X-ray structural characterization of the bis-guanine derivative of a cisplatin analogue having just one proton on each coordinated nitrogen and a head-to-head conformation: [Pt{(+/-)-N,N'-dimethyl-2,3-diaminobutane}(9-ethyl-guanine)2]dinitrate.
The X-ray structural and NMR characterization of a bis-guanine derivative of a cisplatin analogue designed to reduce the rate of the Pt-N7 rotation of the coordinated guanine nucleobases by more than 1-million-fold is reported. The [Pt{(+/-)-Me(2)dab}(9-EtG)(2)](NO(3))(2) (Me(2)dab = N,N'-dimethyl-2,3-diaminobutane, 9-EtG = 9-ethyl-guanine) complex crystallizes in the P2(1)/n space group, and the crystal contains a racemic mixture of complex molecules. The data were collected at 120 +/- 2 K, and the crystal and molecular structure (comprising one disordered nitrate) were resolved and refined to conventional agreement factors of R1 = 0.0270 and wR2 = 0.0565. The guanine ligands assume the less common head-to-head (HH) orientation, disclosing full details of the intramolecular relationships between cis guanines and between guanine and cis amine. Moreover, an understanding has been gained of the steric factors determining induction of asymmetry (from carbons to adjacent nitrogen atoms) and puckering of the chelate ring (delta or lambda for R,S,S,R or S,R,R,S configurations at the N,C,C,N chelate-ring atoms, respectively) within the Me(2)dab ligand. The chemical shift separation between H8 signals of the two HT atropisomers and between the two H8 signals of the single HH atropisomer can be explained in terms of canting of the nucleobases relative to the coordination plane and in terms of the different relationships between the H8 proton of one guanine and the shielding zone of the cis guanine. Furthermore, for each configuration of the Me(2)dab ligand (R,S,S,R or S,R,R,S), the NMR data indicate that the handedness of canting is similar for the two guanines in all three (two HT and one HH) conformers (R canting for R,S,S,R and L canting for S,R,R,S configuration).
Intini
Francesco P
FP
Dipartimento Farmaco-Chimico, Università di Bari, Via E. Orabona 4, 70125 Bari, Italy.
Cini
Renzo
R
Tamasi
Gabriella
G
Hursthouse
Michael B
MB
Marzilli
Luigi G
LG
Natile
Giovanni
G
D000970:Antineoplastic Agents / Q000737:chemistry*; D002945:Cisplatin / Q000031:analogs & derivatives*; D018360:Crystallography, X-Ray; D006147:Guanine / Q000031:analogs & derivatives*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D009584:Nitrogen / Q000737:chemistry*; D011522:Protons
D000970:Antineoplastic Agents; D011522:Protons; D006147:Guanine; D009584:Nitrogen; D002945:Cisplatin