Chiral generation in achiral lower diamondoid triamantane through prochiral halogen substitution.

Context: Our work demonstrates the chiral and chiroptical behavior of lower diamondoid molecules such as triamantane. Through the halogen substitution prochirality process, chirality was attained from the achiral triamantane molecule. The chiroptical behavior of chiral triamantane obtained from VCD, ROA, and ORD analysis evidences the significant chiral activity for all halogen substitutions ranging from fluorine to iodine for both S and R enantiomers. These chiral and chiroptical characteristics of the triamantane enantiomers can be tuned well through various halogen substitutions. The absolute configurations for chiral triamantane molecules are identified through the Cahn-Ingold-Prelog rule together with VCD analysis. The optical rotatory dispersion (ORD) of chiral triamantane molecules is dominant for chlorine, bromine, and iodine substitutions. Chiral triamantane molecules with various halogen substitutions also find a prominent role in pharmacology through their anisotropic charge distribution and binding abilities, tunable lipophilicity, nominal synthetic accessibility, and good bioavailability score.

Methods: The absolute configurations for chiral triamantane molecules are identified through the Cahn-Ingold-Prelog rule. To study the chiroptical behavior of chiral triamantane molecules, wB97XD and M06-2X DFT functionals are employed, and for the initial guesses, 6-311G(d,p) and MidiX basis sets are used.