Solvent- and concentration-dependent molecular interactions of taxol (Paclitaxel).
Taxol (paclitaxel) is a promising anticancer agent that has been approved for the treatment of ovarian cancer and is under investigation for the therapy of other tumors. Paclitaxel is poorly soluble in water, and information on its physical behavior in hydrophilic and hydrophobic environments is limited. Circular dichroism (CD) and nuclear magnetic resonance spectroscopy were used to investigate the effect of solvent and drug concentration on the solution conformation of paclitaxel. CD is sensitive to paclitaxel's environment, owing to the presence of effective chromophores in the vicinity of several chiral centers. It was found that (i) the conformation of the paclitaxel side chain depends on the polarity of the solvent and (ii) paclitaxel has a tendency to undergo concentration-dependent aggregation in solvents such as chloroform. To account for the observations, a model is proposed in which paclitaxel molecules are held together in stacks by intermolecular hydrogen bonds involving all four exchangeable protons. Intermolecular interactions and self-association of paclitaxel may have impact not only on the physical stability of the drug in existing formulations or investigational vehicles but also on the effect of paclitaxel in the stabilization of cellular microtubules.
Balasubramanian
S V
SV
Department of Pharmaceutics, University at Buffalo, State University of New York, Amherst 14260-1200.
Alderfer
J L
JL
Straubinger
R M
RM
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D009994:Osmolar Concentration; D017239:Paclitaxel / Q000737:chemistry*; D012997:Solvents
D012997:Solvents; D017239:Paclitaxel