Biomedical subjects

M Józan

Publications and source records attributed to M Józan.

At least 19 recordsLinked to original sources

PubMed1996

[Equilibrium solubility of new potential drugs in water, 1-octanol and cyclohexane].

A method was developed for the determinations of the exact value of isotherm solubility equilibrium of organic compounds in various solvents, that can be used as a standard operating procedure, too. It was used for the determination of equilibrium solubility data of twenty two new organic compounds in three solvents: water, 1-octanol and cyclohexane. The data of ten imidazo-quinazolone and twelve pyrido-quinazolone derivatives were compared with their chemical structures moreover within and between the structural and solvents series. It was proved, that these compounds are not ideal solutes, due to a specific interaction with the solvents which is constant for the imidazo-quinazolones, while it is randomly altering at the different pyrido-quinazolones. The octanol/water partitioning data were calculated using octanol and water solubility data, and those were compared with separately, accurately measured data obtained by the traditional shake-flask method. Our data support, that--as it can be found in most of the literature--at compounds which form special interaction with the solvent the partition coefficient cannot be calculated from the solubility data, and reversely the water solubility cannot be estimated using the determined partition coefficient and some correction factors. It was demonstrated, that the calculated partition coefficient can be biased randomly up to and order of magnitude, and in some cases even the tendency of those is false in a series.

1-Octanol↗

PubMed1993

[Correlation between the structures and physicochemical properties of chemotherapeutic fluoroquinolone agents].

The acid-base properties, the lipophilicity and the HPLC behaviour of nine antibacterial fluoroquinolone derivatives were studied to reveal relationship between these physico-chemical parameters and the chemical structure. Basicity of compounds with two proton-binding sites is depicted here in terms of protonation macro- and microconstants. The concentrations of microspecies (cation, zwitterion, neutral and anion) were calculated in the function of pH. The microspeciation of fluoroquinolones were used to derive relationship between the apparent and true octanol/water partition coefficients. An analysis of structure-chromatographic behaviour has been performed utilizing the retention values was determined in a chromatographic system methanol-aqueous phosphate buffer/ODS. Close correlation was found between the lipophilicity and chromatographic behaviour of the tested compounds when pH dependence and the influence of an ionpairing agent were investigated.

Anti-Infective Agents↗

PubMed1990

[Hydrophobic constant values (delta RMO) of functional groups. II. Interpretation of fragment interactions].

The delta RM0(-CH2-) values have been calculated from fragment values of various alkyl groups (methyl, ethyl, n-propyl). On the basis of delta RM0(-CH2-) values it has been established that the value of the so-called "second" methyl group from aromatic ring has slightly differed from that of the so-called third methylene group and the value of methylene functional group is constant independently from positions of substituents and from electronic interactions. The delta RM0 Me values of methyl group--which is directly attached to aromatic ring--have been regarded as the so-called first methylene group from aromatic ring since value of free energy needed for transfer of methyl group as well as the other physico-chemical data (mole volume, parachor) are nearly the same as those of methylene group according to the literature. Fragment values of methyl groups substituted at various positions have been compared to relating delta RM0(-CH2-) value which is free practically from electronic interactions and it has been ascertained that fragment values have been higher as well as lower. In accordance with literature lower delta RM0 Me values have been interpreted with hyperconjugation effect of aromatic system. On the other hand lower methylene fragment values of alkyl substituted compounds at N1 atom have been attributed to sigma conjugation. In literature higher delta RM0 Me values than relating delta RM0(-CH2-) value are known only in case of orto position to another functional group or by a methyl group on a sterically hindered aromatic ring. Results of tests have shown that values of delta RM0 Me can substantially increase with extension of conjugated aromatic system or with simultaneous substitutions of methyl, methylene groups, respectively at certain locations. The authors have assigned that increase to change of solvate cuver which surrounds the molecule. The same has been manifested by methyl fragment values of quinazoline derivates (tetrahydropyrroloquinazoline, hexahydroazepinoquinazoline) of different electronic distributions. On basis of calculations it has been proved that delta RM0 2-Me and delta RM0 6-Me fragment values of monosubstituted pyrido (1,2-a)-pyrimidine (PP) derivatives have significantly differed from delta RM0 Me values of at other positions (3,7,8,9) methyl substituted compounds. Among disubstituted derivatives only delta RM0 7-Me and delta RM0 8-Me values of 2-phenyl- and 3-carbetoxymethyl-PP derivatives have not differed from each other but methyl fragment values of other positions (6,9) have significantly differed from each other and from other fragment values too.(ABSTRACT TRUNCATED AT 400 WORDS)

Chemical Phenomena↗

PubMed1989

[Ion exchange interactions on silica gel layers. II. Halogen salts of compounds containing organic tertiary and quaternary nitrogen].

Primary and secondary ion exchanges--of hydrochloric acid and hydrobromic acid salts of well hydrolyzing organic bases as well as quaternary ammonium bromide which are important drug substance--taking place on silica gel using methanol as mobile phase have been investigated by thin-layer chromatographic and spectrophotometric methods. In case of tertiary ammonium salts (hydrolyzing salts) basis linked to silanate ion and halogen acid have been formed by primary ion exchange. During secondary ion exchange halogen acid has exchanged metal ions linked to silanate ions on the layer. In case of non hydrolyzing salts, the quaternary ammonium bromide salts it could not surely be proved by the applied methods whether primary ion exchange had been followed by secondary ion exchange or only primary ion exchange had occurred.

Amines↗

PubMed1989

[Ion exchange interactions on silica gel layers. III. Salts of organic bases with organic acids. Organic acids and sodium salts].

By thin-layer chromatographic and spectroscopic (UV, IR) methods it has been proved that bass and acid are formed from salts of organic bases with organic acids during primary interaction because of the ion exchange behaviour of the silica gel layer. The organic acids formed have interacted with metals on the layer during secondary ion exchange and they migrate further as salts again. It has also been established that the extent of secondary ion exchange between metal silanate groups and acids depends on pKS values of acids. On the basis of investigations it can be ascertained with great probability that organic acids of pKS greater than 7 do not interact with metal silanate groups of silica gel layer. Sodium salts of organic acids of pKS less than 3 values similarly do not interact on the other hand sodium salts of organic acids of pKS greater than 3 values are able to interact with silanol groups. It has been established by flame atomic emission method that salicylic acid interacts with sodium ion and 86% of it migrates further as sodium salicylate.

Carboxylic Acids↗

PubMed1989

[Hydrophobic constant values (delta RM0) of functional groups. I. Comparative study of delta RM0 values determined in open (TLC) and closed (OPTLC) chromatographic systems].

delta RM0 values of functional groups (methyl, ethyl, n-propyl, methylene, phenyl, benzyl, saturation) of nitrogen bridgehead compounds [PP = pyrido(1,2-a)-pyrimidine, THPP = tetrahydropyrido(1,2-a)-pyrimidine, CTM-PP = 2,3-cyclotrimethylpyrido(1,2-a)-pyrimidine, CTM-THPP = 2,3-cyclotrimethylenetetrahydropyrido(1,2-a)-pyrimidine, CTRM-PP = 2,3-cyclotetramethylenepyrido(1,2-a)-pyrimidine, CTRM-THPP = 2,3-cyclotetramethylene-tetrahydropyrido(1,2-a)-pyrimidine, CTRM-THPP = 2,3-cyclotetramethylene-tetrahydropyrido(1,2-a)-pyrimidine, THPQ = tetrahydropyrroloquinazoline-, HHAQ = hexahydroazepinoquinazoline-derivates have been calculated from difference of retention values measured on RP-di-C1 stationary phase using methanol + water mobile phases of 6 (10 respectively) various compositions and of retention values (RM0) extrapolated to 0% organic phase. Retention data have been determined in normal chambers loaded with change of phase rate because of the vapour space of the developing chamber and in so-called pressurized ultramicro chamber which is free of change of phase rate and that of vapour space, respectively. It has been ascertained that delta RM0 values of same functional groups--that had been measured in the two different chamber systems--have not significantly differ from each other. It has also been established that opposite direction distortions of RM0 values--measured in normal chambers with mobile phases nearing or moving off 0% organic phase--have generally similar effects on delta RM0 values which are free of change of phase rate. Significant investigations were carried out by programs written on TEXAS SR-52 computer and work has always been done in 95% confidence interval.

Bridged-Ring Compounds↗

PubMed1988