Exploring the interactions of molecules with silica-based mesoporous and nanoparticle materials at the atomic level and understanding of the forces that govern such H-bonds and electrostatic interactions are of fundamental importance to nanocatalysis, nanomedicine, and nanophotonics. In our approach, we studied in single-molecule time and spectral domains a proton-transfer chromophore complexed (by diffusion) and covalently bonded to MCM-41 mesoporous nanomaterial and silica particles. The results reveal strong dependence of the distribution and behavior of the interacting single molecule with the nanopores on the mode of sample preparation and nature of the involved interaction. The change at the single molecule level results in an up to 126 nm (approximately 4650 cm(-1)) spectral shift (from 462 to 588 nm) and almost two times longer lifetime. Furthermore, a change in the electronic charges of the mesoporous framework results in significant narrowing in the emission band of the guest. The results are explained in terms of electronic nanoconfinement but at a single-molecular level.