Metalated Nucleobase Quartets:  Dimerization of a Metal-Modified Guanine, Cytosine Pair oftrans-(NH₃)₂Pt^IIand Formation of CH···N Hydrogen Bonds

Abstract

The X-ray crystal structures of two complexes of the composition trans-[Pt(NH3)2(9-EtG-N7)(1-MeC-N3‘)]X·nH2O (1) with 9-EtG = 9-ethylguaninate and 1-MeC = 1-methylcytosine are reported. 1b (X = picrate, n = 1) crystallizes to produce a dimetalated base quartet, held together by H-bonding interactions between pairs of cations. This feature essentially corresponds to the solution structure previously proposed by us on the basis of 1H NMR and ESI-MS, with a H-bonding interaction between the aromatic H5‘ proton of 1-MeC and the deprotonated N1 position of 9-EtG. 1c (X = trifluoromethanesulfonate, n = 0) crystallizes in a radically different fashion as a consequence of nucleobase rotation about the Pt−N bond, leading to a reversed Hoogsteen arrangement without any intracomplex H bonding between the two bases. In the solid-state structure of 1b short intermolecular H bonds exist between the exocyclic NH2 group of 1-MeC and O6 of 9-EtG (2.715(7) Å). Considerably longer intra- (N4‘(1-MeC)···O6(9-EtG), 3.229(6) Å) and intermolecular (C5‘(1-MeC)···N1(9-EtG), 3.548(7) Å) H bonds are primarily a consequence of considerable base twisting, presumably caused by stacking between the guanine residues and the picrate anions. In DMSO-d 6 solution, the cyclic base quartet structure is favored, regardless of the nature of the anion X (X = picrate, trifluoromethanesulfonate, perchlorate, nitrate). An association constant K D = 44.1 ± 3.2 M-1 for the dimerization has been determined.

Canonical and unconventional pairing schemes between bis(nucleobase) complexes oftrans-a2PtII: Artificial nucleobase quartets and C—H…N bonds

“…4). The behavior of 4 is thus similar to that of trans-[(NH 3 ) 2 Pt(1-MeC-N3)(9-EtG-N7)] ϩ , which has been demonstrated to form a stable base quartet structure both in solution and in the solid state (14). Therefore, we propose that 4 adopts a similar structure and consists of two ϩ1 cations, with pairs of intermolecular hydrogen bonds holding them together (Scheme 3).…”

“…1). H bond lengths vary between 2.99(2) and 3.07(2) Å (two crystallographically independent molecules) and are thus at the lower end of similar H bonds in other examples of Pt II guanine complexes (14,34). Adjacent tapes display partial stacking of the purine rings and are connected by intermolecular H bonds between NH 3 ligands and O6 sites of the guanine ligands (see Figs.…”

“…Among others, it was these observations that prompted the work reported here, which also originated from the more general question of how platinated model nucleobases such as 9-methylguanine (9-MeGH), 9-ethylguanine, 9-methylhypoxanthine (9-MeHxH), and 1-methylcytosine (1-MeC) organize via H bonds in the solid state and in solution. As will be reported, H bond formation between aromatic protons of nucleobases and endocyclic N atoms is observed in several instances, a feature still extremely rare in nucleic acid chemistry (14,21,22 in DMSO-d 6 were calibrated to the signal of partially deuterated solvent. Spectra recorded in dimethylformamide-d 7 were likewise referenced against solvent peaks.…”

“…Because of their shape and charge, these compounds can be expected to have a natural affinity for tetra-stranded DNA in general and telomere sequences in particular. The use of metal ions (M) displaying linear coordination geometries and the fact that purine nucleobases, on simultaneous metal binding to N1 and N7, provide 90°angles between their M-N vectors and hence represent angular building blocks of squares and rectangles have enabled the construction of a variety of artificial M-base quartets (11)(12)(13)(14)(15)(16). Examples are given in Scheme 1.…”

“…The association constant of 4c was determined by concentration-dependent 1 H NMR measurements in DMSO-d 6 as described (14). The triflate salt was used for solubility reasons.…”