Water splitting involves the synergistic operation of water oxidation and hydrogen evolution half-reactions and remains a considerable challenge since it requires the concerted transfer of four electrons and four protons. Catalysts that can facilitate both of the half-reactions at low overpotentials are imperative to avoid squandering free energy harvested using a semiconductor in a photoelectrochemical cell, or provided directly in the form of current in a water electrolyzer. Photocatalytic water splitting requires the operation of light harvesting, charge separation, charge transport, and redox catalytic steps that must outcompete charge recombination. As such, it requires the precise tunability of energetic offsets to establish optimal thermodynamic driving forces for charge transfer and control of interfaces to mediate kinetics of charge transfer. The talk will focus on the design of compounds with the composition M
xV2O5 where M is a post-transition metal cation with lone-pairs characterized by intercalative mid-gap states that can accept holes from photoexcited semiconductor quantum dots. Such compounds, accessible through topochemical intercalation of metastable polymorphs of V2O5, have facilitated the design of heterostructures with energetic offsets primed to facilitate effective hole transfer upon photoexcitation of the heterostructures, thereby mitigating the longstanding challenge of the anodic photocorrosion of quantum dots. Interfacial design further provides a means of modulating the dynamics of hole transfer, which occurs at <1 ps timescales. The second half of the talk will focus on discussing the specific electronic structure characteristics of edge sites of MoS2 that enable them to function as catalysts for the hydrogen evolution reaction. Interfacial hybridization of MoS2 with nC60 provides a means to modulate the electronic structure and enhance catalytic activity. Interfacing MoS2 with semiconductor quantum dots further yields effective photocatalysts for hydrogen evolution that have been examined using operandoX-ray absorption spectroscopy. The two examples illustrate the potential of computationally driven materials design to unravel new physical insights and provide practical solutions to challenges in hydrogen generation. The authors acknowledge support from the NSF under DMREF-1627197, DMREF-1626967, and DMREF-1627583 as well as from the NSF DMREF/ DOE EERE EMN project.