D-Histidine modulated chiral metal-organic frameworks for discriminating 3,4-Dihydroxyphenylalanine enantiomers based on a chemiluminescence quenching mode

Background: Drug enantiomers often display distinguishable or even opposite pharmacological and toxicologic activities. Therefore it is of great necessity to discriminate enantiomers for guaranteeing safetyness and effectiveness of chiral drugs. Facile chiral discrimination has long been a noticeable challenge because of the minimal differences in physicochemical properties of enantiomers. As one of high-performance chirality selection components, chiral metal-organic frameworks (CMOFs) are bringing new opportunities for the establishment of chiral discrimination platform with merits of high enantioselectivity, low cost, and facile operation.

Results: By introducing D-Histidine as a modulator, a CMOFs material termed as D-Histidine-ZIF-8 was prepared on chitosan (CS) with an in-situ growth protocol. The positively charged CMOFs/CS hybrids were adsorbed onto negatively charged polystyrene microplate via electrostatic interaction to form a chiral discrimination interface. This interface can effectively adsorb 3,4-Dihydroxyphenylalanine (DOPA) enantiomers, and the adsorbed molecules can be quantitated based on their quenching behavior on the chemiluminescent (CL) signal of Co²⁺-catalyzed luminol-H₂O₂ reaction. The results of contact angle measurements and density functional theory calculations imply that CMOFs/CS have stronger affinity towards D-isomer than L-isomer. Thus the sensitivity for quantifying D-isomer is 2.93 times of that for L-isomer, demonstrating the enantioselectivity of the CMOFs/CS hybrids. The content of D-isomer in nonracemic mixtures of DOPA enantiomers and real samples were assayed with satisfactory results, showing the practicality of this method. The strategy also exhibited discrimination capacity for many other chiral molecules.

Significance: The CMOFs/CS hybrids prepared with in-situ growth protocol display satisfactory selectivity for discriminating enantiomers. Due to usage of multi-well microplate platform, the method is anticipated to achieve high-throughput assay in the future work. This study paves a pathway for facile chiral discrimination based on a chemiluminescence quenching mode to meet the demand of drug development and manufacture.