“…Williamson and Everett suggested that complexation occurs at the tricarbonyl methane moiety when DMSO is used as a solvent . Similar discrepancies regarding the assignments of the chelation sites for Cu 2+ and Co 2+ can be found in the literature. ,, …”
Section: Introductionsupporting
confidence: 57%
“…Tetracyclines (TCs) (Scheme ) form reversible complexes with metal ions as well as with substances of low and high molecular weight. The complexation behavior determines to a large extent their biological action. − The complex deprotonation pattern of TCs as well as the large number of possible chelation sites has led to extensive studies on the complexation of various TC derivatives with several different metal ions in aqueous and organic environments using nuclear magnetic resonance spectroscopy, ,− circular dichroism spectroscopy, ,− absorption and fluorescence spectroscopy, ,,, as well as electroanalytical methods. − 1 Chemical Structures and Abbreviations Used…”
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.
“…Williamson and Everett suggested that complexation occurs at the tricarbonyl methane moiety when DMSO is used as a solvent . Similar discrepancies regarding the assignments of the chelation sites for Cu 2+ and Co 2+ can be found in the literature. ,, …”
Section: Introductionsupporting
confidence: 57%
“…Tetracyclines (TCs) (Scheme ) form reversible complexes with metal ions as well as with substances of low and high molecular weight. The complexation behavior determines to a large extent their biological action. − The complex deprotonation pattern of TCs as well as the large number of possible chelation sites has led to extensive studies on the complexation of various TC derivatives with several different metal ions in aqueous and organic environments using nuclear magnetic resonance spectroscopy, ,− circular dichroism spectroscopy, ,− absorption and fluorescence spectroscopy, ,,, as well as electroanalytical methods. − 1 Chemical Structures and Abbreviations Used…”
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.
“…The interaction of tetracycline derivatives with metal ions has been the object of several studies using different investigation techniques, such as nuclear magnetic resonance spectroscopy, 18,19 circular dichroism spectroscopy, 20,21 electroanalytical methods, [22][23][24][25][26] calorimetry, 27,28 absorption and fluorescence spectroscopy. [29][30][31][32][33][34] The results reported in the literature are somehow controversial regarding the stoichiometries of the complexes and the binding sites on the substrate for the cations.…”
Section: Introductionmentioning
confidence: 99%
“…40 The complex structures of Mg 2+ and Ca 2+ in the binding process with tetracyclines have already been proposed for almost neutral aqueous solutions. 23,[41][42][43][44] It has already been observed by using stationary and time resolved fluorescence 15,16 that the binding of Mg 2+ and Ca 2+ leads to enhance strongly the fluorescence intensity and to increase the excited state lifetimes.…”
Spectroscopic techniques both in steady-state (in absorption and emission) and pulsed (absorption of excited states with femtosecond resolution) conditions were used to study the complexation process between six molecules belonging to the tetracycline family and Mg(2+); in the case of TC the study was extended to the metal ions Ca(2+) and Cu(2+). The study was carried out in aqueous solution at various pH values, where one acid-base form of the substrate prevails over the others. The processing of experimental results, performed by means of Singular Value Decomposition and Global Analysis methods, allowed us to evaluate the extent of interaction through the association constants, to identify the number of equilibria present in solution and the stoichiometry (1:1 or 1:2) of the tetracycline:metal ion complex, and to define the spectral and photophysical properties of the latter (in terms of fluorescence quantum yields, lifetimes and rate constants). In fact, the (allowed) radiative decay process is a minor root for the lowest excited state of the complexes which mainly decay to the ground state by internal conversion. Details of the complexation sites are proposed for the various protonated forms of tetracyclines, and for the various cations in the case of TC. In particular, the molecular structure seems to affect significantly the dynamics of interaction when the upper peripheral region of tetracycline is rich in additional hydroxyl groups. Moreover, the state of protonation of the substrate produces changes in the order of the complexation sites, whose affinity for the cation increases significantly when they are negatively charged owing to the loss of protons. Magnesium and calcium (hard cations) give similar interactions, at least in acid solution, while copper(ii) (borderline cation) binds more efficiently on different sites, thus forming complexes with different properties.
“…Devido ao facto de, na sua estrutura química, existir um grande número de possíveis locais de ligação, as TC em solução formam, com grande facilidade, complexos metálicos. Como tal, nos fluidos biológi-cos, o seu mecanismo de acção é fortemente dependente da presença de iões metálicos 2 . Alguns trabalhos anteriormente descritos na literatura mostram que, a presença de co-factores (iões metálicos) deve ser considerada na avaliação do mecanismo de acção das TC em sistemas biológicos, embora o seu papel no desenvolvimento da acção antibacteriana ainda não esteja bem definido.…”
Recebido em 20/4/99; aceito em 17/11/99
TETRACYCLINE, OXYTETRACYCLINE AND CHLORTETRACYCLINE COMPLEXATION WITH COPPER (II). POTENTIOMETRIC STUDY. Stability constants of complexes formed by copper (II) with three different tetracyclines (tetracycline, oxytetracycline and chlortetracycline)have been determined potentiometrically with an automatic system in aqueous medium at 25,0 ± 0,2 o C and I = 0,1 mol L -1 NaNO 3 . The protonation constants of the three tetracyclines were also determined under the same conditions. The distribution of the complexes was then simulated at therapeutic levels of the drugs.Keywords: tetracycline; copper (II); complex formation.
ARTIGO
INTRODUÇÃOAs Tetraciclinas (TC) representam uma das mais importantes famílias farmacológicas e, tendo em conta o seu largo espectro de acção antibacteriano, são usadas, como tratamento de primeira escolha, nas infecções bacterianas causadas por chlamydia, rickettsia, mycoplasma, brucella e spirochaeteae 1 . São ainda frequentemente utilizadas em medicina veterinária, em nutrição animal e em aditivos alimentares destinados a uso pecuário.As Tetraciclinas constituem um grupo de substâncias cristalinas de natureza anfotérica, que contêm um esqueleto comum, hidronaftacénico (Figura 1). Devido ao facto de, na sua estrutura química, existir um grande número de possíveis locais de ligação, as TC em solução formam, com grande facilidade, complexos metálicos. Como tal, nos fluidos biológi-cos, o seu mecanismo de acção é fortemente dependente da presença de iões metálicos 2 . Alguns trabalhos anteriormente descritos na literatura mostram que, a presença de co-factores (iões metálicos) deve ser considerada na avaliação do mecanismo de acção das TC em sistemas biológicos, embora o seu papel no desenvolvimento da acção antibacteriana ainda não esteja bem definido. O conhecimento das interacções sofridas por estes antibióticos com metais poderá ajudar a melhor compreender a sua actuação em mecanismos fisiológicos específicos, bem como a planear métodos de doseamento mais eficazes e rápidos, que possam competir favoravelmente com os métodos oficiais 3,4 .A importância do estudo das interacções desta família de compostos com o catião cobre deve-se ao facto de este metal estar presente em concentrações apreciáveis, quer nos fluidos biológicos quer em preparações multivitamínicas, usualmente administradas durante tratamentos com antibióticos. Além disso, o recurso a métodos de doseamento, baseados na formação de complexos corados das TC com o catião Cu (II) tem sido frequentemente proposto [5][6][7][8] . As propriedades complexantes desta família de drogas têm sido muito estudadas anteriormente contudo, os valores das constantes de estabilidade correspondentes à formação de complexos entre o ião cobre (II) e as TC descritos na literatura não são concordantes 9-11 e nem sempre consideram a existência das mesmas espécies em solução aquosa razão, pela qual estas devem ser reavaliadas.O trabalho apresentado teve como objectivo a determinação das constantes de estabilidade dos...
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