Proton NMR study of the binding of bis(acridines) to d(AT)5.cntdot.d(AT)5. 2. Dynamic aspects

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Abstract
Measurments of the 1H NMR spectra and relaxation ratyes were used to study the dynamic properties of 9-aminoacridine (9AA) and 4 bis(acridine) complexes with d(AT)5-d(AT)5. The behavior of the 9AA (monointercalator) and that of C8 (bisintercalator containing an 8 carbon atom linker chain) are entirely similar. For both compounds, the lifetime of the drug in a particular binding site is 2-3 ms at .apprx. 20.degree. C, and neither affects the A.cntdot.t base pair opening rates. The complex with C10 (bisintercalator containing a 10 carbon atom linker chain) is slightly more stable than the C8 complex since its estimated binding site lifetime is 5-10 ms at 29.degree. C. Base pairs adjacent to the bound C110 are destabilized, relative to free d(AT)5-d(AT)5, but other base pairs in the C10 complex are little affected. Bis(acridine) pyrazole (BAPY) and bis(acridine) spermine (BAS) considerably stabilize those base pairs that are sandwiched between the 2 acridine chromophores, but in the BAS complex proton exchange from the 2 flanking base pairs appears to be accelerated, relative to free d(AT)5-d(AT)5. The lifetime of these drugs in specific binding sites is too long (> 10 ms) to be manifested in increased line widths, at least up to 41.degree. C. Certain bisintercalators rapidly migrate along DNA, despite having large binding constants (K > 106 M-1). For C8 and C10 complexes, migration rates are little different from those deduced for 9AA. The rigid linker chain in BAPY and the charge interactions in BAS retard migration of these 2 bisintercalators. These results provide new parameters that are useful in understanding the biochemical and biological properties of these and other bisintercalating drugs.