Chlorofullerene C60Cl6: a precursor for straightforward preparation of highly water-soluble polycarboxylic fullerene derivatives active against HIV

Abstract

We report for the first time the application of chlorofullerene C60Cl6 as a substrate for straightforward preparation of highly water-soluble fullerene derivatives, promising compounds for investigation of the biological action of fullerenes in vitro and in vivo. Methyl esters of phenylacetic and benzylmalonic acids were used as reagents in the Friedel-Crafts arylation of C60Cl6 that resulted in the corresponding C60(Ar)5Cl compounds with 50-60% yields. The following cleavage of ester groups in phenylacetic and benzylmalonic residues was accomplished almost quantitatively to yield the corresponding fullerene-based acids bearing 5 and 10 carboxylic groups, respectively. The relatively-low solubility of these acids in water can be strongly enhanced (up to 150-200 mg ml(-1)) by their conversion to salts with alkali metal cations. These fullerene salt derivatives showed pronounced anti-HIV action and low toxicity; these two findings point to the necessity for further investigation of the biological properties of the here-reported compounds.

Synthesis and Orthogonal Functionalization of [60]Fullerene e,e,e‐Trisadducts with Two Spherically Defined Addend Zones

“…[33] This outcome correlates well with the generalized observation that at least three ionic charges with an appropriate arrangement at the fullerene surface or some combination of net charging and other polar moieties is required for sufficient water solubility. [33,[45][46][47][48][49] Selective functionalization of the polar addend zone: For the selective functionalization of the polar addend zone, the focal benzene moiety has to be removed first. In principle, this removal could be achieved through suitable disconnection reactions that cleave the ether or ester bonds in 13-15.…”

Binding of novel fullerene inhibitors to HIV-1 protease: insight through molecular dynamics and molecular mechanics Poisson–Boltzmann surface area calculations

“…A thorough understanding of the interactions between HIV-1 PR and the inhibitor may facilitate the design of more potent drugs. Troshina et al [15] have synthesized fullerene derivatives with improved water solubility that appear to be potent HIV-1 PR inhibitors, indicating strong interactions with the active site residues. Furthermore, Promsri et al [16] have studied the molecular and electronic properties of fullerene-based compounds used as HIV-1 PR inhibitors.…”

Synthesis and antiviral activity of highly water-soluble polycarboxylic derivatives of [70]fullerene

“…The estimated solubility of the potassium salt of 2a (2aK) in water was about 150-200 mg ml À1 which corresponds to the highest values reported for the water-soluble fullerene derivatives in the literature. [4][5][6][7] Compounds 2a-b and their salts are very interesting materials for biomedicinal research and applications. The spider-shaped molecules of these compounds possess a large non-functionalized sp 2 -carbon area on the fullerene cage that might induce hydrophobic or other kinds of interactions with the biological targets (Fig.…”

“…We have addressed this problem recently and reported efficient methods for preparation of water-soluble fullerene derivatives in bulk quantities via photochemical amination reaction of pristine C 60 5 or starting from chlorinated fullerene C 60 Cl 6 and replacing chlorine atoms by cationic 6 or anionic groups. 7 Water-soluble derivatives of [70]fullerene remain poorly investigated. Initial reports suggested that biological properties of [70]fullerene derivatives, in particular their antiviral activity, remain inferior in comparison with the existing C 60 -based analogs.…”