounds, detailed NMR, LDI HRMS (Laser Desorption/Ionization High-Resolution Mass Spectrometry) analyses along with in vivo phosphorylation studies, toxicity assays and DFT modelling are presented.

17O and 33S nuclear magnetic shielding of sulfur trioxides from the experimental measurements and theoretical calculations.

In a recent (17)O NMR spectra of liquid sulfur trioxide, several unexpected peaks appeared with the temperature-dependent integrated peak ratio. In order to interpret NMR spectra and assign peaks to possible molecular structures, the theoretical quantum mechanical density functional theory and Møller-Plesset second-order perturbation theory calculations were performed. It is suggested that in the liquid sulfur trioxide, apart from monomeric SO3, a significant amount of (SO3)3 cyclic trimers should appear.

Evolutionary Algorithm in the Optimization of a Coarse-Grained Force Field.

Simulations using residue-scale coarse-grained models of biomolecules are less computationally demanding than simulations employing full-atomistic force fields. However, the coarse-grained models are often difficult and tedious to parametrize for certain applications. Therefore, a systematic and objective method to help develop or adapt the coarse-grained models is needed.

Bioequivalence study of 500 mg cefuroxime axetil film-coated tablets in healthy volunteers.

The aim of the study was to investigate the bioavailability of a generic product of 500 mg cefuroxime axetil film-coated tablets (test) as compared to that of a branded product (reference) at the same strength to determine bioequivalence and to apply for regulatory approval. The secondary objective of the study was to evaluate tolerability of both products. A double blinded, randomized, crossover, two-period, single-dose, comparative study was conducted in Caucasian healthy volunteers in fasting conditions.

Bioequivalence and pharmacokinetics of two 10-mg bisoprolol formulations as film-coated tablets in healthy white volunteers: a randomized, crossover, open-label, 2-period, single-dose, fasting study.

Objective: The aim of the study was to investigate the bioavailability of a generic formulation of 10-mg bisoprolol film coated tablets (test) as compared to that of a branded formulation (reference) at the same strength to determine bioequivalence and to apply for regulatory approval. The secondary objective of the study was to evaluate tolerability of both formulations.

Methods: A randomized, crossover, open-label, 2-period, single-dose, comparative study was conducted in healthy white volunteers in fasting conditions.

Tyrosine nitration affects thymidylate synthase properties.

Highly purified preparations of thymidylate synthase, isolated from calf thymus, and L1210 parental and FdUrd-resistant cells, were found to be nitrated, as indicated by a specific reaction with anti-nitro-tyrosine antibodies, suggesting this modification to appear endogenously in normal and tumor tissues. Each human, mouse and Ceanorhabditis elegans recombinant TS preparation, incubated in vitro in the presence of NaHCO(3), NaNO(2) and H(2)O(2) at pH 7.5, underwent tyrosine nitration, leading to a V(max)(app) 2-fold lower following nitration of 1 (with human or C.

Optimization of aripiprazole synthesis.

A series of aripiprazole (AR3) syntheses were performed at laboratory scale (10 mmol of the ARI substrate) in order to optimize the amount of another substrate AR2, as well as Na2CO3, ethanol and varying the reaction time. The reaction parameters were chosen according to the D-optimal plans. A high conversion ratio, about 90-99%, was obtained.