METAL-MODIFIED NUCLEOBASE PAIRS - MIXED ADENINE, THYMINE COMPLEXES OFTRANS-A(2)PT(II) (A = NH3, CH3NH2) WITH WATSON-CRICK AND HOOGSTEEN ORIENTATIONS OF THE BASES

Replacement of a weakly acidic N-H proton of a H bond between two nucl eobases (neutral or hemiprotonated) by a metal species of suitable geo metry generates metal-modified nucleobase pairs. Depending upon the co mbination of bases and/or respective donor sites involved in metal bin ding, these adducts can be divided in metal analogues of (i) homopyrim idine and homopurine pairs, (ii) Watson-Crick pairs, (iii) Hoogsteen p airs, (iv) pairs between noncomplementary bases, and (v) non-nucleobas e, nucleobase pairs. Representative examples of (ii)-(v) have been pre pared and are reported. In three cases, (ii), (iii), and (v), X-ray cr ystallography has been used to determine structural details. -[(CH3NH2 )2Pt(1-MeT-N3)(9-MeA-N1)]ClO4.3.25H2O(4') crystallizes in the triclini c space group P1BAR (No.2) with a = 6.410(1) angstrom, b = 12.227(1) a ngstrom, c = 16.212(3) angstrom, alpha = 79.80(1)degrees, beta = 81.40 (1)degrees, gamma = 84.13(1)degrees, Z = 2. trans-[(NH3)2Pt(1-MeT-N3)( 9-MeA-N7)]ClO4.2.5H2O (5) crystallizes in the same space group P1BAR ( No. 2) with a = 13.527(3) angstrom, b = 19.264(5) angstrom, c = 9.383( 1) angstrom, alpha = 91.24(1)degrees, beta = 103.03(1)degrees, gamma = 74.94(2)degrees, Z = 4. trans-[(NH3)2Pt(2-NH2-py)(9-MeGH-N7)](NO3)2 ( 10) (2-NH2-py = 2-aminopyridine) crystallizes in the monoclinic space group P2(1)/c (No. 14) with a = 14.265(6) angstrom, b = 9.264(4) angst rom, c = 15.321(6) angstrom, beta = 108.25(3)degrees, Z = 4. In 4', th e two complementary bases 1-methylthymine (deprotonated at N3) and 9-m ethyladenine are arranged in a Watson-Crick fashion, while in 5 they a dopt a Hoogsteen arrangement. In both cases a (partial) disorder of th e 1-MeT ligand cannot be excluded from X-ray data. With 5, variable te mperature H-1 NMR spectroscopy in DMF-d7 has been applied to demonstra te the existence of rotamers (Hoogsteen and reversed Hoogsteen arrange ment of the nucleobases) in solution. Common structural features of 4' , 5, and 10 are an approximately coplanar arrangement of the two heter ocyclic ligands, a marked nonlinearity of the base-Pt-base' angle (dev iation as much as 173.4(2)degrees in 4'), and H bonding between the tw o bases. This H bonding occurs between exocyclic groups of the bases i ntramolecularly in 5 and 10 and via a water molecule in 4'. Structural changes of the adenine, thymine base pair upon metal modifications ar e discussed in detail, extended to other metals (Ag(I), Hg(II)), and g eneralized to other possible metal coordination geometries. The format ion of metal-modified base pairs, with regard to DNA cross-linking and related topics, is discussed.