Molecular Recognition of Aromatic Rings by Flavin: Electrostatics and Dispersion Determine Ring Positioning above Isoalloxazine
Molecular Recognition of Aromatic Rings by Flavin: Electrostatics and Dispersion Determine Ring Positioning above Isoalloxazine
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DOI：
10.1021/jp407193c
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发表时间：
2013-12-05
影响因子：
2.9
通讯作者：
Lightstone, Felice C.
中科院分区：
文献类型：
--
作者：
Koziol, Lucas;Kumar, Neeraj;Lightstone, Felice C.
用Monte Carlo模拟退火方法研究了黄素异咯嗪（伊萨）与苯、吡啶、氯苯等典型芳烃的堆积相互作用.用有效碎片势（EFP）方法确定了三种二聚体体系的低能平衡构型。这些结构通过DFT（M06-2X）和MP2计算进一步表征。ISA-苯存在一种平衡构型;表征堆叠的二聚体表面揭示了陡峭的单井电位，其直接在环II和III之间漏斗化苯，将取代基氢定位在氧化还原活性N5附近。ISA-吡啶和ISA-氯苯的最低能量结构包含的芳环在非常相似的位置，在ISA-苯。然而，增加的旋转自由度导致两个不同的结合基序，具有与伊萨近似反平行或平行的偶极矩排列。后者的结合配置的存在是出乎意料的，但解释的伊萨静电势的形状。分散是主要的非共价相互作用驱动的伊萨以上的芳环的定位，而静电确定在偶极含取代苯的取向。这些相互作用的相互作用可用于调节合成氧化还原辅因子的分子识别性质，包括将所需官能团定位在氧化还原活性N5附近。
Aromatic stacking interactions between isoalloxazine (ISA) of flavin and three prototypical aromatics (benzene, pyridine, chlorobenzene) were investigated using electronic structure calculations with Monte Carlo simulated annealing. The Effective Fragment Potential (EFP) method was used to locate the low-energy equilibrium configurations for the three dimer systems. These structures were further characterized through DFT (M06-2X) and MP2 calculations. One equilibrium configuration exists for ISA-benzene; characterizing the stacked dimer surface revealed a steep, single-welled potential that funnels benzene directly between rings II and III, positioning a substituent hydrogen adjacent to the redox-active N5. ISA-pyridine and ISA-chlorobenzene minimum-energy structures contain the aromatic ring in very similar position to that in ISA-benzene. However, the added rotational degree of freedom leads to two distinct binding motifs, having approximately antiparallel or parallel dipole moment alignment with ISA. The existence of the latter binding configuration was unexpected but is explained by the shape of the ISA electrostatic potential. Dispersion is the primary noncovalent interaction driving the positioning of aromatic rings above ISA, while electrostatics determine the orientation in dipole-containing substituted benzenes. The interplay of these interactions can be used to tune molecular recognition properties of synthetic redox cofactors, including positioning desired functional groups adjacent to the redox-active N5.