M. El-Kemary, J. A. Organero, A. Douhal
Jun 1, 2006
Citations
0
Influential Citations
25
Citations
Journal
Journal of medicinal chemistry
Abstract
The fast relaxation dynamics of 1,6-dihydro-2-methyl-6-oxo-3,4'-bipyridine-5-carbonitrile (milrinone, MIR), a cardiotonic drug, has been characterized in water solutions at different pH. In acidic media, a blue emission reflects a charge-transfer state in the cation (C) leading to a more stabilized structure with an emission lifetime of 90 ps. The emission lifetimes of the keto (K) and anion (A) structures are approximately 65 and 310 ps, respectively. Reasons for efficient nonradiative channels are discussed in terms of hydrogen-bonding interactions, intramolecular charge transfer (ICT), and twisting motion. A blue nanosecond-emission observed in almost all the studied pH range is suggested to be due to relaxed K due to an ICT reaction. B3LYP (6-31+G**) calculations showed that, in a water cavity, K is more stable than the enol form by 7 kcal/mol, and the ICT may take place within the pyridone moiety. At the physiological pH, the inotropic K structure is the dominant species (approximately 100%).