title: Role of the B-ring substituent in the fluorescence of colchicinoid-tubulin and allocolchicinoid-tubulin complexes.
abstract: Fluorescence spectra of several B-ring derivatives of allocolchicine in a variety of solvents have been obtained. The quantum yields of the allocolchicine derivatives decreased with amine substitution at the C-7 position [R = H greater than NH2 much greater than NHCH3 greater than N(CH3)2]. The relative fluorescent intensities of the aminoallocolchicinoids [R = NH2, NHCH3, N(CH3)2] bound to tubulin were significantly less than the fluorescent intensities of tubulin-bound allocolchicine (R = NHCOCH3) and deacetamidoallocolchicine (R = H). The low fluorescent intensities of the aminoallocolchicinoids in solvents and bound to tubulin could be explained by exciplex formation between the lone pair of electrons on the nitrogen and the allocolchicinoid pi-system, which leads to quenching of the allocolchicinoid fluorescence. Direct evidence for exciplex formation between the C-7 amine nitrogen and the allocolchicinoid pi-system was found in the emission spectrum of N-methyldemeallocolchicine [R = N(CH3)2] in dioxane. The quantum yields of the aminoallocolchicinoids in glycerol were higher than would be predicted on the basis of solvent dielectric effects. Glycerol appears to increase the quantum yields of the aminoallocolchicinoids through both viscosity and hydrogen-bonding effects. The latter effect serves to sequester the lone pair of electrons on the nitrogen, decreasing its ability to interact with the pi-system of the allocolchicinoid. It is concluded that the fluorescent properties of colchicinoids and allocolchicinoids in glycerol are not reliable indicators of the fluorescent properties of the molecules bound to tubulin.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Chemistry, State University of New York, Binghamton 13902-6000.
authors.forename: E A
authors.initials: EA
authors.lastname: Pyles
authors.forename: S B
authors.initials: SB
authors.lastname: Hastie
mesh_terms: D003078:Colchicine / Q000031:analogs & derivatives* / Q000737:chemistry*; D005454:Fluorescence Polarization; D008024:Ligands; D014404:Tubulin / Q000737:chemistry*
chemical_list: D008024:Ligands; D014404:Tubulin; C032782:allocolchicine; D003078:Colchicine