Ewa Matczak-Jon

Interactions of zinc(II), magnesium(II) and calcium(II) with aminomethane-1,1-diphosphonic acids in aqueous solutions

Abstract Complex formation equilibria of the aminomethane-1,1-diphosphonic acids with Zn II , Mg II and Ca II have been studied by potentiometric pH titrations and by means of NMR spectroscopy. The ligands exhibit a strong tendency to form protonated species over a wide range of pH. The most efficient binding mode in all the studied systems is the formation of the six-membered chelate ring involving oxygens of both phosphonate groups. An evident preference for the formation of multinuclear complexes is noted in the case of zinc(II). Magnesium demonstrates preference for mononuclear complexes, whereas calcium(II) tends to form insoluble species with most of the studied ligands. The structures of the main complex species are discussed with respect to the priorities in the hydrogen-bond network organization in solid state.

Proton and carbon-13 NMR studies on coordination of ATP nucleotide to Pd(II)glycyl-L-histidine complex

Abstract The coordination sites and conformation tn Pd(II)- Gly-His complex were examined by the i H and 13 C NMR methods. The coordination equilibria in aqueous solutions containing the Pd(II) Gly-His and ATP in various molar ratios were investigated. The essential influence of the purine ring on the chemical shifts of the H-2 imidazole proton of histidine residue has been found what allowed to conclude about the ternary complex conformation. The presence of the aromatic ring in the plane of the Pd(II) complex was found to affect the competitive. nest in the complex coordination to the purine nitrogens NI and N7. The results of the magnetic resonance studies have been supported by absorption spectroscopy data

Cocrystals of fisetin, luteolin and genistein with pyridinecarboxamide coformers: crystal structures, analysis of intermolecular interactions, spectral and thermal characterization

Fisetin, luteolin and genistein, natural polyphenolic compounds of pharmaceutical interest, were combined with nicotinamide and isonicotinamide with an aim to obtain their cocrystals. A screening experiment utilizing solvent-drop grinding was conducted for those combinations. Cocrystalline phases were identified by XRPD and, as far as possible, obtained as single crystals in solution evaporation approach. Five new cocrystals were isolated, characterized by X-ray single-crystal diffraction, FT-Raman spectroscopy, thermal analysis (DSC and TG–DTA), 1H NMR in solution and compared in terms of supramolecular motifs. Reported herein fisetin–nicotinamide (1 : 2) ethanol hemisolvate (FisNam), fisetin–isonicotinamide (1 : 1) (FisInam), two polymorphic forms of luteolin–isonicotinamide (1 : 1) (LutInam, LutInam2) and genistein–nicotinamide (1 : 1) monohydrate (GenNam) cocrystals reveal the presence of an O–H⋯Narom heterosynthon between an O7 hydroxyl moiety of a flavonoid and the pyridyl ring of a coformer. Within those species, mutual orientations of molecules as well as flavonoid–coformer stoichiometry and solvent presence in crystal lattice are factors that imply resulting motif formation and crystal packing.

A 1:1 cocrystal of baicalein with nicotinamide.

Cocrystallization of baicalein with nicotinamide yields a 1:1 cocrystal [systematic name: pyridine-3-carboxamide-5,6,7-trihydroxy-2-phenyl-4H-chromen-4-one (1/1)], C(6)H(6)N(2)O·C(15)H(10)O(5). The asymmetric unit contains one baicalein and one nicotinamide molecule, both in neutral forms. Molecules in the cocrystal form column motifs stabilized by an array of intermolecular hydrogen bonds.

Interaction of Pd(II) glycyl-l-histidine complex with cytidine and GMP. Proton and carbon-13 nmr studies

1H and 13C nmr studies on the Pd(II)Gly-His complex interaction with cytidine and GMP have shown that the nucleoside binds the palladium complex via N3 nitrogen and the nucleotide binds that complex via N7 nitrogen. The analysis of the Cyd or GMP aromatic ring influence on the chemical shift of the H2 proton or the C2 carbon of imidazole ring has supported the earlier suggestions that nucleoside or nucleotide base and Pd(II) complex plane are almost perpendicular to each other. The Pd(II)Gly-His: Cyd or GMP ternary systems are easily decomposed already in weak basic solutions, which may suggest that the polymerization of Pd(II)Gly-His binary species might be the competitive process in the interactions with nucleosides or nucleotides.

Improving solubility of fisetin by cocrystallization

Fisetin, a naturally occurring polyphenolic compound, has a proven record of in vitro demonstrated anti-carcinogenic, anti-inflammatory and antiviral properties, yet similarly to many promising APIs, its in vivo administration is complicated by low aqueous solubility and unfavourable pharmacokinetics. The presented study was focused on obtaining and characterizing cocrystals of fisetin, with the aim of improving its solubility. Solvent-drop grinding experiments, combined with FT-Raman and XRPD, were conducted to identify new cocrystalline phases, which were afterwards isolated as single-crystals and characterized structurally and in terms of thermal stability and solubility. Dissolution studies of pure fisetin and four cocrystals, namely fisetin–isonicotinamide 1 : 1 (FisInam), fisetin–nicotinamide 1 : 2 hemiethanolate (FisNam), fisetin–nicotinamide 1 : 1 (FisNam2) and fisetin–caffeine 1 : 2 (FisCaf), showed that a 2.5-fold increase of fisetin solubility was achieved for FisNam and to a smaller extent for FisCaf and FisInam (ca. 1.8- and 1.5-fold, respectively).

Molecular organization and solution properties of N-substituted aminomethane-1,1-diphosphonic acids

The crystal structures of N-n-pentylaminomethane-1,1-diphosphonic (1), N-pyrrolidinomethane-1,1-diphosphonic (2), N-(3-carboxy-2-pyridyl)aminomethane-1,1-diphosphonic (3a) and N-(5-methyl-2-pyridyl)aminomethane-1,1-diphosphonic (3c) acids are determined and discussed with respect to their packing patterns and solid state organization. The molecular association and the possible aggregate forms in solution, resulting from the supramolecular features of these materials, are considered. The solution UV and NMR studies are focused on the N-2-pyridylaminomethane-1,1-diphosphonic acids 3a–e in order to establish the influence of the structural changes in passing from 3- to 5- or 6-pyridyl substituted aminomethane-1,1-diphosphonic acids on their general complexation properties.

TRANSITION METAL COMPLEXES OF AMINOPHOSPHONIC ACID ANALOGUES OF METHIONINE AND ALANINE IN AQUEOUS SOLUTION

Abstract The stoichiometrics and stability constants of the nickel(II), copper(II) and zinc(II) complexes of l-amino-3-methylthiopropanephosphonic acid (MetP) and 1-amino-ethanephosphonic acid (a-AlaP) have been determined pH-metrically at 25°C at an ionic strength of 0.2 mol dm−3 (KC1). From the stability data and the absorption spectra of the complexes it has been established that simple aminophosphonic acids coordinate to the nickel(II) and copper(II) ions forming chelate complexes in which the metal binding mode is bidentate with the {NH2, PO3 2-} donor set. 31P and 1H NMR measurements showed that MetP and α-AlaP exhibit similar properties in the presence of zinc(II) ions, but the ligand reacts to form a cyclic phosphonoamidate in neutral and slightly alkaline solution in the Zn(II)-α-AlaP system and at slightly acidic conditions in the Zn(II)-MetP system. This difference reveals that the latter ligand at pH > 7 prefers Zn(II) coordination involving all possible (amino, phosphonate and thioether sulfu...

Potentiometric and spectroscopic studies on Cu(II) complexation to aminophosphonic acid, 1-(3-pyridyl)-1-(n-butylamino)-methanephosphonic acid

Abstract The results are reported of a potentiometric and spectroscopic study of the copper(II) complexes of aminophosphonic acid containing a pyridyl side chain. The aminophosphonic acid coordinates similarly to carboxyl amino acids, forming chelate MA and MA 2 species. Stable MAH species with only a phosphonic group coordinated to the metal ion exist at lower pH. The pyridyl side chain was found to be noneffective in the interaction with Cu(II) ion.

A 1:2 cocrystal of genistein with isonicotinamide: crystal structure and Hirshfeld surface analysis.

Genistein, a naturally occurring polyphenolic compound, was combined with isonicotinamide, a pharmaceutically acceptable coformer, to yield a 1:2 cocrystal [systematic name: 5,7-dihydroxy-3-(4-hydroxyphenyl)chromen-4-one-pyridine-4-carboxamide (1/2)], C15H10O5·2C6H6N2O. The molecules in the cocrystalline phase are present in their neutral forms, and assemble a molecular layer by means of hydrogen bonding.