Biomedical subjects

Agnieszka Kaczor

Publications and source records attributed to Agnieszka Kaczor.

6 recordsLinked to original sources

PubMed2006

Methyl 3-methyl-2H-azirine-2-carboxylate photochemistry studied by matrix-isolation FTIR and DFT calculations.

The aliphatic 2H-azirine, methyl 3-methyl-2H-azirine-2-carboxylate (MMAC), has been synthesized and its monomeric form investigated by IR spectroscopy in an argon matrix, at 10 K, as well as theoretically (DFT/B3LYP/6-311++G(d,p)). Two low-energy conformers of MMAC (Ct and Cc) were found in the matrix, both exhibiting the cis conformation around the C-O bond but differing in the arrangement around the C-C(alpha) bond. The two conformers were photoreactive upon in situ broadband UV excitation (lambda > 235 nm), yielding nitrile ylide (P1) and ketene imine (P2) type products, which resulted from cleavage of the C-C or C-N bond, respectively. The kinetics of the reactions leading to the formation of P1 and P2 are of first order, with the processes being favored when the reactant is in the Cc conformation. Very interestingly, the C-N bond photocleavage, which is unusual for aliphatic 2H-azirines, was found to be preferred over the generally favored in 2H-azirines C-C bond breakage. This behavior is attributed to the presence in the molecule of the electron-withdrawing methoxycarbonyl substituent, which accelerates the intersystem crossing toward the T(1) triplet state and, in this way, favors the C-N bond cleavage. In addition to the primary photoprocesses leading to formation of P1 and P2, secondary photoprocesses leading to the decarboxylation and decarbonylation of P2 have been also observed.

Algorithms↗

PubMed2006

Unusual photochemical C-N bond cleavage in the novel methyl 2-chloro-3-methyl-2H-azirine-2-carboxylate.

The structure, preferred conformers, vibrational spectrum, and photochemical behavior of the novel azirine, methyl 2-chloro-3-methyl-2H-azirine-2-carboxylate (MCMAC) were investigated in low-temperature matrixes and in the neat solid amorphous state by infrared spectroscopy and quantum-chemical calculations. Two conformers of the compound were observed in argon, krypton, and xenon matrixes, in agreement with the DFT(B3LYP)/6-311++G(d,p) and MP2/6-311++G(d,p) theoretical calculations. Both conformers were found to exhibit the carboxylic ester group in the cis conformation, differing in the arrangement defined by the O=C-C-Cl dihedral angle (cis and trans, for Ct and Cc forms, respectively). The Ct conformer was found to be the most stable conformer in the gaseous phase as well as in both argon and krypton matrixes, whereas the more polar Cc conformer became the most stable form in the xenon matrix and in the neat solid amorphous phase. In situ broadband UV (lambda > 235 nm) excitation of matrix-isolated MCMAC led to azirine ring C-C and C-N bond cleavages, the latter process corresponding to the most efficient reaction channel. The photochemical cleavage of the C-N bond had never been previously observed in the case of aliphatic 2H-azirines. Two electron withdrawing substituents (methoxycarbonyl group and chlorine atom) are connected to the azirine ring in the novel MCMAC azirine. The simultaneous presence of these two groups accelerates intersystem crossing toward the triplet state where cleavage of the C-N bond takes place. The primary photoproducts resulting from the C-N and C-C ring-opening reactions were also found to undergo further photochemical decarbonylation or decarboxylation reactions.

Argon↗

PubMed2005

Molecular structure of 2-(hydroxyimino)propanohydroxamic acid in solid state and DMSO solution.

The 1H and 13C NMR spectra of 2-(hydroxyimino)propanohydroxamic acid (hpha) were measured in DMSO-d6 solution. The set of several monomeric structures along with the cluster of H-bonded hpha with three DMSO molecules were proposed to fit the experimental data. The calculated chemical shifts [B3LYP/6-311++G(d,p)] strongly suggested the formation of the cluster in which all the labile protons were H-bonded to the solvent molecules. The comparison between experimental and calculated Raman spectra of hpha in DMSO also suggested that in these conditions the investigated compound forms the proposed cluster rather than dimers. According to our calculations [B3LYP/6-31+G(d)] this cluster was energetically stabilized (84-106 kJ mol-1) compared to postulated dimeric structures. On the other hand, formation of dimers was proposed to be present for hpha in solid state. The comparison of the vibrational data (IR, RS) with the computed harmonic frequencies of three most probable dimers [B3LYP/6-31+G(d)] suggested that the dimer in which molecules adopted the zEe-keto form and were linked by two symmetric, almost linear H-bonds between the carbonyl oxygen atoms and the hydroxamic O-H protons was the predominant species of hpha in the solid state. Thus, the structures of hpha in solid state and DMSO solution appeared to be different.

Dimethyl Sulfoxide↗

PubMed2002

Catecholamines and methods for their identification and quantitation in biological tissues and fluids.

Catecholamines act via dopaminergic-, and adrenergic receptors, and are involved in a variety of regulatory systems. They take part in regulation of the response to stress, psychomotor activity, emotional processes, learning, sleep and memory. Due to many catecholaminergic pathways, and a wide range of functions they are involved in, both in the central nervous system and in periphery, a development of the reliable techniques for their extraction and quantitation is essential. This paper presents an overview of the currently applied methodologies for catecholamines detection and identification in various biological samples.

Animals↗

PubMed2002

Non-peptide opioid receptor ligands - recent advances. Part II - antagonists.

This paper is the second part of the review on opioid receptor ligands and deals with the progress in the field of non-peptide opioid receptor antagonists (starting from the pioneering opiate studies in the early seventies) with particular stress on the last decade accomplishments. As X-ray high resolution structure determination of the ligand-receptor systems for G protein-coupled receptors meets with considerable experimental obstacles, the knowledge about ligand interactions with the membrane-bound receptors traditionally derives from structure-activity studies. Hence, such a concise summary, collecting chemically distinct but pharmalogically relative compounds, may be a convenient information source for any research concerning ligand-opioid receptor binding or rational drug design.

Animals↗

PubMed2002

Non-peptide opioid receptor ligands - recent advances. Part I - agonists.

Developments in the domain of non-peptide opioid receptor agonists, beginning from the first evidence of opiate binding to definite receptors, are briefly summarized. The recent achievements are in a more detailed way depicted and discussed. Novel agonists for each of three opioid receptor basic types (delta, kappa and micro) are presented with the special emphasis on one-type-selective ligands. Such selective or even specific agonists have been synthesized with a moderate success. Considerably more serious difficulties concern searching for selective ligands for opioid receptor subtypes (micro(1), micro(2), delta(1), delta(2, kappasub>1), kappasub>2, kappasub>3) which may be connected with the fact that dissimiliarities observed in vivo result from postbinding processes (signaling). For the large number of opioid receptor ligands, their structural diversity and relative easiness of generating them from combinatorial libraries (not comparable even with that of orphanine receptors) it is justified to consider the plasticity of opioid receptors (micro-receptor especially). This remark, in conjunction with the existence of opioid receptor types and subtypes, may enable to create new drugs with significantly reduced side-effects. The above facts and brand new reports about highly-active opioid agonists possessing no moieties thought to be essential for agonist activity make the need of reevaluation of classical opioid receptor pharmacophore model extremely important. In general, research results suggest that selective agonists of opioid receptors can be found both in morphine type of ligands and new structures like pyrido-acridine derivatives (COMP1) or diphenylmethylpiperazine derivatives (SNC 80). Better understanding of the structural prerequisites of the opioid receptors binding domains will certainly lead to even more potent and more selective ligands in a near future.

Animals↗