title: Computational studies of Fe(III) binding to bryostatins, bryostatin analogs, siderophores and marine natural products: arguments for ferric complexes in medicinal applications.
abstract: In this computational study, geometric factors are calculated by applying semi-empirical methods (PM3) that support experimental evidence from this lab where bryostatins can bind trivalent iron with six Fe-O bonds forming an octahedral geometry. The geometric factors are calculated for all 20 structures (Fe3+ bound to bryostatin 1-20) as a neutral, monovalent, and divalent species. The average Fe-O bond distances and bond angles are compared to those of known marine and terrestrial siderophores. From these two data sets, we then examined other known marine natural products (MNPs) that can form a hexavalent complex with six Fe-O bonds and draw conclusions about their potential biological role as marine siderophores. This computational data indicates that Fe(III) strongly bonds to a host of MNPs, increasing their water solubility, contracting their structure, hence allowing transport through cell membranes more readily, and in some cases, stabilizing ester bonds that are susceptible to hydrolysis. It is argued that administering medicinally bryostatin, its analogs or other MNPs as a ferric complex, holds some fundamental chemical advantages compared to its administration as a neutral uncomplexed species.
authors.affiliation: Department of Chemistry, Valdosta State University, Valdosta, GA 31698, USA. tmanning@valdosta.edu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Manning
authors.forename: Jessica
authors.initials: J
authors.lastname: Thomas
authors.forename: Stephen
authors.initials: S
authors.lastname: Osiro
authors.forename: Justin
authors.initials: J
authors.lastname: Smith
authors.forename: Giso
authors.initials: G
authors.lastname: Abadi
authors.forename: Lyn
authors.initials: L
authors.lastname: Noble
authors.forename: Dennis
authors.initials: D
authors.lastname: Phillips
mesh_terms: D000818:Animals; D001688:Biological Products / Q000737:chemistry*; D054713:Bryostatins / Q000737:chemistry*; D002013:Bryozoa / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry*; D017262:Siderophores / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D001688:Biological Products; D054713:Bryostatins; D005290:Ferric Compounds; D009942:Organometallic Compounds; D017262:Siderophores