Rotamer stability in cis-[Pt(diA)G2] complexes (diA = diamine derivative and G = guanine derivative) mediated by carrier-ligand amine stereochemistry as revealed by circular dichroism spectroscopy.
Extensive investigations of cis-[Pt(diA)G2] complexes (in which G = a guanine ligand; diA = a single diamine ligand) revealed the types of interactions between the two G ligands and between the G and the cis-amine substituents when diA is a diamine ligand with substituents on each nitrogen atom being a small hydrogen atom and a bulky group able to slow the rotation about the Pt-G bond. All these interactions are shown to apply also when diA = dach (1,2-diaminocyclohexane), even though this chiral primary diamine has only small N-H atoms on each side of the coordination plane. However, a slight difference in the stereochemistry of the two protons (one N-H has "quasi axial" and the other "quasi equatorial" character) is sufficient to induce a significant change in the relative stabilities of the [Pt(dach)G2] deltaHT and lambdaHT rotamers (HT = head-to-tail). The new results show that at acidic and neutral pH the induction of asymmetry from the dach ligand to the HT rotamers is governed by the G-to-G dipole-dipole interaction, which is greater for the six-membered ring of each guanine leaning towards the cis-G. Such a "six-in" canting of the two guanine ligands can be hampered by the steric interaction between the H8 of each guanine and the substituent on the cis-amine that is on the same side of the coordination plane. Such a repulsion is greater for a "quasi equatorial" N-H than for a "quasi axial" N-H. Under basic pH conditions, deprotonation of the guanine N1-H renders the O6 atom a much better hydrogen-bond acceptor; therefore, the stability of the HT rotamers is governed by the hydrogen-bond interaction of guanine O6 and the cis-amine N-H group. Such a guanine O6/N-H cis-amine interaction is stronger for a "quasi axial" than for a "quasi equatorial" N-H group. In the head-to-head (HH) rotamer, in which the electrostatic repulsion between electron-rich O6 atoms, both on the same side of the platinum coordination plane, tends to place the six-membered rings of each guanine further from the cis-guanine and closer to the cis-amine, we can expect better N-H...O6 hydrogen bonding for the "quasi equatorial" N-H groups.
Benedetti
Michele
M
Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università degli Studi di Lecce, Via Monteroni, 73100 Lecce, Italy.
Marzilli
Luigi G
LG
Natile
Giovanni
G
D000588:Amines / Q000737:chemistry*; D002942:Circular Dichroism / Q000379:methods*; D003959:Diamines / Q000737:chemistry*; D006147:Guanine / Q000737:chemistry*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D017671:Platinum Compounds / Q000737:chemistry*; D013237:Stereoisomerism
D000588:Amines; D003959:Diamines; D008024:Ligands; D017671:Platinum Compounds; D006147:Guanine