New Sulfur-Containing Polyarsenicals from the New Caledonian Sponge Echinochalina bargibanti.

Petri Tähtinen,Ines Mancini,Edouard Hnawia,Graziano Guella,Cécile Debitus,Giacomo Saielli

doi:10.3390/md16100382

Abstract

Arsenicin A (C3H6As4O3) was isolated from the New Caledonian poecilosclerid sponge Echinochalina bargibanti, and described as the first natural organic polyarsenic compound. Further bioguided fractionation of the extracts of this sponge led us to isolate the first sulfur-containing organic polyarsenicals ever found in Nature. These metabolites, called arsenicin B and arsenicin C, are built on a noradamantane-type framework that is characterized by an unusual As–As bonding. Extensive NMR measurements, in combination with mass spectra, enabled the assignment of the structure for arsenicin B (C3H6As4S2) as 2. The scarcity of arsenicin C and its intrinsic chemical instability only allowed the collection of partial spectral data, which prevented the full structural definition. After the extensive computational testing of several putative structures, structure 3 was inferred for arsenicin C (C3H6As4OS) by comparing the experimental and density functional theory (DFT)-calculated 1H and 13C NMR spectra. Finally, the absolute configurations of 2 and 3 were determined with a combined use of experimental and time-dependent (TD)-DFT calculated electronic circular dichroism (ECD) spectra and observed specific rotations. These findings pose great challenges for the investigation of the biosynthesis of these metabolites and the cycle of arsenic in Nature. Arsenicins B and C showed strong antimicrobial activities, especially against S. aureus, which is comparable to the reference compound gentamycin.

Highlights

Inorganic arsenic compounds are ubiquitous on earth and in the atmosphere
Raw dichloromethane extracts of the residue from ethanol treatment of lyophilized E. bargibanti were subjected to bioassay-guided silica flash chromatography (FC)
Despite the absence of an obvious chromophore, these metabolites are UV absorbent at relatively high wavelengths similar to their synthetic analogues [18], which is a feature that has been elegantly simulated by time-dependent density functional theory (DFT)

Summary

Introduction

Inorganic arsenic compounds are ubiquitous on earth and in the atmosphere. Natural organoarsenicals are found, originating from the conversion of inorganic arsenic forms by a wide variety of marine organisms and including volatile, non-volatile, and water-soluble polar metabolites [1]. Studies have revealed the high affinity of arsenic for sulfur in both natural and synthetic processes [2]. The essential roles played by thiol groups in the metabolic pathways of arsenic involve the ability of this element to bind thiol groups of sulfur-rich peptides (i.e., glutathione) and proteins, resulting in compromised protein folding [3,4,5,6,7]. Arsenic biotransformations are catalyzed by enzymes that are present in diverse environmental organisms, and are coupled to the biogeochemical cycles of some other elements, including sulfur [8].

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