Analysis of the vibrational spectra of new OH-containing E-4-arylmethylene-3-isochromanones and 3-arylcoumarins.

A combined experimental and theoretical approach is presented to structural characterization of fairly large, newly synthesized organic molecules in order to enhance the effectiveness of their instrumental analysis by vibrational spectroscopy. The method consists of measurement of FT-IR and Raman spectra of the reaction products and subsequent ab initio or DFT quantum mechanical calculations (prediction) of the vibrational spectra for any anticipated structural varieties of the synthesized molecules. Comparison of the measured and computed frequencies as well as the observed and simulated spectra is performed to resolve any uncertainties in identifying the reaction products. Vibrational frequency and normal mode calculations based on scaled quantum mechanical (SQM) force fields performed at the DFT/B3LYP/6-31G* level of theory are demonstrated to provide a wealth of information that have been used in this work to ascertain the molecular structure, probable conformation and H-bond properties of three new isochromanone or coumarin derivatives, namely: 3-([2'-hydroxymethyl]-phenyl)-coumarin (1), E-4-(3'-hydroxyphenylmethylene)-3-isochromanone (2), and 2-[(2'-hydroxymethyl)phenyl]-3H-naphto[2,1-b]pyran-3-one (3).

Analysis of vibrational spectra of some new E- and Z-4-arylidene-3-isochromanones; Part 2. Isomers and conformers of the 2'-pyrrolyl and 2'-nitrophenyl derivatives.

The infrared and Raman spectra of resolved E and Z isomers of some 4-arylidene-3-isochromanone derivatives were analyzed with the aim of pointing out the differences in vibrational behavior of their coexisting stable conformers. Quantum mechanical (QM) density functional (DFT/B3LYP/6-31*) and normal coordinate calculations were carried out to establish the equilibrium structures and to facilitate the interpretation of the vibrational spectra of the 2'-pyrrolyl and 2'-nitrophenyl derivatives. The frequencies and intensities calculated according to the scaled quantum mechanical (SQM) force field method were used to simulate the IR and Raman spectra and compare them to the measured ones. The results demonstrate that the adopted methodology is capable of treating these fairly large polycyclic molecules. The resulting spectral simulations and detailed vibrational description can be highly useful in clarifying spectral differences brought about by cis-trans isomerism and indicating the extent of spectral changes due to further conformational changes of the aryl substituent attached to the olefinic C=C bond.

Biotransformation of deramciclane in primary hepatocytes of rat, mouse, rabbit, dog, and human.

The metabolic fate of deramciclane [(1R,2S,4R)-(-)-2-phenyl-2-(2'-dimethylamino-ethoxy)-1,7,7-trimethyl-bicyclo[2.2.1]heptane], a new anxiolytic drug candidate, has been determined in rat, mouse, rabbit, dog, and human hepatocytes. Rat and rabbit cells were the most active, whereas the rate of metabolism was quite slow in human hepatocytes. During biotransformation, deramciclane underwent side chain modification and oxidation at several positions of the molecule. The side chain modification led to the formation of N-desmethyl deramciclane and phenylborneol. The oxidation of deramciclane resulted in several hydroxy-, carboxy-, and N-oxide derivatives. The hydroxylation took place at primary or secondary carbons of the camphor ring as well as at the side chain; furthermore, dihydroxylated derivatives were also found. The side chain-modified metabolites were also oxidized to hydroxy- or carboxy-derivatives. Conjugation of phase I metabolites, as a route of elimination, was also observed in rat, rabbit, and dog hepatocytes. Although there were some species differences in biotransformation of deramciclane, it was concluded that phase I metabolism in human liver cells seemed to be similar to the metabolism in the hepatocytes isolated from rat. With careful approach, the rat model may be considered to be predictive for human metabolism of deramciclane.

N-benzoylimido complexes of palladium. Synthesis, structural characterisation and structure-reactivity relationship.

Benzoyl azides, ArC(O)N3, 2, (Ar = phenyl or substituted phenyl), react with [Pd2Cl2(dppm)2], 1, [dppm = bis(diphenylphosphino)methane] with the formation of novel [Pd2Cl2(mu-NC(O)Ar)(dppm)2], 3, benzoylnitrene complexes that were structurally characterised by multinuclear magnetic resonance and IR spectroscopy and, in several instances, by single crystal X-ray diffraction. As shown by crystallographic studies, the C2P4Pd2 rings adopt extended twist-boat conformations with methylene groups bending towards the bridging benzoylimido moieties. X-ray diffraction studies have revealed the chiral nature of the imido complexes, the chiral element being the propeller-like C2P4Pd2 ring. Structural data accumulated on complexes 3 such as short C-N distances (1.32 A), elongated C=O bonds (1.30 A) as well as the outstandingly high barrier to internal rotation around the N-C(O) linkage (88.3 kJ mol(-1)) are in line with extensive ppi-ppi interaction between the bridging nitrogen and the carbonyl carbon atoms. Theoretical calculations indicate an electron shift from the dimer towards the apical nitrogen atom, which, in turn, facilitates the donation of electrons towards the carbonyl moiety. To elucidate the structure-reactivity relationship of benzoyl azides towards 1, crystallographic and solution IR spectroscopic studies were carried out on a series of para-substituted benzoyl azides. The reaction obeys the Hammett equation. The large positive value of the reaction constant indicates that the azides act as electrophiles in the reaction studied. The enhanced reactivity of 2-nitrobenzoyl azide has been attributed to a decreased conjugation of the phenyl and carbonyl moieties in this reagent.