The Complexation of Tetracycline and Anhydrotetracycline with Mg²⁺ and Ca²⁺:  A Spectroscopic Study

Abstract

Steady-state absorption and emission, circular dichroism (CD), and time-of-flight secondary-ion-mass-spectroscopic (TOF−SIMS) measurements were performed to study the complexation of tetracycline (TC) and anhydrotetracycline (AHTC) with Mg2+ and Ca2+ ions, respectively, in aqueous solutions at pH 8.02. The results obtained suggest that Ca2+ forms a 1:2 ligand:metal complex with TC via chelation through O10−O11 and O12−O1 and induces thereby the extended conformation A of TC, which is stabilized through hydrogen bonding between the deprotonated dimethylamino nitrogen, N4, and OH12a. pH titrations provide evidence that N4 deprotonates in the presence of a 164-fold molar excess of Ca2+ at approximately pH ⩾ 7.7 (c TC = 2.1 × 10-5 M). In contrast to Ca2+, Mg2+ binds to N4−O3 and thereby stabilizes the twisted conformation B of TC. TOF−SIMS measurements indicate that a 1:2 ligand:metal complex is formed in addition to the 1:1 complex. The Mg2+-induced increase in the fluorescence intensity and the observed changes in the absorption spectra provide evidence that the other Mg2+ ion binds to the BCD ring system through the deprotonated O11. In contrast to TC, which adopts the twisted conformation B in aqueous solution at pH 8.02, AHTC exhibits the extended conformation A due to slightly lower deprotonation constants. In the presence of Mg2+, however, the conformational equilibrium is shifted toward the twisted conformation B due to binding of Mg2+ to N4. TOF−SIMS measurements suggest that a 2:2 ligand:metal complex is formed. AHTC remains in conformation A upon addition of Ca2+; complexation through O10 can be excluded on the basis of absorption spectroscopic data.

Comparative study of oxytetracycline and doxycycline on calcium chelation: in-vitro assay

“…In study a conducted by Wessels et al the results obtained suggest that Ca 2+ forms a 1:2 ligand: metal complex with TC. 9 In current study, by both the methods we found that oxytetracycline chelates calcium and these findings are comparable with earlier studies. The base line calcium concentration was found to be 10 mg/dl.…”

Sorption and desorption of tetracycline on layered manganese dioxide birnessite

“…The difference between the d-spacings of TC-intercalated and TC-dehydrated birnessite is about 4.3 Å . Generally accepted conformations for TC were extended and twisted forms, with the former primarily existing in basic solution when the dimethylamino group lies below the plane spanned by the ring system (Wessels et al 1998), while the latter was present in acidic-to-neutral solutions when the dimethylamino group lies above the ring system (Wessels et al 1998;Duarte et al 1999;Othersen et al 2003). In the twisted form, TC was 12.9 Å long, 7.5 Å wide, and 6.2 Å high, occupying an area of 97 Å 2 when the ring was parallel to the surface (Gambinossi et al 2004).…”

Tetraciclinas e glicilciclinas: uma visão geral

“…[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] Nesse contexto, estudos teóricos têm sido realizados por alguns de nós, relacionados à interação do derivado 5a,6-anidrotetraciclina (AHTC) com cátions metálicos. [42][43][44][45][46] Esses trabalhos têm auxiliado os experimentalistas nas propostas para os possíveis sítios de coordenação, como evidenciado nos trabalhos de Wessels et al 47 e Vogler et al, 40 envolvendo complexos de AHTC com Mg(II) e Pt(II), respectivamente.…”