Metal-Modified Base Pairs Involving Different Donor Sites of Purine Nucleobases: trans-[a₂Pt(7,9-DimeG-N1)(9-EtGH-N7)]²⁺andtrans-[a₂Pt(7,9-DimeG-N1)(9-EtG-N7)]⁺(a = NH₃or CH₃NH₂; 9-EtGH = 9-Ethylguanine; 7,9-DimeG = 7,9-Dimethylguanine). Possible Relevance to Metalated DNA Triplex Structures

Abstract

The X-ray crystal structures of four mixed-nucleobase complexes 1a, 1b, 2, and 4 of trans-a2PtII (a = NH3 or CH3NH2) with N1-bonded 7,9-dimethylguanine (7,9-DimeG) and N7-bonded 9-ethylguanine (9-EtGH) are reported. The compounds are discussed in terms of their possible model character for platinated nucleobase triplets of the pu × pu·pym (pu = purine, pym = pyrimidine) type and are compared with known guanine·guanine pairs. Structural differences resulting from a “metal modification” have been studied, as have been stacking and H bonding motifs. 1a and 1b are two modifications of the same compound, trans-[(NH3)2Pt(7,9-DimeG)(9-EtGH)](ClO4)2·H2O. X-ray data for 1a: orthorhombic, Pca21, a = 13.833(3) Å, b = 14.357(3) Å, c = 13.293(3) Å, Z = 4, R = 0.027. 1b: monoclinic, P21/n, a = 13.987(3) Å, b = 12.582(3) Å, c = 15.613(3) Å, β = 104.61(3)°, Z = 4, R = 0.034. trans-[(CH3NH2)2Pt(7,9-DimeG)(9-EtGH)](ClO4)2 (2): orthorhombic, Pca21, a = 13.886(1) Å, b = 14.698(1) Å, c = 13.008(3) Å, Z = 4, R = 0.034. trans-[a2Pt(7,9-DimeG)(9-EtG)](ClO4)·nH2O (3, a = NH3, n = 2; 4, a = CH3NH2, n = 3). X-ray data for 4: monoclinic, C2/c, a = 23.296(5) Å, b = 10.566(2) Å, c = 22.327(4) Å, β = 93.73(3)°, Z = 8, R = 0.047. The metalated base triplet 2·(1-MeC) (1-MeC = 1-methylcytosine) has been detected in DMSO-d 6 solution through 1H NMR spectroscopy, and an ab initio optimized structure of an analogous platinated base triplet has been obtained.

Effects of N7-methylation, N7-platination, and C8-hydroxylation of guanine on H-bond formation with cytosine: platinum coordination strengthens the Watson-Crick pair

“…The pK a values of 8-O-9-MeGH (pK a = 8.77; via UV measurements) (W. Pfleiderer, unpublished results) and trans-[(MeNH 2 ) 2 Pt(7,9-DimeG-N1)(9-EtGH-N7)] 2+ (2) (pK a = 8.24 0.07) [38] have already been reported. The acidity constants of the N1H position of the other guanine compounds were now determined by pD-dependent 1 H NMR measurements, in order to evaluate whether there is a correlation between pK a and the association constant K GC .…”

“…1-Methylthymine (1-MeT) [34], 9-methyladenine (9-MeA) [35], and 1-methylcytosine (1-MeC) [36] were prepared as described. The syntheses of [(dien)Pt(9-EtGH-N7)](ClO 4 ) 2´H2 O (1) [37] and trans-[(MeNH 2 ) 2 Pt(7,9-DimeG-N1)(9-EtGH-N7)](ClO 4 ) 2 (2) [38] were as reported and trans,trans-[(NH 3 ) 2 Pt(1-MeT-N3)(m-9-MeA-N7,N1)Pt(MeNH 2 ) 2 (9-EtGH-N7)](ClO 4 ) 3 (3) was prepared according to [39] using 1-methyluracil (1-MeU) instead of 1-MeT. All other chemicals (either puriss or pro analysi) were from Merck (Darmstadt, Germany), Fluka (Buchs, Switzerland), or Aldrich (Gillingham, Dorset, UK).…”

PtII Coordination to N1 of 9‐Methylguanine: Why it Facilitates Binding of Additional Metal Ions to the Purine Ring

“…[4a, 17] Unlike with adenine, which has its N1 and N7 sites deprotonated over a wide pH range, the problem with guanine is always that N7 is the kinetically preferred metal-binding site, and that substituting the proton at N1 by a suitable metal ion is inherently difficult. [18,19] By transiently blocking the N7 position and by putting a metal ion to N1 of guanine, this problem was thought to be circumvented, as it would eventually leave N7 free for subsequent metal binding.…”

Metal ion-N7 coordination in a ribozyme branch domain by NMR

“…[4][5][6] In larger RNA structures, the situation is more complex, as aside from metal ion binding, also the binding mode, e.g., inner versus outer sphere, as well as small structural changes affect the proton chemical shifts. Metal ion coordination to bridging phosphate moieties has been probed by thiophosphate modification, [7][8][9][10][11][12] but for the nucleobase residues the situation is more complicated.…”