Dumbbell-Type Fullerene-Steroid Hybrids: A Join Experimental and Theoretical Investigation for Conformational, Configurational, and Circular Dichroism Assignments

Abstract

New [60]fullerene-steroid conjugates (4-6) have been synthesized by 1,3-dipolar cycloaddition and Bingel-Hirsch cyclopropanation reactions from suitably functionalized epiandrosterone and [60]fullerene. Since a new stereocenter is created in the formation of the Prato monoaduct, two different diastereomers were isolated by HPLC (4, 5) whose absolute configurations were assigned according to the highly reliable "sector rule" on fullerenes. A further reaction of the malonate-containing diastereomer 5 with a second C60 molecule has afforded dumbbell fullerene 6 in which the two fullerene units are covalently connected through an epiandrosterone moiety. The new compounds have been spectroscopically characterized and their redox potentials, determined by cyclic voltametry, reveal three reversible reduction waves for hybrids 4 and 5, whereas these signals are split in dumbbell 6. Theoretical calculations at semiempirical (AM1) and single point B3LYP/6-31G(d) levels have predicted the most stable conformations for the hybrid compounds (4-6), showing the importance of the chlorine atom on the D ring of the steroid. Furthermore, TDDFT calculations have allowed assignments of the experimentally determined circular dichroism (CD) of the [60]fullerene-steroid hybrids based on the sign and position of the Cotton effects, despite the exceptionally large systems under study.

Steroid–Fullerene Hybrids from Epiandrosterone: Synthesis, Characterization and Theoretical Study

“…[25] Employing cholesterol, or cholesterol derivatives, attached to [60]fullerene through a pyrrolidine ring, some hybrids have been described, demonstrating that the steroid moiety can confer useful solubility in components of biological fluids, impacting on the biodistribution of the fullerenes, which makes these derivatives useful in imaging, diagnosis, and in the treatment or in management of disease. [32] In continuation with our interest in the chemistry of fullerene hybrids, here we report on the design of new steroid-fullerene hybrids using the naturally occurring epiandrosterone as the starting material due to its well known biological activity as Ltype Ca + channels antagonist [33] which may increase the ability of C 60 to cross the cell membrane envelopes, [34] and could be used in treatment of cardiovascular diseases. [28] Actually, a hybrid steroid-fullerene has been employed for developing a [60]fullerene modified electrode as a sensitive voltammetric sensor for detection of nandrolone, an anabolic steroid used in doping.…”

1,3-Dipolar Cycloaddition Reactions of Azomethine Ylides with Carbonyl Dipolarophiles Yielding Oxazolidine Derivatives

“…Azomethine ylides are mostly generated in situ due to their high reactivity and/or transient existence; however, in some cases, stabilized ylides have been isolated [19][20][21]. The most frequent type of 1,3-dipolar cycloaddition reaction of azomethine ylides is that with alkenyl or alkynyl dipolarophiles substituted with electron-withdrawing groups, providing access to pyrrolidine-containing molecules of biological [18,[22][23][24][25][26] or materials science interest [27][28][29][30][31]. The reactions with multiple bonded heteroatom systems such as carbonyl, thiocarbonyl, isothiocyanato, imino, isocyanato, nitrile, nitroso, and azo derivatives are also known, but less well studied [7,16,[32][33][34][35][36][37][38].…”

Pyrrolyl–Silicon Compounds as Precursors for Donor–Acceptor Systems Stabilized by Noncovalent Interactions

“…Multiple Minima Hypersurface (MMH) methodology, which validity for the study of molecular associations and for conformational analysis has been widely demonstrated by some of the co-authors, [30][31][32][33][34][35][36][37][38] was employed for random generation and optimization at semiempirical level of theory of α−α'Py n SiOH (n = 2,3). Most stable structures were DFT-refined for conformational analysis.…”