Dehydrochlorination of Hexachlorocyclohexanes Catalyzed by the LinA Dehydrohalogenase. A QM/MM Study

详细信息    查看全文

• 作者：Rabindra Nath Manna ; Kirill Zinovjev ; I帽aki Tu帽贸n ; Agnieszka Dybala-Defratyka
• 刊名：Journal of Physical Chemistry B
• 出版年：2015
• 出版时间：December 10, 2015
• 年：2015
• 卷：119
• 期：49
• 页码：15100-15109
• 全文大小：511K
• ISSN：1520-5207

文摘

The elucidation of the catalytic role of LinA dehydrohalogenase in the degradation processes of hexachlorocyclohexane (HCH) isomers is extremely important to further studies on the bioremediation of HCH polluted areas. Herein, QM/MM free energy simulations are employed to provide the details of the dehydrochlorination reaction of two HCH isomers (纬 and 尾). In particular, the role of the protonation state of one of the catalytic residues鈥擧is73鈥攊s explored. Based on our calculations, two distinct minimum free energy pathways (concerted and stepwise) were found for 纬-HCH and 尾-HCH. The choice of the reaction channel for the dehydrochlorination reactions of 纬- and 尾-HCH was shown to depend on the initial mutual orientations of the reacting species in the active site and the protonation form of His73. The sequential pathway comprises the transfer of the proton (H_未1) between His73 and Asp25 and subsequently the H₁/Cl₂ pair elimination from the substrate molecule. Within a concerted mechanism, the dehydrochlorination reaction of 纬-/尾-HCH is initiated with neutral His73 and the H_未1 proton is transferred upon final product formation. We found that the concerted pathway for 尾-HCH results in significantly higher free energy of activation than the stepwise route and therefore can be disregarded as not a feasible mechanism. On the other hand, the reaction that occurs with much lower energetic barrier requires a stronger base (i.e., anionic His73) to abstract the proton (H₁) from the substrate molecule. The presence of such transient form of His results in higher energy than the respective Michaelis complex and was observed only in the stepwise pathway for both isomers. Furthermore, we have concluded that both pathways (concerted and stepwise) are feasible for the dehydrochlorination reaction of 纬-HCH. The activation free energies obtained from the M05-2X/6-31+G(d,p) corrected path coordinate PMF profiles for the dehydrochlorination reactions of the 纬-/尾-HCH are in good agreement with the experimental values.