Binding motifs of cisplatin interaction with simple biomolecules and aminoacid targets probed by IR ion spectroscopy

The primary intermediates resulting from the interaction of cisplatin, cis-(PtCl2(NH3)2], most widespread antitumor drug, with biomolecular targets are characterized. Electrospray ionization is used to deliver ions formed in solution into the gas phase where they are structurally interrogated by vibrational “action” spectroscopy in conjunction with quantum chemical calculations. The aquation products, cis-[PtX(NH3)2(H2O)]+ (X = Cl, OH), lying along the path responsible for biological activity, are shown to display distinctive features responding to ligation pattern and optimized geometry. The IR spectra of trans-[PtX(NH3)2(H2O)]+ are different, testifying that cis and trans complexes are stable, non interconverting species both in solution and in the gas phase. Ligand substitution by simple nucleophiles (L = pyridine, 4(5)-methylimidazole, thioanisole, trimethylphosphate, acetamide, dimethylacetamide, urea and thiourea) yields cis-[PtCl(NH3)2(L)]+ complexes displaying remarkable regioselectivity whenever L presents multiple candidate platination sites. The incipient formation of cisplatin-derived complexes with the recognized biological amino acid targets L-histidine (His) and L-methionine (Met) has been investigated revealing the primary platination event to be mainly directed at the Nπ atom of the imidazole side chain of His and to the thiomethyl sulfur of Met. The isomer and conformer population of the ensuing cis-[PtCl(NH3)2(Met/His)]+ complexes, sampled in the gas phase, can be ascertained by photofragmentation kinetics on isomer/conformer specific resonances.

Effects of Ultrasonic Vibrations Given to an Electrode on the EDM Performance in Processing PCD

EDM machinability of PCD was investigated using a copper electrode giving ultrasonic vibrations. In this series of EDM experiments, three types of ultrasonic vibration modes were selected (axial vibration, flexural vibration and complex vibration). From the experimental results, it was found that EDM efficiency became 3 times higher than the ordinary EDM (no vibration given to the electrode) under the two specific vibration modes, namely, 1) the axial vibration (large) mode and 2) the complex vibration (axial vibration: large + flexural vibration: small) mode. Furthermore, it was shown that the effects resulted from not only the cavitation effect of the working fluid but also the vibrational action of the electrode itself.