Multi-component click strategy for 1,4-dithiane-2,5-diol based peptoid–triazole conjugates: a combined synthetic and computational study

Abstract

Peptoids and triazoles are N-based organic compounds that have gained immense attention owing to their wide range of applications in pharmaceutical chemistry, drug discovery and materials science. In the present study, we focused on the synthesis of a terminal alkyne-containing peptoid (5) using dithiane as an aldehyde source via a Ugi-4CR multi-component approach. This peptoid with a clickable handle was subjected to a copper-catalysed alkyne–azide click approach to afford the peptoid–triazole products 7a, 7b and 7c. The newly prepared peptoid–triazole conjugates were characterized through spectroscopic techniques. Moreover, the compounds were analysed through density functional theory calculations at the B3LYP/6-311G(d,p) setup using Gaussian 09 and Gauss View 5.0 software. The frontier molecular orbital analysis and global reactivity parameters were investigated to analyse the electronic transitions and molecular stability. In addition, nonlinear optical, natural bond orbital, natural population analysis, density of states, electron localization function, localized orbital locator and molecular electrostatic potential analyses were performed to analyse different properties, such as optoelectronic properties, molecular orbitals, charge distribution and surface properties of the newly synthesized compounds. The theoretical studies revealed that compound 7a exhibited higher reactivity than 7b and 7c with the lowest energy gap and presence of an electron-withdrawing Cl group at the meta position.