Energetic aspects of diclofenac acid in crystal modifications and in solutions--mechanism of solvation, partitioning and distribution.

Temperature dependency of saturated vapor pressure and heat capacity for the diclofenac acid (Form II) were measured and thermodynamic functions of sublimation calculated (DeltaG(sub)(298) = 49.3 kJ x mol(-1); DeltaH(sub)(298) = 115.6 +/- 1.3 kJ x mol(-1); DeltaS(sub)(298) = 222 +/- 4 J x mol(-1) x K(-1)). Crystal polymorphic Forms I (P2(1)/c) and II (C2/c) of diclofenac acid have been prepared and characterized by X-ray diffraction experiments. The difference between crystal lattice energies of the two forms were obtained by solution calorimetry: DeltaDeltaH(sol)(I --> II) = 1.6 +/- 0.4 kJ x mol(-1). Temperature dependencies of the solubility in buffers with pH 2.0 and 7.4, n-octanol and n-hexane were measured. The thermodynamic functions of solubility, solvation, and transfer processes were deduced. Specific and non-specific solvation terms were distinguished using the transfer from the "inert" n-hexane to the other solvents. The transfer of diclofenac acid molecules from the buffers to n-octanol (partitioning and distribution) is an entropy driven process.

Toxaphene chemistry: separation and characterisation of selected enantiomers of the Polychloropinene mixtures.

The primary goal for the study presented here was the preparation and characterisation of enantiomeric pure chlorobornane standards (Toxaphene). In this context, we partially modeled the procedure for Polychloropinene production in the former USSR. The initial reaction was ionic addition of hydrogen chloride to (1S)-alpha-pinene resulting predominantly in (1S)-2-endo-chlorobornane. Further photochlorination gave mixtures of chlorinated terpenes with different average content of Cl per molecule. The resulting mixtures were separated on a silica-gel column and a number of known hepta to decachlorobornanes were identified in fractions with the help of NMR and GC (using electron capture and mass spectrometric detection)--but in very unusual ratios as compared to the technical Toxaphene mixture formerly produced by Hercules (USA). Also several previously unknown congeners were isolated or detected. Three of the isolated congeners were obtained in crystalline state and X-ray crystallography showed their enantiomeric purity.

Interrelation between thermochemical and structural data of polymorphs exemplified by diflunisal.

Three known and one new unsolvated polymorphic phase A, B, C, and D of diflunisal were grown and studied by X-ray diffraction, IR-spectroscopy, solution calorimetry, and DSC methods. Their structures are compared to another previously described modification E.1 Relationships were studied between O-H and C=O stretching frequencies and between C=O stretching frequency and the molecular volume of diflunisal in the respective crystal lattice. According to regularities found it was proposed that the existence of polymorphic forms is determined by conformational flexibility of the molecule, ability to create inter- and intramolecular hydrogen bonds and the competition between nonspecific van der Waals and specific hydrogen bond interactions. The volume per molecule in the crystal lattice are: A < B < C < E < D (XRD Ito method). Forms A and C are enantiotropic with a difference in crystal lattice energies of 1.9 +/- 0.5 kJ.mol( - 1). Modifications B, C, D, and A, B, D are monotropic. Based on solution enthalpies, absolute values of the lattice showed only small differences ("isoenergetic" polymorphs), and can be arranged in increasing order: B approximately A < C < D.

Thermodynamics of sublimation, crystal lattice energies, and crystal structures of racemates and enantiomers: (+)- and (+/-)-ibuprofen.

Thermodynamic differences between ibuprofen (IBP) racemate and the (+)-enantiomer were studied by X-ray diffraction, thermoanalysis, and crystal energy calculations. The thermodynamic functions of sublimation (as a measure of crystal lattice energy) were obtained by the transpiration method. The sublimation enthalpies (DeltaH(sub)) of (+/-)-IBP and (+)-IBP are 115.8 +/- 0.6 and 107.4 +/- 0.5 kJ. mol(-1), respectively. Using the temperature dependency of the saturated vapor pressure, the relative fractions of enthalpy and entropy of the sublimation process were calculated, and the sublimation process for both the racemate and the enantiomer was found to be enthalpy driven (62%). Two different force fields, Mayo et al. (M) and Gavezzotti (G), were used for comparative analysis of crystal lattice energies. Both force fields revealed that the van der Waals term contributes more to the packing energy in (+)-IBP than in (+/-)-IBP. The hydrogen bonding energy, however, contributes at 29.7 and 32.3% to the total crystal lattice energy in (+)-IBP and (+/-)-IBP (M), respectively. Furthermore, different structure fragments of the IBP molecule were analyzed with respect to their contribution to nonbonded van der Waals interactions. The effect of the C-H distance on the van der Waals term of the crystal lattice energy was also studied.