Structural studies of tetracyclines. Crystal and molecular structures of anhydrotetracycline hydrobromide monohydrate and 6-demethyl-7-chlorotetracycline hydrochloride trihydrate

Abstract

The crystal and molecular structures of two tetracyclines, anhydrotetracycline hydrobromide ( I ) and 6-demethyl-7chlorotetracycline hydrochloride (11) have been determined by x-ray diffraction techniques. Aromatization of the C ring of tetracyclines gives I but also destroys any useful therapeutic value. In contrast I I has excellent antibacterial properties. The crystals of I monohydrate are orthorhombic, space group P212121 with unit cell dimensions of a = 19.562 (2). b = 16.586 (2), and c = 6.796 (2) A. Crystals of I I as the trihydrate are monoclinic, space group P21, with cell dimensions of a = 9.219 ( I ) , b = 11.634 ( I ) , c = I 1.240 ( I ) A; /3 = 102.39 (4)". Although the conformation of I is similar to that of 11, significant differ-

The structure and absolute configuration of viridicatumtoxin: 2'S-(2'α,7'aβ,11'aβ,12'β)-7',7'a,8',11',11'a,12'-hexahydro-5',6',7'a,10',11'a,12'-hexahydroxy-3'-methoxy-2,6,6-trimethyl-7',8'-dioxospiro[2-cyclohexene-1,2'(1'H)-cyclopenta[de]naphthacene]-9'-carboxamide methanolate

“…The present authors favor the latter explanation since maximum directions of apparent thermal parameters appear to be at right angles to the planar system, as may be seen in Fig. 1 for viridicatumtoxin and as appears to be the case in the OR TEP drawings published by Stezowski (1976), and Palenik, Mathew & Restivo (1978). If tautomeric mixtures were present, one might expect the apparent maximal directions of the thermal ellipsoids to be in the plane of the bonds, as was the case in the tautomeric mixture of tropolones reported by Iorio, Brossi & Silverton (1978).…”

“…Name Ionicity R x R 2 R 3 Carboxamide (1) As discussed by Stezowski (1976), and Palenik, Mathew & Restivo (1978), there have been two conformations reported for the A ring of the tetracyclines. The most common conformation occurs in all the ionic and zwitterionic compounds reported in Table 3 which do not have perturbations caused by further ring formation.…”

Binding of the Highly Toxic Tetracycline Derivative, Anhydrotetracycline, to Bovine Serum Albumin

“…31) On the basis of our fluorescence results, we postulate that AHTC would bind to a buried binding site excluded from water in subdomain IIA. This tentative binding location correlates with the big, planar and aromatic structure of AHTC 13,14) and the predominant anionic form of the drug.…”

“…12) Dehydration leads to significant changes in aromatization and planarity of the tetracyclic moiety, 13,14) showing variations in potency, 15) mechanism of action 1) and lipophilicity 16,17) as compared to the parent compound. Changes in chemical configuration can also modulate the interaction of drugs with serum proteins.…”

Electronic properties of two adjacent intramolecular hydrogen bonds and their effects to the molecular charge distribution: Experimental synchrotron microcrystal and DFT computational study

“…Both hydrogen bonds are designated as the S(6) motif according to Etter [16] (Table 1). Short intramolecular O-H…O hydrogen bonds in the vicinity of a second intramolecular N-H…O hydrogen bond have 5 already been observed and reported for a few structures [17][18][19][20]. In addition, an intermolecular hydrogen bond contact (N1-H1B…O1 i ) is observed, that links two neighboring molecules by a center of inversion.…”