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Ab initio SCF-MO calculations have been carried out for formic, thioformic and dithioformic acids using the 6-31G* basis set. Fully optimized geometries, atomic charges, relative stabilities and harmonic force fields for s-cis and s-trans conformers of these molecules have been determined and the effects of oxygen-by-sulphur substitution analysed. A realistic description of the molecular charge distribution can be reached by introducing a quantum-mechanical correction to the Mulliken atomic charges, derived from the 'charge'-'charge flux'-'overlap' (CCFO) model. Unlike reported theoretical results, the present ab initio calculations yield relative stabilities of the thioformic acid conformers in agreement with experiment [s-cis (thiol) > s-trans(thio1) > s-cis(thione) > s-trans(thione)]. The success of these ab initio calculations should be partially ascribed to the inclusion of polarization functions on all non-hydrogen atoms. Dithiocompounds constitute an ideal res-'*lance Raman (RR) probe for monitoring catalytic events within an enzyme's active site.'-3 The catalylic hydrolysis of substrates containing the RC(=O)O fragment by cysteine proteases (e.g. papain) proceeds through the formation of a thiolacyl enzyme, RC(=O)S-Enz. Using a thion-substituted substrate, it is possible to generate an enzyme-substrate intermediate that contains the chromophore-C(=S)S-, thus differing from the 'natural' intermediate by a single atom substitution Interpretation of the RR spectra of dithioenzyme-substrate intermediates has relied heavily on joint Raman and crystallographic studies on suitable model c o m p~u n d s .~-~ While our understanding of some of these probes has reached a sophisticated level, it is apparent that the assessment of changes in molecular properties produced by oxygenby-sulphur substitutions in molecules containing the-C(=X)Y-, (X,Y = 0 or S) fragment has a major interest to further oiir understanding of the active site data. We have recently initiated a systematic approach to the study of thione-and thiolsubstituted carboxylic acids and esters using ab initio quantum-mechanical calcu'lations.7-' The results obtained for HCSSH using the 3-21G basis set8 were compared with previous data on HCOOH, HC(=O)SH and HC(=S)OH,'* and revealed a remarkable similarity between molecular properties of dithioformic and thiolformic acids. This trend was also observed along the series of the corresponding methyl esters, HCSSCH3 resembling more HC(=O)SCH, than the compounds possessing an oxygen ester at om. 7*9 The importance of rnesomerism in determining the properties of this kind of molecule (fig. 1) is well known, in particular, for their ground conformational state (the s-cis form). We have proposed' that the main effect resulting from C(=O)O-+ C(=O)S or C(=S)O-C (=S)$ substitutions is originated in the poorer conjugating properties of the sulphur 3p orbitals as compared with those of the oxygen 2p orbitals.

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Organometallic-cyclodextrin inclusion compounds were obtained by the treatment of molybdenocene dichloride (Cp 2 MoCl 2 ) with the modified cyclodextrins (CDs) heptakis-2,3,6-tri-O-methyl-b-CD (TRIMEB) and 2-hydroxypropyl-b-CD (HPbCD) in aqueous solution. The products were isolated by liophilisation and characterised in the solid-state by powder XRD, thermogravimetric analysis, Raman and FTIR spectroscopy, and 13 C CP MAS NMR spectroscopy. The results are consistent with inclusion of Cp 2 MoCl 2 , rather than hydrolysis products such as [Cp 2 Mo(H 2 O)X] + (X = Cl, OH) or [Cp 2 Mo(H 2 O) 2 ] 2+ . The pure non-included metallocene Cp 2 MoCl 2 and its inclusion compounds with unmodified b-CD, TRIMEB and HPbCD were screened for their potential antiproliferative and cytotoxic activity, in both human cancer and healthy cell lines. Inclusion in CD was found to enhance the cytotoxic effect of Cp 2 MoCl 2 , with the TRIMEB adduct displaying the highest anti-tumour activity, along with the lowest toxicity towards non-neoplastic cells.

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