9-methylguanine and 9-methyladenine

The dirhenium complex Re2(i-C3H7COO)4Cl2 was synthesized and characterized by X-ray crystallography, (1)H NMR and electronic spectroscopies, and electrospray ionization-mass spectrometry. The reactions of Re2(i-C3H7COO)4Cl2 with the substituted DNA purine nucleobases guanine (9-methylguanine and 9-ethylguanine) and adenine (9-methyladenine and 9-ethyladenine) were investigated by proton nuclear magnetic resonance and electronic spectroscopies as well as electrospray ionization-mass spectrometry. The data corroborate binding of two 9-methylguanine (or 9-ethylguanine) and 9-methyladenine (or 9-ethyladenine) bases per dirhenium unit in a bidentate fashion, in equatorial positions, via sites N7/O6 and N1/N6, respectively, with concomitant substitution of two carboxylate groups to form a single isomer of cis-Re2(i-C3H7COO)2(nucleobase)2Cl2. The binding of the bases to the dirhenium core disrupts important nucleobase interactions and may have important biological implications with respect to the anticancer activity of dirhenium complexes.

Topics: Adenine; Coordination Complexes; Crystallography, X-Ray; DNA; Guanine; Liposomes; Proton Magnetic Resonance Spectroscopy; Rhenium; Solubility; Spectrometry, Mass, Electrospray Ionization

The transition structures (TS) between H-bonded (H) and stacked (S) structures of 9-methyladenine...1-methylthymine and 9-methylguanine...1-methylcytosine base pairs were localized at the DFT-D/TZVP potential energy surface. The energy barrier between the S and TS structures is considerably higher for the former pair than for the latter, which makes localization of the stacked structure of this pair possible.

Topics: Adenine; Base Pairing; Cytosine; Guanine; Hydrogen Bonding; Models, Molecular; Thermodynamics; Thymine

Guanine-guanine hydrogen bonding involving the Watson-Crick edge [N(1)H, N(2)H2] of one base and the Hoogsteen edge (N7, O6) of the other is the dominant association pattern in the solid-state structures of two hydrates of 9-ethylguanine (9-EtGH), and in adducts of 9-methylguanine (9-MeGH) with the Zn compounds [ZnCl2(H2O)(9-MeGH-N7)]*(9-MeGH) as well as [ZnCl2(H2O)(9-MeA-N7)]*2(9-MeGH) (9-MeA is 9-methyladenine). The structures of 9-EtGH*2H2O and 9-EtGH*3.5H2O are dominated by polymeric tape structures of the guanine and extended water clusters. In [ZnCl2(H2O)(9-MeGH-N7)]*(9-MeGH) the metalated guanine is involved in hydrogen bonding (GG3 motif) with a free 9-MeGH, which in turn is centrosymmetrically related to itself via hydrogen bonds involving N2H2 and N3 (GG4 motif). In [ZnCl2(H2O)(9-MeA-N7)]*2(9-MeGH) the metalated adenine base interacts via its Watson-Crick edge [N1, N(6)H2] with the sugar edge [N(2)H2, N3] of one of the guanine nucleobases of the GG pair. Crystallization of [ZnCl2(H2O)(9-MeA-N7)]*2(9-MeGH) from an aqueous solution containing 9-MeGH, 9-MeA, and ZnCl2 is fully unexpected in that the anticipated preference of Zn(II) for guanine-N7 is not realized and instead coordination to adenine-N7 is observed. The relevance of [ZnCl2(H2O)(9-MeGH-N7)]*(9-MeGH) and [ZnCl2(H2O)(9-MeA-N7)]*2(9-MeGH) for metal-containing nucleic acid triplex structures is discussed.

Topics: Adenine; Crystallography, X-Ray; Guanine; Hydrogen Bonding; Models, Molecular; Molecular Structure; Stereoisomerism; Water; Zinc

Planar H-bonded and stacked structures of guanine...cytosine (G.C), adenine...thymine (A...T), 9-methylguanine...1-methylcytosine (mG...mC), and 9-methyladenine...1-methylthymine (mA...mT) were optimized at the RI-MP2 level using the TZVPP ([5s3p2d1f/3s2p1d]) basis set. Planar H-bonded structures of G...C, mG...mC, and A...T correspond to the Watson-Crick (WC) arrangement, in contrast to mA...mT for which the Hoogsteen (H) structure is found. Stabilization energies for all structures were determined as the sum of the complete basis set limit of MP2 energies and a (DeltaE(CCSD(T)) - DeltaE(MP2)) correction term evaluated with the cc-pVDZ(0.25,0.15) basis set. The complete basis set limit of MP2 energies was determined by two-point extrapolation using the aug-cc-pVXZ basis sets for X = D and T and X = T and Q. This procedure is required since the convergency of the MP2 interaction energy for the present complexes is rather slow, and it is thus important to include the extrapolation to the complete basis set limit. For the MP2/aug-cc-pVQZ level of theory, stabilization energies for all complexes studied are already very close to the complete basis set limit. The much cheaper D-->T extrapolation provided a complete basis set limit close (by less than 0.7 kcal/mol) to the more accurate T-->Q term, and the D-->T extrapolation can be recommended for evaluation of complete basis set limits of more extended complexes (e.g. larger motifs of DNA). The convergency of the (DeltaE(CCSD(T)) - DeltaE(MP2)) term is known to be faster than that of the MP2 or CCSD(T) correlation energy itself, and the cc-pVDZ(0.25,0.15) basis set provides reasonable values for planar H-bonded as well as stacked structures. Inclusion of the CCSD(T) correction is essential for obtaining reliable relative values for planar H-bonding and stacking interactions; neglecting the CCSD(T) correction results in very considerable errors between 2.5 and 3.4 kcal/mol. Final stabilization energies (kcal/mol) for the base pairs studied are very substantial (A...T WC, 15.4; mA...mT H, 16.3; A...T stacked, 11.6; mA...mT stacked, 13.1; G...C WC, 28.8; mG...mC WC, 28.5; G...C stacked, 16.9; mG...mC stacked, 18.0), much larger than published previously. On the basis of comparison with experimental data, we conclude that our values represent the lower boundary of the true stabilization energies. On the basis of error analysis, we expect the present H-bonding energies to be fairly close to the true values, while

Topics: Adenine; Base Pairing; Cytosine; Guanine; Hydrogen Bonding; Models, Chemical; Models, Molecular; Thermodynamics; Thymine

The Pt-L bond energies of simple triammineplatinum(II) complexes, [Pt(NH(3))(3)L](2+), with oxygen-, nitrogen-, and sulfur-containing donor ligands L have been predicted and rationalized using density functional theory. The ligands L have been chosen as models for functionalities of peptide side chains, for sulfur-containing protecting agents, and for adenine and guanine sites of the DNA as the ultimate target of platinum anticancer drugs. Calculation of the Pt-L bond energy in [Pt(NH(3))(3)L](2+) reveals that the soft metal center of triammineplatinum(II) prefers N ligands over S ligands. This remarkable result has been discussed in light of several interpretations of the hard and soft acids and bases principle. The concept of orbital-symmetry-based energy decomposition has been employed for the determination of the contributions from sigma and pi orbital interactions, electrostatics, and intramolecular hydrogen bonding to the Pt-L bond energy. The calculations show that considerable differences in the bond energies of the triammineplatinum(II) complexes with N-heterocycles such as 1-methylimidazole, 9-methyladenine, and 9-methylguanine arise from electrostatics rather than from orbital interactions. Surprisingly, the net stabilization by hydrogen bonding between the (Pt)N-H group and the oxygen of 9-methylguanine is as weak as the intramolecular hydrogen bond in the aqua complex [Pt(NH(3))(3)(H(2)O)](2+), challenging the common hypothesis that DNA-active anticancer drugs require carrier ligands with N-H functionalities because of their hydrogen-bonding ability. The influence of a polarizable environment on the stability of the complexes has been investigated systematically with the dependence of the dielectric constant epsilon. With increasing epsilon, the complexes with S-containing ligands are more strongly stabilized than the complexes of the N-containing heterocycles. At epsilon = 78.4, the dielectric constant of water, 9-methylguanine remains the only purine derivative investigated which is competitive to neutral sulfur ligands. These findings are particularly important for a rationalization of the results from recent experimental studies on the competition of biological donor ligands L for coordination with the metal center of [Pt(dien)L](2+) (dien = 1,5-diamino 3-azapentane).

Topics: Adenine; Antineoplastic Agents; Cisplatin; DNA Adducts; Guanine; Imidazoles; Ligands; Molecular Structure; Peptides; Static Electricity