Multiple metal binding to the 9-methyladenine model nucleobase involving N1, N6, and N7: Discrete di- and trinuclear species with different combinations of monofunctional Pd II and Pt II entities

Several di- and trinuclear metal complexes consisting of the model nucleobase 9-methyladenine (9-MeA) or its mono-deprotonated form (9-MeA -) and monofunctional (dien)Pd II, (dien)Pt II, (NH 3) 3Pt II, or (trpy)Pd II in different combinations have been prepared and/or studied in solution by NMR spectroscopy: [{Pd(dien)} 3(9-MeA-N1,N6,N7)]- Cl 3.5(PF 6) 1.53H 2O (1), [(dien)Pd(N1-9-MeA-N7)Pt(NH 3) 3](ClO 4) 49.33H 2O (2), [(dien)Pt-(N1-9-MeA-N7)Pt(NH 3) 3](ClO 4) 4H 2O (3), and [{(trpy)Pd} 2(N1,N6-9-MeA --N7)Pt(NH 3) 3]- (ClO 4) 53H 2O (4). A migration product of 3, [(dien)Pt(N6-9-MeA- N7)Pt(NH 3) 3] 3+ (3a), has been identified in solution. Unlike Pt-adenine bonds, Pd-adenine bonds are substantially labile, and consequently all Pd-containing complexes discussed here (1, 2, 4) exist in aqueous solution in equilibria of slowly interconverting species, which give rise to individual resonances in the 1H NMR spectra. For example, 1 exists in an equilibrium of five adenine-containing species when dissolved in D 2O, 2 undergoes dissociation to [Pt(NH 3) 3(9-MeA-N7)] 2+ or forms the migration product [(dien)Pd(N6-9-MeA --N7)Pt(NH 3) 3] 3+ (2a), depending on pD, and 4 loses both (trpy)Pd II entities as the pD is increased. In no case is Pd binding to N3 of the adenine ring observed. A comparison of the solid-state structures of the two trinuclear complexes 1 and 4 reveals distinct differences between the Pd atoms bonded to N1 and N6 in that these are substantially out of the nucleobase plane in 1, by ca. 0.6 Ã… and -1.0 Ã…, respectively, whereas they are coplanar with the 9-MeA - plane in 4. These out-of-plane movements of the two (dien)Pd II units in 1 are not accompanied by changes in hybridization states of the N1 and N6 atoms. © 2012 American Chemical Society.This work is supported by the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie, and the TU Dortmund. P.J.S.M. thanks the Spanish Ministerio de Economía y Competitividad for funding through the “Ramón y Cajal” program.Peer Reviewe

Acid-base and metal ion binding properties of 2-thiocytidine in aqueous solution

The thionucleoside 2-thiocytidine (C2S) occurs in nature in transfer RNAs; it receives attention in diverse fields like drug research and nanotechnology. By potentiometric pH titrations we measured the acidity constants of H(C2S)(+) and the stability constants of the M(C2S)(2+) and M(C2S-H)(+) complexes (M2+ = Zn2+ , Cd2+), and we compared these results with those obtained previously for its parent nucleoside, cytidine (Cyd). Replacement of the (C2)=O unit by (C2)=S facilitates the release of the proton from (N3)H+ in H(C2S)(+) (pK (a) = 3.44) somewhat, compared with H(Cyd)(+) (pK (a) = 4.24). This moderate effect of about 0.8 pK units contrasts with the strong acidification of about 4 pK units of the (C4)NH2 group in C2S (pK (a) = 12.65) compared with Cyd (pK (a) approximate to 16.7); the reason for this result is that the amino-thione tautomer, which dominates for the neutral C2S molecule, is transformed upon deprotonation into the imino-thioate form with the negative charge largely located on the sulfur. In the M(C2S)(2+) complexes the (C2)S group is the primary binding site rather than N3 as is the case in the M(Cyd)(2+) complexes, though owing to chelate formation N3 is to some extent still involved in metal ion binding. Similarly, in the Zn(C2S-H)(+) and Cd(C2S-H)(+) complexes the main metal ion binding site is the (C2)S- unit (formation degree above 99.99 chelate formation with N3 must be surmised for the M(C2S-H)(+) species in accord with previous solid-state studies of related ligands. Upon metal ion binding, the deprotonation of the (C4)NH2 group (pK(a) = 12.65) is dramatically acidified (pK (a) approximate to 3), confirming the very high stability of the M(C2S-H)(+) complexes. To conclude, the hydrogen-bonding and metal ion complex forming capabilities of C2S differ strongly from those of its parent Cyd; this must have consequences for the properties of those RNAs which contain this thionucleoside