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Slowly Exchanging cis ‐PtA 2 B 2 Atropisomers with A 2 = Chiral Diamine Ligands and B = 5,6‐Dimethylbenzimidazole
Author(s) -
Trani Manuela,
Cannito Francesco,
Natile Giovanni,
Marzilli Patricia A.,
Marzilli Luigi G.
Publication year - 2005
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.200500044
Subject(s) - chemistry , conformational isomerism , denticity , stereochemistry , ligand (biochemistry) , atropisomer , adduct , amine gas treating , diamine , substituent , guanine , crystallography , crystal structure , molecule , nucleotide , organic chemistry , biochemistry , receptor , gene
cis ‐PtA 2 G 2 complexes, in which A 2 is a bidentate amine ligand and G is a unidentate guanine derivative bound to platinum through N7, are simple models of the G‐G cross‐link DNA lesion formed by the anticancer drug cisplatin. Rotation of the G bases about the Pt–N7 bonds is usually rapid except for bulky amine ligand(s). This paper concerns cis ‐PtA 2 (Me 2 Bzm) 2 adducts [A 2 = 2,2'‐bipiperidine (Bip)and N , N , N' , N' ‐tetramethyl‐2,3‐diaminobutane (Me 4 DAB); Me 2 Bzm = 5,6‐dimethylbenzimidazole] for which the interconversion among possible rotamers (one HH and two HT) is slow on the NMR time scale. The amounts of the rarely observed HH conformer were 52 and 37 % at 5 °C for BipPt(Me 2 Bzm) 2 and Me 4 DABPt(Me 2 Bzm) 2 , respectively, and increased to 60 and 44 % at 50 °C. This result represents the first reported clear evidence for the existence of the HH atropisomer in cis ‐PtA 2 B 2 adducts (B = G or Me 2 Bzm base) with fully substituted diamines, such as Me 4 DAB or Me 4 EN (Me 4 EN = N , N , N' , N' ‐tetramethyl‐1,2‐diaminoethane). The lack of an O‐substituent on the C4 atom of Me 2 Bzm (corresponding to C6 of G) undoubtedly allows for a relatively stable HH conformer. Thermodynamic parameters confirm the crucial role of the substituents in positions 4 and 6 of the base systems (for Me 2 Bzm and G derivatives, respectively) in determining the stability of different rotamers. The greater abundance of the HH rotamer for BipPt(Me 2 Bzm) 2 than for Me 4 DABPt(Me 2 Bzm) 2 indicates that an increase in the steric bulk of the carrier ligand favors the HT rotamers over the HH rotamer. For both BipPt(Me 2 Bzm) 2 and Me 4 DABPt(Me 2 Bzm) 2 adducts, the major HT rotamer has the six‐membered ring of each Me 2 Bzm ligand on the more crowded side of the cis amine with respect to the platinum coordination plane: the N–CH 2 – group in Bip and the N–Me eq (N–Me eq = quasi‐equatorial N–Me) in Me 4 DAB adducts. The latter result is in complete agreement with previous findings from our laboratories concerning BipPtG 2 and Me 4 DABPtG 2 compounds and gives further support to the view that the major HT rotamer is stabilized by the six‐membered ring of each base canted toward the cis base. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)