Complete resolution of the microscopic protonation equilibria of N-methyl-D-aspartic acid and related compounds.

Protonation equilibria of N-methyl-D-aspartate (NMDA, a specific glutamate receptor agonist) and its derivatives are characterized at the macroscopic and microscopic levels. (1)H NMR-pH and pH-potentiometric titrations were carried out to determine the macroconstants. Microconstants were obtained by appropriate combination of acidity and NMR parameters of the parent compound and its three synthetic derivatives. These derivatives were close models of the NMDA minor microspecies, allowing the calculation of all the 12 microconstants, the 8 microspecies concentrations and 3 site interactivity parameters. Reliability of the microconstants was assessed by three independent test methods. It was found that protonation of the secondary amino site decreases the beta- and alpha-carboxylate basicities almost exactly by one and two orders of magnitude, respectively, whereas protonation of one of the carboxylates lessens the basicity of the other one by a factor of 3. NMR-pH profiles, macro- and microscopic protonation schemes and species-specific distribution diagrams are presented.

[Current problems in the quality controll of pharmaceutical preparations manufactured in pharmacies I. Identification tests]. / Magisztrális gyógyszerkészítmények minoségellenorzésének aktuális kérdései I. Azonossági vizsgálatok.

Quality controll has fundamental importance in drug safety. During the last 15 years the regulatory changes resulted many problems in the quality controll of pharmaceutical preparations manufactured in pharmacys. The issue of Formulae Normales (FoNo VII.) and the 8th Hungarian Pharmacopoeia raises further questions. Our intentions to show the results have been achived in the area of elaborating new analytical prescriptions (identification and assay) which are crucial due to the obsolescence of previously used prescriptions.

In-solution and on-plate light-catalyzed E/Z isomerization of cyclic chalcone analogues. Lipophilicity of E- and Z-2-(X-benzylidene)-1-benzosuberones.

Some cyclic chalcone analogues [E-2-(X-benzylidene)-1-indanones, -tetralones, and -benzosuberones], on-plate UV light-catalyzed formation of new chromatographic spots, can be observed during thin-layer chromatography (TLC). Gas chromatographic (GC) analysis of selected derivatives indicates the formation of one new substance in each case. GC coupled with mass spectrometry and 1H NMR analysis of the samples reveals that the compounds formed are the respective Z-2-(X-benzylidene)-1-indanones, -tetralones, and -benzosuberones. Two-dimensional TLC shows that the E/Z isomerization is a reversible process. By means of the RP-TLC, the logarithm of n-octanol-water partition coefficient (log P) values of E- and Z-isomeric pairs of selected 2-(X-benzylidene)-1-benzosuberones is determined. The Z-isomers are less lipophilic than the E-isomers.

[Synthesis of dicarboxylic acid monoamides]. / Amidcsoport szelektív kialakítása dikarbonsavakban.

The pharmaceutical and biological importance of the amide moiety is briefly surveyed. Relationships between the electron density and chemical reactivity of the amide site are shortly described. Synthetic methods for the selective formation of monoamino-dicarboxylic acid alpha and beta monoamides are summarised. The three major selective synthesis routes for the preparation of monoamides are introduced. The first class of synthetic methods consists of non selective formation of a- and b-esters, followed by their separation on the basis of different solubilities. Amidation of these esters results in the alpha- or beta-amides respectively. The second class of the reactions utilises the orientating capacity of the amino (ammonium) site, producing first various cyclic anhydrides, lactames, lactones, which are then decomposed in hydrolytic, aminolytic, etc. reactions, resulting selectively in the alpha- or beta-amides or esters. Reactants in the third class of the reactions are dicarboxylic acids with carbon-carbon pi-bonds, and ammonia (or alkyl-amine) which form the appropriate compound in addition reactions. Reactivities and selectivities are interpreted in terms of inductive effects, acidity differences and electronic effects of the various protecting groups. Some important analytical properties of monoamino-dicarboxylic acids and their monoamides are compiled.

Lipophilicity of vinpocetine and related compounds characterized by reversed-phase thin-layer chromatography.

A reversed-phase thin-layer chromatographic method was developed and applied to quantitate the lipophilicity of sparingly water-soluble eburnane alkaloids of therapeutic interest. Our method development included calibration, optimization and validation procedures, using also sets of auxiliary compounds. The log P(TLC) values of five relatively hydrophilic eburnanes were verified by stir-flask studies. The alkaloids were found to have lipophilicity values in the 2.9-4.8 log P(TLC) range. Conclusions on structure-lipophilicity relationships were drawn in terms of ring anellation, character and length of side chain, conformational preferences and moiety-solvent interactions, also supported by molecular mechanics studies.