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Stacking and edge‐to‐edge associations of antitumoral ellipticine derivatives are controlled in solution by interactions involving their nitrogen sites
Author(s) -
Sizun P.,
Auclair C.,
Lescot E.,
Paoletti C.,
Perly B.,
Fermandjian S.
Publication year - 1988
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360270704
Subject(s) - chemistry , chromophore , stacking , steric effects , nitrogen , stereochemistry , crystallography , methyl group , photochemistry , group (periodic table) , organic chemistry
1 H chemical shift dilution experiments on the cytotoxic drugs 2‐methylellipticinium 1 and its methylated still active analogues 2,6‐dimethylellipticinium 2 and 1,2‐dimethylellipticinium 3 indicate that the three chromophores autoassociate in dimers, trimers, and larger aggregates. The results suggest that the same chromophores are both stacked via transannular π interactions and associated edge to edge via interactions involving the nitrogen atoms such that layer structures similar to those observed in crystals could be formed at high concentration. Substitution with a methyl group on the N 6 position or the C 1 position near the N 2 + , results in analogues displaying an association constant significantly reduced when compared to parent compound 1 . This decrease is attributed to the loss or strength weakening of the forces involving nitrogen atoms rather than to the steric influence of the methyl substituents on the stacking of chromophores. The results are further discussed in terms of the various modes of binding of the ellipticines to DNA.