Connectivity patterns and rotamer states of nucleobases determine acid–base properties of metalated purine quartets

• Published in: Journal of inorganic biochemistry Vol. 148; pp. 93 - 104
• Main Authors: Lüth, Marc Sven, Freisinger, Eva, Kampf, Gunnar, Garijo Anorbe, Marta, Griesser, Rolf, Operschall, Bert P., Sigel, Helmut, Lippert, Bernhard
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2015
• Subjects: Acidity constants; Acids - chemistry; Adenine; Adenine - chemistry; Alkalies - chemistry; Amines - chemistry; Coordination Complexes - chemistry; Crystallography, X-Ray; Hydrogen-Ion Concentration; Kinetics; Ligands; Linkage isomers; Magnetic Resonance Spectroscopy; Metals - chemistry; Models, Chemical; Molecular Structure; Nitrogen - chemistry; Organoplatinum Compounds - chemistry; Platinum; Platinum - chemistry; Potentiometry; Purines - chemistry; Quartet formation; Quartet formation; Adenine; Acidity constants; Platinum; Linkage isomers
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2015.02.004

Potentiometric pH titrations and pD dependent 1H NMR spectroscopy have been applied to study the acidification of the exocyclic amino group of adenine (A) model nucleobases (N9 position blocked by alkyl groups) when carrying trans-a2PtII (with a=NH3 or CH3NH2) entities both at N1 and N7 positions. As demonstrated, in trinuclear complexes containing central A–Pt–A units, it depends on the connectivity pattern of the adenine bases (N7/N7 or N1/N1) and their rotamer states (head–head or head–tail), how large the acidifying effect is. Specifically, a series of trinuclear complexes with (A-N7)–Pt-(N7-A) and (A-N1)–Pt–(N1-A) cross-linking patterns and terminal 9-alkylguanine ligands (9MeGH, 9EtGH) have been analyzed in this respect, and it is shown that, for example, the 9MeA ligands in trans-,trans-,trans-[Pt(NH3)2(N7-9MeA-N1)2{Pt(NH3)2(9EtGH-N7)}2](ClO4)6·6H2O (4a) and trans-,trans-,trans-[Pt(NH3)2(N7-9EtA-N1)2{Pt(CH3NH2)2(9-MeGH-N7)}2](ClO4)6·3H2O (4b) are more acidic, by ca. 1.3units (first pKa), than the linkage isomer trans-,trans-,trans-[Pt(CH3NH2)2(N1-9MeA-N7)2{Pt(NH3)2(9MeGH-N7)}2](NO3)6·6.25H2O (1b). Overall, acidifications in these types of complexes amount to 7–9units, bringing the pKa values of such adenine ligands in the best case close to the physiological pH range. Comparison with pKa values of related trinuclear PtII complexes having different co-ligands at the Pt ions, confirms this picture and supports our earlier proposal that the close proximity of the exocyclic amino groups in a head–head arrangement of (A-N7)–Pt–(N7-A), and the stabilization of the resulting N6H–⋯H2N6 unit, is key to this difference. Linkage isomers of composition X-M-A-M-A-M-X (M=trans-a2PtII, a=am(m)ine; A=9-alkyladenine; X=other nucleobase or NH3/amine) display differences in pKa values of the first A to undergo deprotonation at the exocyclic amino group, depending on the central cross-linking pattern and the rotamer state of the adenines. [Display omitted] •Trinuclear trans-a2PtII complexes with two bridging 9-alkyladenine (A) ligands are reported.•PtII coordination to both N1 and N7 of A causes a large drop in pKa of the N6H2 group.•ΔpKa depends on the cross-linking pattern and the rotamer state of the central As.•Linkage isomers display different pKa values.