Relative rates of reaction of Pt(en)Cl (NH2R)+ with guanosine monophosphate as a function of amino group substituent: Toward efficient labeling of DNA for TEM imaging

In an attempt to understand the factors that govern the rates of reaction of the complexes [Pt(en)Cl(NH2R)]+NO3− (en = ethylene diamine) with guanosine monophosphate (dGMP) a series of amine complexes, where Rdouble bond; length as m-dashC8H9NO2 (benzo[d][1,3]dioxol-5-ylmethanamine) (1), C8H11N (phenethylamine) (2), C7H9N (benzylamine) (3), C6H7N (aniline) (4), C6H6IN (p-iodo-aniline) (5) C3H9NO (2-methoxy-ethylamine) (6) and C6H13N (cyclohexylamine) (7), were synthesized and their reactions with deoxyguanosine monophosphate (dGMP) were followed by 1H NMR. Compound 1 was initially chosen because it showed significant water solubility. Compound 1 reacted quantitatively but slowly with dGMP and a subsequent Transmission Electron Microscopy (TEM) study of the binding 1 to a GATC DNA repeat gave a TEM micrograph that showed selective labeling of DNA at guanine, using a technique that allowed the laying down of a straight single strand of DNA on a carbon platform. The TEM suggested a possible side reaction with adenine and so a study of the reaction of 1 with adenine was performed and showed slow and what appeared to be non-specific binding to deoxyadenosine monophosphate (dAMP). The reactions of compounds 2–7 with dGMP were then studied by 1H NMR and it was found that 2 reacted much faster than 1 with dGMP while the remaining complexes reacted more slowly. No reaction of 2 with dAMP was observed in the same time frame. The ultimate goal of the project was to bind a third row transition metal cluster to guanine and given the effective binding of 1 to DNA the synthesis of the complex [Os3(CO)11PPh2(CH2)2NH2(en)PtCl]NO3 (9) is also reported that contains Pt as a linker to label guanine. The synthesis was performed by reacting Os3(CO)10(CH3CN)2 with Ph2PCH2CH2NH2 which gave an η2 chelate complex Os3(CO)10PPh2(CH2)2NH2 (8). Complex 8 was reacted with [Pt(en)Cl(DMF)]NO3 in a CO atmosphere to give 9. 1H and 195Pt NMR indicate formation of an adduct with dGMP but too slowly to be of use in labeling DNA. The solid-state structure of 8 is also reported.