Crystal and molecular structure of the barium salt of an antibiotic containing a high proportion of oxygen

Abstract

The molecular structure of an antibiotic X-537A, C34H54O8, from an unidentified streptomyces has been determined by the X-ray structure analysis of a barium salt. Two molecules of the barium salt monohydrate, Ba(CS4H53Os)2 H20, crystallize in the space group P2i with a = 14.59, b = 17.95, c = 13.99 A, and ß = 105°17'. The structure has been refined to an R factor of 0.11 on 4753 structure amplitudes measured by film methods. The two crystallographically independent antibiotic molecules wrap themselves around the barium, with eight oxygen atoms and the water molecule of crystallization in the range 2.6-3.1 Á from the metal ion. Eighteen years ago, three hitherto unknown, crystalline antibiotics were obtained from three unidentified streptomyces, designated X-206, X-464, and X-537A.3 All three antibiotics are optically active organic acids, containing a high proportion of oxygen. These antibiotics are capable of forming a variety of salts with Ag+, Na+, K+, and Ba2+.3 More recently, another antibiotic, monensic acid, was isolated from Streptomyces cinnamonensis, and showed similar high oxygen content and capability to form metal salts.4The structure of monensic acid has been determined by a combination of chemical studies and an X-ray structural analysis of the monosilver salt.4The antibiotic X-537A produced by X-537A has the molecular formula C34H54O8.5 Nmr studies indicate that, while mainly aliphatic, it has two protons in a region indicative of a tetrasubstituted aromatic group, and that there is a methyl group ( = 2.18) which is either bound to an aromatic ring or to a C=C double bond.6 There is no evidence for a methoxyl group;6 monensic acid contains one methoxyl group.4 Mass spectra also provided evidence for the presence of an aromatic ring or of a structure which could readily form such a ring.6 The infrared spectra of the piperidine salt and the free acid both have a band at 1700 cm-1, suggestive of a saturated ketone.6In view of the limited structural evidence available, an X-ray structure analysis of a suitable metal salt was proposed as the most convenient means of structure determination of the antibiotic from X-537A. Furthermore, the conformation of the antibiotic when bound to a metal will be of interest when compared to that of monensic acid. Since the inception of this study, two independent X-ray studies of a related antibiotic, nigericin, have appeared7-8 and chemical studies have shown that nigericin and X-464 are identical.9 A

Conformation and mode of organization of amphiphilic membrane components: a conformational analysis

“…2.5 to 40) over a distance smaller than the ionophore size so that a part of the molecule may stay in a pure hydrophobic environment whereas another part may reach a high-polarity environment. Since its X-ray analysis (Johnson et al, 1970), the conformation of lasalocid A, which complexes alkalis, alkaline earths and amines, has been extensively investigated (Fig. 8a).…”

Catecholamine equilibration gradients of isolated chromaffin vesicles induced by the ionophore X‐537A

“…The ionophore X-537A, a monocarboxylic acid antibiotic, is able to form lipophilic complexes with monovalent and divalent ions [ 1,2] . A number of studies have reported the ability of X-537A to increase calcium fluxes through certain biological membranes such as mitochondria [3] and sarcoplasmic reticulum [4,51. More recently, X-537A has been used to investigate the role of Ca2 + as secretagogue of neurotransmitters and hormones from endogenous stores of perfused organs.…”

Transport of Pr3+ by hypoglycemic sulfonylureas across liposomal membranes

“…This difference in efficiency coincides with a low affinity for Ca2+ of hypoglycemic sulfonylureas (Keq about lo-r4) [7,15] as compared to such ionophores as X537A (Keq = lo-") and A23187 (Keq = 4.10-') [16,17].…”