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

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• 作者：Rakesh Kumar^a ; Edward Rosenberg^a ; ^{edward.rosenberg@mso.umt.edu} ; Miriam Inbar Feske^b ; Antonio G. DiPasquale^c
• 关键词：Platinum complexes ; DNA ; TEM ; dGMP ; Osmium clusters
• 出版年：2013
• 出版时间：15 June, 2013
• 年：2013
• 卷：734
• 期：Complete
• 页码：53-60
• 全文大小：1090 K

文摘

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 RC₈H₉NO₂ (benzo[d][1,3]dioxol-5-ylmethanamine) (g class=""boldFont"">1g>), C₈H₁₁N (phenethylamine) (g class=""boldFont"">2g>), C₇H₉N (benzylamine) (g class=""boldFont"">3g>), C₆H₇N (aniline) (g class=""boldFont"">4g>), C₆H₆IN (p-iodo-aniline) (g class=""boldFont"">5g>) C₃H₉NO (2-methoxy-ethylamine) (g class=""boldFont"">6g>) and C₆H₁₃N (cyclohexylamine) (g class=""boldFont"">7g>), were synthesized and their reactions with deoxyguanosine monophosphate (dGMP) were followed by ¹H NMR. Compound g class=""boldFont"">1g> was initially chosen because it showed significant water solubility. Compound g class=""boldFont"">1g> reacted quantitatively but slowly with dGMP and a subsequent Transmission Electron Microscopy (TEM) study of the binding g class=""boldFont"">1g> 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 g class=""boldFont"">1g> with adenine was performed and showed slow and what appeared to be non-specific binding to deoxyadenosine monophosphate (dAMP). The reactions of compounds g class=""boldFont"">2g>-g class=""boldFont"">7g> with dGMP were then studied by ¹H NMR and it was found that g class=""boldFont"">2g> reacted much faster than g class=""boldFont"">1g> with dGMP while the remaining complexes reacted more slowly. No reaction of g class=""boldFont"">2g> 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 g class=""boldFont"">1g> to DNA the synthesis of the complex [Os₃(CO)₁₁PPh₂(CH₂)₂NH₂(en)PtCl]NO₃ (g class=""boldFont"">9g>) 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 ¦Ç² chelate complex Os₃(CO)₁₀PPh₂(CH₂)₂NH₂ (g class=""boldFont"">8g>). Complex g class=""boldFont"">8g> was reacted with [Pt(en)Cl(DMF)]NO₃ in a CO atmosphere to give g class=""boldFont"">9g>. 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 g class=""boldFont"">8g> is also reported.