Marina Cotta Ramusino

Physico-chemical characterisation of the modifications I and II of (R,S) propranolol hydrochloride: solubility and dissolution studies

The crystallisation conditions and the physicochemical properties of the modifications I and II of (R,S) propranolol hydrochloride were investigated. Detailed methods of preparation of the two forms were described. Data from FTIR spectroscopy, X-ray powder diffraction, thermal analysis, solubility and dissolution studies were used for the identification and the characterisation of the two forms. The forms I and II were easily differentiated by their IR spectra, X-ray patterns and thermal behaviour. The two polymorphs were found to be enantiotropically related to each other. Their stability was followed at room temperature over a period of 1 year and under different conditions of temperature, grinding and compression to verify the tendency to solid solid transition and to study the existence range of the two forms. The equilibrium solubilities of the two polymorphs in n-octanol were determined as well as their dissolution profiles as pellets in aqueous medium. These studies showed that form I, the less thermodynamically stable, was more soluble (by more than 34%) and dissolved faster than form II in agreement with the thermodynamic rules (A. Burger, R. Ramberger, Mikrochim. Acta II (1979) 259-271).

Solid-state investigation of fluocinolone acetonide

Three crystalline modifications of fluocinolone acetonide, A, B and C, were characterized by means of FTIR, DSC, TG-FTIR, MICRO-FTIR and X-ray diffractometry. They were easily differentiated by their IR absorption bands in the 3600-3400 cm-1 range. The thermal behavior was also elucidated using combined techniques; thermomicroscopy and thermogravimetry coupled with Fourier transform infrared spectroscopy were found to be very useful tools for a better understanding of thermal events. On heating, form A and C were fully converted into form B. Polymorph A was found to be enantiotropically related to B, while form C was monotropically related to B. The existence of three polymorphs was confirmed by means of their different X-ray diffraction patterns. Detailed methods of preparation of the three modifications are also described.

UV spectroscopic study and conformational analysis of domperidone

Abstract The UV absorption spectra of domperidone, 2-(3 H )-benzimidazolone and 5-Cl-2-(3 H )-benzimidazolone in CH 3 CN have been studied both in the absence and in the presence of hard acids. A theoretical analysis of the electronic transitions of 2-(3 H )-benzimidazolone has also been performed by means of quantum-mechanical methods. Molecular mechanics (force field) calculations have been carried out to characterize the conformational space of domperidone. The results show a large number of conformers lying with 3 kcal mol −1 with respect to the lowest energy structure.

SEMIEMPIRICAL CALCULATIONS ON THE INTERACTION BETWEEN DIMETHYLTIN(IV) AND DNA MODEL SYSTEM

Abstract The interaction between a dinucleotide triphosphate duplex (DD), mimicking the DNA molecule, and the dimethyltin(IV) cation is studied by the semiempirical PM3 method. The results show that the interaction can occur involving the tin atom and the electron-donor centres of DD, requiring in some cases the presence of water molecules. In particular, the binding of the dimethyltin(IV) moiety with two adjacent phosphate oxygen atoms is allowed by the presence of water molecules coordinating to the tin atom. In this case the tin environment shows a geometry in agreement with 119 Sn Mossbauer and X-ray data.

A 1H NMR study of inclusion complex formation between β-cyclodextrin and monohydroxypyridines

Abstract The inclusion complexes of 2-, 3-, and 4-hydroxypyridines with β-cyclodextrin in aqueous solution have been studied by high field 1 H NMR. All complexes showed a 1:1 stoichiometry and the apparent association constants reflected the polarity of the guest compounds in a qualitative fashion. The inclusion process has been shown to markedly affect the tautomeric equilibrium between the lactim and lactam forms of 3-hydroxypyridine with a preferential inclusion of the former, less polar tautomer.

Conformational properties of o-alkoxy-benzamides in different solvents

Abstract Electronic absorption/emission, 1 H NMR spectroscopy and quantum mechanical calculations have been used to characterize the ground-state conformation of o-methoxy-and o-hexyloxy-benzamides in different solvents. Experimental evidence supports the assumption that a conformation having an intramolecular H-bond between one amide hydrogen and the o-alkoxy oxygen is significantly populated even in aqueous solutions.

Ab initio study of the tautomeric forms of some quinolinediones

Abstract 7,8-dihydroquinoline-4,5 (1 H ,6 H )-dione ( 1 ) and 7,8-dihydroquinoline-2,5-(1 H ,6 H )-dione ( 2 ) in their tautomeric oxo and hydroxy forms have been studied by ab initio Hartree-Fock calculations; tautomerization energies predict a more stable hydroxy structure having an intramolecular hydrogen bond for compound 1, whereas the oxo form is slightly-preferred for compound 2. Fourier Transform-Infra Red (FT-IR) spectra in CHCl 3 solution indicate that the predicted most stable tautomers in the vapour phase remain as such.

Force field study of the interaction between dihydropyridine derivatives and a synthetic Ca2+ channel peptide

Abstract We investigated the binding mode of a set of dihydropyridine calcium channel antagonists to a synthetic Ca 2+ channel peptide with a force field computational procedure. Different conformers of each ligand were docked into the synthetic channel peptide to take into account that the ligand conformation at the receptor site may not correspond to the most stable one of the isolated molecule. In the docking procedure the molecular structure of the Ca 2+ channel was kept rigid while the ligands were assumed to be flexible. The ranking of the computed interaction energies correlated with the biological activity data (expressed as the IC 50 values for the blockage of Ca 2+ induced contraction of K + depolarized rat aorta). The computational procedure also discriminated between the S and R enantiomers of the ligand amlodipine, predicting a stronger interaction of the former with the Ca 2+ channel model.

Theoretical study of carbamic acid [1H-imidazol-2-yl-]methyl ester

Abstract The different tautomers and conformers of carbamic acid [1H-imidazol-2-yl-]methyl ester have been studied by the ab initio MO method at the HF level and the protonation energies of the most stable conformer of each tautomer have been calculated. Some consideration has also been devoted to the characterization of the thermal decomposition processes.