Submitted to: American Chemical Society SE/SW Regional Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 10/3/2006
Publication Date: 11/1/2006
Citation: Thomas, J., Stoney, T., Sermons, S., Mcleod, K., Abandi, G., Roberts, S., Manning, T., Potter, T.L., Philips, D., Rudloe, J., Marshall, A., Barton, I., Bryant, J., Newton, J. 2006. Computational and Experimental Studies On The Hydrolysis of Bryostatin [abstract].American Chemical Society SE/SW Regional Meeting. Interpretive Summary:
Technical Abstract: Bryostatin is a marine natural product studied in over 30 clinical cancer therapy trials. Its large bryophan ring is held together by an ester bond. This study was conducted in three phases. The first phase is a compilation of experimental data obtained with TLC-MALDI-TOF-MS, FT-ICR and LC-MS techniques. This data indicates that, when bryostatin is stored in 95% ethanol (5% H20), hydrolysis takes place and a number of common species (i.e. 806 m/z, 637 m/z, etc.) are observed. These same ions have been observed in extracts from marine organisms and sediment. The second component is an experimental study which monitors the decomposition of bryostatin in chloroform with low levels of H2O present. From this work, rate constants and activation energies are presented. The third set of experiments focuses on computational work that determines the C-O ester bond lengths in bryostatin 1-20 with and without Fe(III) bond to the structure. Experimental data show Fe(III) can bind bryostatin and computational studies suggest its most stable conformation is a hexavalent (6 Fe-O bonds), octahedral structure. These [Bryo-Fe]x (where x=0,1,2) complexes are being investigated to determine if Fe(III) stabilizes the structure against hydrolysis while improving its water solubility.