Perpendicular nanochannel creation of two-dimensional (2D) nanostructures requires highly controlled anisotropic drilling processes of the entire structure via void formation. However, chemical approaches for the creation of porosity and defects of 2D nanostructures have been challenging due to the strong basal plane chemical stability and the use of harsh reactants, tending to give randomly corroded 2D structures. In this study, we introduce Lewis acid-base conjugates (LABCs) as molecular drillers with attenuated chemical reactivity which results in the well-defined perpendicular nanochannel formation of 2D TiS2 nanoplates. With the treatment of LABCs, tris(trimethylsilyl)pnictogens (TMS3P or TMS3As), high resolution perforation of TiS2 nanoplates was achieved while maintaining their initial shape and structures. Such perforated TiS2 nanoplates are tunable in their channel diameter between 4 and 10 nm with 2 nm resolution. With their increased surface area and enhanced adsorption of Li2Sx, perforated TiS2 nanoplates served as a diffusion barrier of lithium-sulfur (Li-S) cells, leading to a 2.5-fold improvement in cell performance compared to pristine TiS2 nanoplates. Our molecular design concept for attenuated reactivity of LABCs is simple and could serve as a new approach for chemical drilling processes of 2D metal chalcogenides.