CD‐sensitive Zn‐porphyrin tweezer host‐guest complexes, part 1: MC/OPLS‐2005 computational approach for predicting preferred interporphyrin helicity

Abstract

This article describes a computational study on dimeric zinc porphyrin tweezer complexes with primary/secondary amines and secondary alcohols that validates the use of Optimized Potential for Liquid Simulations (OPLS-2005) as the lead computational choice for assisting the tweezer methodology in the absolute configurational assignment of organic compounds. A supramolecular, microscale approach known as the tweezer method has been widely applied in the past decade for determining the absolute configuration of chiral substrates that are difficult to study by other readily available methods. The method relies on a host/guest complexation mechanism between a porphyrin tweezer moiety and a substrate, after its conversion into a bidentate conjugate. The formation of 1:1 complexes is a stereodifferentiating process: upon complexation, the originally achiral tweezer adopts a preferential interporphyrin helicity, dictated by the absolute configuration of the chiral substrate. By correctly predicting the sign of the interporphyrin helicity in the complex, OPLS-2005 provides a correlation between the observed circular dichroism (CD) signal and the absolute configuration of the substrate. It also offers a great degree of insight into the structural factors responsible for chiral recognition and the amplitude of exciton couplets. Moreover, the preferential binding sites between the Zn-tweezer and secondary amine conjugates were revealed by using the new computational approach.

Bulky melamine‐based Zn‐porphyrin tweezer as a CD probe of molecular chirality

“…It was more recently established 6,7 that a preferred interporphyrin helicity of the complex can be predicted by molecular mechanics (MM) calculations using the Monte Carlo (MC) algorithm, so that the correlation of observed exciton CD with AC can be made on more reliable theoretical basis. Molecular modeling conformational investigations are now carried out with the support of the recently developed force field OPLS-2005.…”

A Direct Stereoselective Preparation of a Fish Pheromone and Application of the Zinc Porphyrin Tweezer Chiroptical Protocol in Its Stereochemical Assignment

“…Similarily, the C20 epimer, (20S)-1 , was subjected to conjugation with 7 (Scheme ), followed by deprotection and complexation with the tweezer prior to CD studies. As predicted on the basis of the steric size of the substituents flanking the stereogenic center, as described above, the exciton coupled CD spectrum of the tweezer complex formed from (20R)-1 (compound (20R)-9 ) had a negative exciton couplet, reflective of the negative twist of the transition moments of the porphyrin tweezer and indicative of an ( R ) absolute configuration, whereas the complex formed from (20S)-1 (compound (20 S )‐ 9 ) had a positive couplet, predicting an ( S ) absolute configuration.…”

Exploration of fluoroquinolone resistance in Streptococcus pyogenes: comparative structure analysis of wild‐type and mutant DNA gyrase

“…At this time point, the crude score values and the geometrical filter dissimilar binding modes of the ligands were removed. The second filter stage involves a grid‐based force field evaluation and refinement of docking solutions, including the torsional and the rigid body movements of the ligand, the OPLS‐AA force field was used for this purpose (Kahn and Bruice, , Petrovic et al ., ). A small number of surviving docking solution was subjected to a Monte Carlo procedure for minimized energy score.…”