Sulfur Derivatives of the Natural Polyarsenical Arsenicin A: Biologically Active, Organometallic Arsenic–Sulfur Cages Related to the Minerals Realgar and Uzonite

Abstract

±)-Arsenicin A (AsA), (±)-1, the first natural polyarsenical to be isolated, has the adamantane-type structure of the mineral arsenolite (As 4 O 6 ), in which three of the oxygen atoms have been replaced by methylene groups to give an organometallic, arsenic− oxygen cage of C 2 symmetry. Heating of a benzene solution of AsA with aqueous sodium sulfide produces, by reductive desulfurization of the intermediate sulfur analog (±)-2, the monosulfide cage (±)-4, which contains two As−As bonds and which has a C 2 -chiral cage structure related to the mineral realgar (α-As 4 S 4 ). At room temperature the reaction affords a chiral disulfide derivative that exists as a pair of separable diastereomers, (±)-3a and (±)-3b, each of which contains a single As−As bond and is structurally related to the mineral uzonite (As 4 S 5 ). The crystal structures of the monosulfide (±)-4 and the diastereomeric disulfides (±)-3a and (±)-3b have been determined. As for AsA, the sulfur derivatives exhibit strong UV absorptions and can be resolved on a Chiralpak IA column. The monosulfur cage (±)-4 is considerably more potent and more selective than AsA and the current "arsenical gold standard", arsenic(III) oxide as Trisenox, against the acute promelocytic leukemia cells (NB4) and certain solid cancer cell lines.

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

“…A comparison between the experimental and calculated 1 H spectra of structure B6 is given in Supplementary Figure S5 . After the extensive testing of several putative structures of the disulfurated arsenicin B, the computational study found agreement for structure B6 , which is the one assigned by experimental data and supported by the X-ray analyzed synthetic compound [ 21 ].…”

“…It is noteworthy that arsenicin B corresponds to one of the four sulfur derivatives obtained when synthetic arsenicin A was treated with an aqueous solution of sodium sulfide in benzene [ 21 ]. The NMR data of the metabolite isolated from E. bargibanti extract are practically superimposable to those reported for the racemic ( R *As, S *As, R *As, R *As)-dihydro-3H-2,6-epithio(1,2,4)triarsolo-(1,2-b)(1,2,3,5) thiatriarsole, which was structurally determined by X-ray diffraction after racemate resolution by chiral column chromatography.…”

“…On the other hand, the emergence of multiple drug-resistant strains of bacteria due to the indiscriminate use of antibiotics has induced an urgent need of developing additional strategies to treat bacterial infections. It is also to note that the synthetic polyarsenical with the composition C 3 H 6 As 4 S displayed values of proliferation inhibition that were higher than arsenicin A on ovarian and breast cancer cell lines [ 21 ]. These findings may open new perspectives in considering polyarsenicals with one or more sulfur atoms as potential applications in drug development.…”

New Sulfur-Containing Polyarsenicals from the New Caledonian sponge Echinochalina bargibanti

“…A comparison between the experimental and calculated 1 H spectra of structure B6 is given in Supplementary Figure S5. After the extensive testing of several putative structures of the disulfurated arsenicin B, the computational study found agreement for structure B6, which is the one assigned by experimental data and supported by the X-ray analyzed synthetic compound [21]. Finally, the absolute configuration of arsenicin B was determined by comparing its experimental and time-dependent density functional theory (TD-DFT) calculated electronic circular dichroism (ECD) spectra ( Figure S6).…”

State-of-the-art and recent developments of immobilized polysaccharide-based chiral stationary phases for enantioseparations by high-performance liquid chromatography (2013–2017)

“…have also been determined, especially in commercial products or biological samples (pharmaceutical formulations, human urine, human or animal blood, human plasma, animal serum, etc.). Another heterogeneous group of analytes, including connectors for building metal-organic frameworks [116,117,124], intermediates for the synthesis of pharmaceuticals [111], natural and synthetic compounds [39,113,121,120], biological compounds [82,112,58,71,78,86,[61][62][63]77,75], natural alkaloids [121], biomolecules [115,54], organometallic compounds [119] and chiral metabolites [103,108,100,97,102,59,63,52] has been enantioseparated with these immobilized polysaccharides CSPs (see Table 2-4). Fig.…”