TY - JOUR
T1 - Head-to-head cross-linked adduct between the antitumor unit bis(μN,N′-di-p-tolylformamidinato)dirhodium(II,II) and the DNA fragment d(GpG)
AU - Chifotides, Helen T.
AU - Dunbar, Kim R.
PY - 2006/8/25
Y1 - 2006/8/25
N2 - Reactions of the compound cis-[Rh2(DTolF)2(CH 3CN)6](BF4)2, a formamidinate derivative of the class of antitumor compounds [Rh2(O 2CR)4] (R = Me, Et, Pr), with 9-ethylguanine (9-EtGuaH) or the dinucleotide d(GpG) proceed by substitution of the acetonitrile groups, with the guanine bases spanning the Rh-Rh bond, in a bridging fashion, through sites N7/O6. In the case of 9-EtGuaH, both head-to-head (HH) and head-to-tail (HT) isomers are formed, whereas with the tethered bases in d(GpG), only one right-handed conformer HH1R [Rh2-(DTolF)2{d(GpG)}] is present in solution. For both cis-[Rh2(DTolF)2(9-EtGuaH) 2](BF4)2 and [Rh2(DTolF) 2{d-(GpG)}], the absence of N7 protonation at low pH and the substantial decrease of the pKa values for N1-H deprotonation, support N7/O6 binding of the bases to the dirhodium core. The N7/O6 binding of the bases is further corroborated by the downfield shift by Δδ∼ 4.0 ppm of the 13C NMR resonances for the C6 nuclei as compared to the corresponding resonances of the free ligands. The HH arrangement of the guanine bases in [Rh2(DTolF)2-{d(GpG)}] is indicated by the intense H8/H8 ROE cross-peaks in the 2D ROESY NMR spectrum. Complete characterization of the [Rh2(DTolF)2 {d-(GpG)}] conformer by 2D NMR spectroscopy supports anti-orientation and N (C3′-endo) conformation for both deoxyribose residues. The N-pucker for the 5′-G base is universal in such cross-links, but it is very unusual for platinum and unprecedented for dirhodium HH cross-linked adducts to have both deoxyribose residues in the N-type conformation. The bulk, the nonlabile character, and the electron-donating ability of the formamidinate bridging groups spanning the dirhodium core affect the nature of the preferred dirhodium DNA adducts. Molecular modeling studies performed on [Rh2-(DTolF) 2{d(GpG)}] corroborate the structural features obtained by NMR spectroscopy.
AB - Reactions of the compound cis-[Rh2(DTolF)2(CH 3CN)6](BF4)2, a formamidinate derivative of the class of antitumor compounds [Rh2(O 2CR)4] (R = Me, Et, Pr), with 9-ethylguanine (9-EtGuaH) or the dinucleotide d(GpG) proceed by substitution of the acetonitrile groups, with the guanine bases spanning the Rh-Rh bond, in a bridging fashion, through sites N7/O6. In the case of 9-EtGuaH, both head-to-head (HH) and head-to-tail (HT) isomers are formed, whereas with the tethered bases in d(GpG), only one right-handed conformer HH1R [Rh2-(DTolF)2{d(GpG)}] is present in solution. For both cis-[Rh2(DTolF)2(9-EtGuaH) 2](BF4)2 and [Rh2(DTolF) 2{d-(GpG)}], the absence of N7 protonation at low pH and the substantial decrease of the pKa values for N1-H deprotonation, support N7/O6 binding of the bases to the dirhodium core. The N7/O6 binding of the bases is further corroborated by the downfield shift by Δδ∼ 4.0 ppm of the 13C NMR resonances for the C6 nuclei as compared to the corresponding resonances of the free ligands. The HH arrangement of the guanine bases in [Rh2(DTolF)2-{d(GpG)}] is indicated by the intense H8/H8 ROE cross-peaks in the 2D ROESY NMR spectrum. Complete characterization of the [Rh2(DTolF)2 {d-(GpG)}] conformer by 2D NMR spectroscopy supports anti-orientation and N (C3′-endo) conformation for both deoxyribose residues. The N-pucker for the 5′-G base is universal in such cross-links, but it is very unusual for platinum and unprecedented for dirhodium HH cross-linked adducts to have both deoxyribose residues in the N-type conformation. The bulk, the nonlabile character, and the electron-donating ability of the formamidinate bridging groups spanning the dirhodium core affect the nature of the preferred dirhodium DNA adducts. Molecular modeling studies performed on [Rh2-(DTolF) 2{d(GpG)}] corroborate the structural features obtained by NMR spectroscopy.
KW - Antitumor agents
KW - Bioinorganic chemistry
KW - Formamidinates
KW - N ligands
KW - Nucleic acids
KW - Rhodium
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U2 - 10.1002/chem.200600401
DO - 10.1002/chem.200600401
M3 - Article
C2 - 16900545
AN - SCOPUS:33748565391
SN - 0947-6539
VL - 12
SP - 6458
EP - 6468
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 25
ER -