There is recurrent interest in the orbital angular momentum (OAM) conveyed by optical vortices, which are structured beams with a helically twisted wave front. Particular significance is attached to the issue of how material interactions with light conveying OAM might prove sensitive to the handedness and degree of twist in the optical wave front. As a result of recent experimental and theoretical studies, the supposition that beams with OAM might enable spectroscopic discrimination between oppositely handed forms of matter has become a renewed focus of attention. Some of the tantalizing conclusions that are beginning to emerge from this research have, however, not yet established a definitive basis for a supporting mechanism. To resolve this problem requires the development of theory to support a faithful representation, and a thorough understanding, of the fundamental molecule-photon physics at play in such optical processes - even for processes as basic as absorption. The present analysis establishes mechanisms at play that entail an unconventional manifestation of optical spin-orbit interactions, engaging transition electric-quadrupole moments. Powerful symmetry principles prove to render distinctively different criteria governing the exhibition of two-dimensional (2D) and 3D chirality. These results elucidate the operation of such effects, identifying their responsibility for discriminatory optical interactions of various forms in both chiral and achiral media.