Teresa Żołek

13C CP MAS NMR and GIAO-CHF calculations of coumarins

13C cross-polarization magic-angle spinning NMR spectra were recorded for a series of solid coumarins. Ab initio calculations of shielding constants were performed with the use of GIAO-CHF method. The combined CPMAS NMR and theoretical approach was successful in characterizing solid-state conformations of coumarins; a relationship sigma (ppm) = -1.032 xdelta + 205.28 (R(2) = 0.9845) can be used to obtain structural information for coumarins, for which solid-state NMR or crystal structure data are not available.

A computational model for selectivity evaluation of 2-(3,4-dimethoxyphenyl)ethylamine (homoveratrylamine) imprinted polymers towards biogenic compounds

A computational model was proposed to evaluate the affinity and selectivity of 2-(3,4-dimethoxyphenyl)ethylamine (homoveratrylamine) imprinted polymers. Four functional monomers: methacrylic acid, 1-vinylimidazole, 4-vinylpyridine, and allylamine were taken into account. Two dielectric constants were used for solvent simulations: a value of ɛ=2.38r(ij) for toluene was used in the analysis of prepolymerization complexes, and a value of ɛ=36r(ij) for methanol-water was used in the investigations of adsorption. Theoretical analysis predicted the highest affinity for the polymer synthesized from methacrylic acid. Experimental results confirmed the finding. The prepolymerization complex formed by homoveratrylamine and four methacrylic acid molecules was used to design the polymer cavity. The selectivity of the polymer was analyzed as a simulation of adsorption of six compounds in the cavity by docking procedure. Selected compounds are structurally related to the template or can be present in biological samples. The designed polymer has high selectivity towards homoveratrylamine. The proposed computational procedure could be used for successful evaluation of the imprinted polymers.

Separation of octopamine racemate on (R,S)-2-amino-1-phenylethanol imprinted polymer--Experimental and computational studies.

Ten molecularly imprinted polymers coded as MIP1-MIP10 were prepared by the radical bulk polymerization using (R,S)-(±)-2-amino-1-phenylethanol as the structural analog of the target analyte (R,S)-octopamine. The functional monomers, 4-vinylbenzoic acid (1), methacrylic acid (2), acrylic acid (3), trifluoromethacrylic acid (4), itaconic acid (5), acrylamide (6), isopropenylbenzene (7), 2-hydroxyethyl methacrylate (8), 2-(diethylamino)ethyl methacrylate (9), allylamine (10) were polymerized consecutively with the ethylene glycol dimethacrylate cross-linker in methanol as the porogen. On the basis of the binding capacity of (R,S)-octopamine MIP1 with affinity factor equal to 6.37 was selected for further analysis. The affinity of polymer matrix MIP1 was tested by the non-competitive binding experiments of eight structurally related analytes. Finally, molecularly imprinted solid phase extraction (MISPE) of (R,S)-octopamine from spiked human serum albumin was carried out in order to verify the applicability of novel sorbent. The molecular modeling was employed to rationalize the stereodifferentiation of the analytes by the stereospecific sites formed in the polymer matrix.

A separation of tyramine on a 2-(4-methoxyphenyl)ethylamine imprinted polymer: An answer from theoretical and experimental studies

A 2-(4-methoxyphenyl)ethylamine imprinted polymer (MIP) was successfully applied for the selective separation of tyramine. A computational analysis was used to predict the affinity of the polymer matrix towards tyramine and a preliminary experimental evaluation was made for the target analyte. Then the experimental analysis of polymer towards tyramine was continued. The binding sites were characterized with employment of the Langmuir and Freudlich models. After the optimization of solid phase extraction towards tyramine, the most appropriate systems for the extraction steps were chosen: methanol-water 85:15 v/v for the loading and the washing as well as 0.04 M aq. ammonium acetate-methanol 30:70 v/v for the elution steps. The biogenic compounds as tryptamine, serotonin, octopamine, synephrine, and l-tyrosine were used for the selectivity study on the basis of binding capacities of the analytes on the imprinted and the non-imprinted polymers. The theoretical approach to obtained results allowed to explain the adsorption selectivity of the tested polymer. Finally, the complex matrix of bovine serum albumin was used to show the usefulness of imprinted material for bioanalysis. The obtained recoveries showed the superiority of MIP over the commercial sorbent C18. Total recoveries of tyramine from spiked bovine serum albumin sample were determined as: 95±2%, 14±3%, and 1.9±0.4% for the imprinted, non-imprinted, and commercial C18 sorbents, respectively.

1H, 13C MAS NMR and GIAO-CPHF calculations of chloramphenicol, thiamphenicol and their pyrrole analogues

Abstract The 13 C CP MAS and 1 H MAS NMR and ab initio (GIAO-CPHF) calculations were used to obtain structural information on two known antibiotics: chloramphenicol, and thiamphenicol, and two new analogues: dl - threo -1-(1-methyl-4-nitro-pyrrole-2-yl)-2-dichloroacetamidopropane-1,3-diol and dl - threo -1-(1-methylsulfonylpyrrole-3-yl)-2-dichloroacetamidopropane-1,3-diol.

Structural aspects of intermolecular interactions in the solid state of 1,4‐dibenzylpiperazines bearing nitrile or amidine groups

X-ray diffraction analyses for new pentamidine analogs are presented: 1,4-bis(4-cyanobenzyl)piperazine (1) crystallizes in the triclinic space group () and 1,4-bis(4-amidinobenzyl)piperazine tetrahydrochloride tetrahydrate (2) in the monoclinic space group (P21/n) revealing a complex system of hydrogen bonds for (2).

Drug likeness prediction of 5-hydroxy-substituted coumarins with high affinity to 5-HT 1A and 5-HT 2A receptors

Abstract One of the latest trends is search for the new anti‐psychotic drugs among coumarin derivatives with piperazine moiety. Their therapeutic potential can be hampered by poor physico‐chemical parameters as low brain penetration or limited transport in the body fluid. Herein, we predicted the drug likeness of six coumarins with high affinity towards 5‐HT1A and 5‐HT2A receptors. Subsequent experimental determination of their binding constants to human serum albumin (HSA) revealed the binding with a moderate strength (logK = 4.8–5.8) at the Sudlows site 1, which represents a possibility of temporary storage of tested coumarins on HSA. Computational mapping of the binding of coumarins ‐ HSA complexes showed that the coumarin rings of all tested compounds were similarly located within the hydrophobic binding pocket of HSA, while the rest of molecules (composed with alkyl chains, piperazine and benzene rings) decided about the difference in binding modes by the hydrogen bonding interactions. The proton dissociation constants (pKa) of the compounds were also determined by UV–vis spectrophotometric titrations to obtain the distribution of the species in the different protonation states at physiological pH of 7.4. A good agreement of the computationally‐determined free enthalpy values of the ligand – HSA complexes with the values determined by experimental fluorescence quenching data could be a promising prospect for proposed theoretical strategy. Graphical abstract Figure. No caption available.

Theoretical evaluation of ADMET properties for coumarin derivatives as compounds with therapeutic potential

&NA; Coumarins have received a considerable attention in the last three decades as the lead structures for the discovery of orally administrated chemotherapeutics. Despite of the large amounts of in vitro activity information, relatively a little is known about their bioavailability in vivo. This paper presents an evaluation of drug‐likeness of 31 coumarin derivatives on the basis of Lipinskis rule of five, and computed ADMET parameters (adsorption, distribution, metabolism, elimination and toxicity). Nine compounds which were predicted as showing the cardiotoxicity, were examined as hERG K+ channel blockers using in silico approach. Additionally, an impact of the acetyl group at benzene ring on pharmacokinetic profile was scrutinized for the tested coumarin derivatives. None of the analyzed coumarins violated the Lipinskis rule of five for orally administered drugs, and all tested compounds will remain in the qualitative likelihood of crossing the blood‐brain barrier. 7‐O‐Alkilaminocoumarins showed no hepatotoxicity, but introduction of the nitrile or the amidine groups increased the levels of the hepatoxicity markers. Computed parameters of toxicity revealed cardiotoxic potency of twenty‐five tested compounds. The proposed hERG K+ channel binding simulations helped in the understanding the molecular basis of coumarins cardiotoxicity. The presented theoretical studies explained some aspects of coumarin pharmacokinetics and identified the positive effect of the acetoxy substituent on the tested parameters. Graphical abstract Figure. No caption available.