Interaction of cisplatin in activated diaqua-form with His-Met dipeptide is explored using DFT approach with PCM model. First the conformation space of the dipeptide is explored to find the most stable structure (labeled 0683). Several functionals with double-zeta basis set are used for optimization and obtained order of conformers is confirmed by the CCSD(T) single-point calculations. Supermolecular model is used to determine reaction coordinate for the replacement of aqua ligands consequently by N-site of histidine and S-site of methionine and reversely. Despite the monoadduct of Pt-S(Met) is thermodynamically less stable this reaction passes substantially faster (by several orders of magnitude) than coordination of cisplatin to histidine. The consequent chelate formation occurs relatively fast with energy release up to 12 kcal mol-1.

• Keywords
• Anticancer drug, Computational chemistry, Density functional theory, Heavy metal, Thermodynamics,
• MeSH
• Chelating Agents chemistry   MeSH
• Cisplatin chemistry   MeSH
• Dipeptides chemistry   MeSH
• Histidine chemistry   MeSH
• Kinetics MeSH
• Methionine chemistry   MeSH
• Antineoplastic Agents chemistry   MeSH
• Density Functional Theory * MeSH
• Thermodynamics MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Chelating Agents MeSH
• Cisplatin MeSH
• Dipeptides MeSH
• Histidine MeSH
• Methionine MeSH
• Antineoplastic Agents MeSH

Structural properties of plasmid DNA and model lipid membrane treated with newly synthesized platinum(II) complex cis-[PtCl2{P(CH2CH2COOH)3}2] (cis-DTCEP for short) were studied and compared with effects of anticancer drug cisplatin, cis-[Pt(NH3)2Cl2] (cis-DDP for short). Time Correlated Single Photon Counting Fluorescence Correlation Spectroscopy (TCSPC-FCS) was employed to study interactions between those platinum complexes and DNA. The TCSPC-FCS results suggest that bonding of cis-DTCEP derivative to DNA leads to plasmid strain realignment towards much more compact structure than in the case of cis-DDP. Application of both differential scanning calorimetry and infrared spectroscopy to platinum complexes/DPPC showed that cis-DTCEP slightly increases the phospholipid's main phase transition temperature resulting in decreased fluidity of the model membrane. The newly investigated compound-similarly to cis-DDP-interacts mainly with the DPPC head group however not only by the means of electrostatic forces: this compound probably enters into hydrophilic region of the lipid bilayer and forms hydrogen bonds with COO groups of glycerol and PO2- group of DPPC.

• Keywords
• DNA, DPPC bilayer, DSC, IR spectroscopy, Platinum(II) complex, TCSPC-FCS,
• MeSH
• Models, Chemical * MeSH
• DNA chemistry   MeSH
• Membrane Fluidity MeSH
• Spectrometry, Fluorescence MeSH
• Phosphines chemistry   MeSH
• Coordination Complexes chemistry   MeSH
• Lipid Bilayers chemistry   MeSH
• Platinum chemistry   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• DNA MeSH
• Phosphines MeSH
• Coordination Complexes MeSH
• Lipid Bilayers MeSH
• Platinum MeSH