The cyclometalated platinum(II) complex [Pt(L)Cl], where HL is a new cyclometalating ligand 2-phenyl-6-(1H-pyrazol-3-yl)pyridine containing C(phenyl), N(pyridyl), and N(pyrazolyl) donor moieties, was found to possess two-photon-induced luminescent properties. The two-photon-absorption cross section of the complex in N,N-dimethylformamide at room temperature was measured to be 20.8 GM. Upon two-photon excitation at 730 nm from a Ti:sapphire laser, bright-green emission was observed. Besides its two-photon-induced luminescent properties, [Pt(L)Cl] was able to be rapidly accumulated in live HeLa and NIH3T3 cells. The two-photon-induced luminescence of the complex was retained after live cell internalization and can be observed by two-photon confocal microscopy. Its bioaccumulation properties enabled time-lapse imaging of the internalization process of the dye into living cells. Cytotoxicity of [Pt(L)Cl] to both tested cell lines was low, according to MTT assays, even at loadings as high as 20 times the dose concentration for imaging for 6 h.

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The hydrolysis process of Ru (III) complex (HL)[trans- RuCl 4L(dmso-S)] (L=4-amino-1,2,4-triazole) (1), a potential antitumor complex similar to the well-known antitumor agent (ImH)[trans- RuCl 4(dmso-S)(Im)](NAMI-A), was investigated using density functional theory (DFT) with the conductor-like polarizable continuum model (CPCM). The structural characteristics and the detailed energy profiles for the hydrolysis processes of this complex were obtained. For the first hydrolysis step, complex 1 with 4-amino-1,2,4-triazole ligand shows much faster aquation than NAMI-A with imidazole ligand and complex 2 with 4H-1,2,4-triazole ligand, and such a calculated result is in good agreement with the experimental one. For the second hydrolysis step, the formation of cis-diaqua products is found to be thermodynamically preferred over the trans isomers. In addition, on the basis of the analysis of electronic characteristics of species in the hydrolysis process, the trend in abilities (A) of hydrolysis products attacked nucleophilicly by pertinent biomolecules is revealed. These theoretical results will help in understanding the action mechanism of this potential Ru (III) drug with pertinent biomolecular targets.

A theoretical study on the binding conformations and the quantitative structure-activity relationship (QSAR) of combretastatin A4 (CA-4) analogs as inhibitors toward tubulin has been carried out using docking analysis and comparative molecular field analysis (CoMFA). The appropriate binding orientations and conformations of these compounds interacting with tubulin were revealed by the docking study; and a 3D-QSAR model showing significant statistical quality and satisfactory predictive ability was established, in which the correlation coefficient (R(2)) and cross-validation coefficient (q(2)) were 0.955 and 0.66, respectively. The same model was further applied to predict the pIC(50) values for 16 congeneric compounds as external test set, and the predictive correlation coefficient R(2)(pred) reached 0.883. Other tests on additional validations further confirmed the satisfactory predictive power of the model. In this work, it was very interesting to find that the 3D topology structure of the active site of tubulin from the docking analysis was in good agreement with the 3D-QSAR model from CoMFA for this series of compounds. Some key structural factors of the compounds responsible for cytotoxicity were reasonably presented. These theoretical results can offer useful references for understanding the action mechanism and directing the molecular design of this kind of inhibitor with improved activity.