Importance of tautomers in the chemical behavior of tetracyclines
Importance of tautomers in the chemical behavior of tetracyclines
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DOI：
10.1021/js980181r
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发表时间：
1999-01-01
影响因子：
3.8
通讯作者：
Simas, AM
中科院分区：
文献类型：
--
作者：
Duarte, HA;Carvalho, S;Simas, AM
我们提出的概念，互变异构是至关重要的理解四环素的化学行为;事实上，考虑到四个去质子化，有64个不同的可能的互变异构体被认为是四环素。我们的研究结果表明，四环素是一个非常适应性的分子，能够很容易地修改自己通过互变异构反应，以应对各种化学环境。事实上，它在溶液中的情况可以更准确地描述为多种互变异构体之间的平衡-这种平衡可以很容易地根据各种可能的化学扰动而被取代，例如改变溶剂的pH值或介电常数。此外，我们还表明，四环素可以进行四次去质子化，并预测它的第四个pK（a）为13，并参考我们的实验测定这个参数，它产生的值为12。我们得出结论，互变异构是必不可少的理解四环素的化学行为所确定的半经验方法AM 1以及自洽反应场方法，估计溶剂对互变异构体的影响。所有的互变异构体在其不同的构象已充分优化的每一个可能程度的质子化的这个分子。因此，不同的互变异构物种的相对稳定性进行了计算。
We advance the concept that tautomerism is crucial for the understanding of the chemical behavior of tetracycline; Indeed, considering four deprotonations, there are 64 different possible tautomers to be considered for tetracycline. Our results indicate that tetracycline is a very adaptive molecule, capable of easily modifying itself through tautomerism in response to various chemical environments. Indeed, its situation in solution can be more accurately pictured as an equilibrium among a diversity of tautomeric species-an equilibrium that can be easily displaced depending on the various possible chemical perturbations, such as varying the pH or the dielectric constant of the solvent. Moreover, we also show that tetracycline could undergo four deprotonations and predict for it a fourth pK(a) of 13 and refer to our experimental determination of this parameter, which yielded the value of 12. We conclude that tautomerism is essential to the comprehension of the chemical behavior of tetracycline as determined by the semiempirical method AM1 as well as by the self-consistent reaction field method, which estimates the effects of the solvent on the tautomers. All tautomers in their different conformations have been fully optimized for each of the possible degrees of protonation of this molecule. Thus, the relative stabilities of the different tautomeric species have been computed.