Currently, urea is widely believed to unfold proteins by increasing the solubility of the amide backbone through direct interactions rather than through global changes in solvent water structure. Urea is thought to enhance hydrogen bonding or van der Waals interactions, thereby increasing the solubility of the amide backbone. However, there are few experimental data to confirm any of these proposed mechanisms. In this work, we first investigated the effects of urea addition on the hydrogen bonding network of water by measuring how it perturbs the fluorescence spectra of the 1-aminonaphthalene (1-AN) and 1-dimethylaminonaphthalene (1-DMAN) molecules involved in hydrogen bonding. In both cases, the fluorescence spectra of the two molecules show that the hydrogen bonding properties of the solvent are minimally affected by the addition of urea from the solute point of view. We have also studied the effects of urea addition on intra-molecular hydrogen bonding as represented by the carboxylate-hydroxyl bond in salicylic acid. Our measurements show that the addition of urea has no effect on the strength of the intra-molecular hydrogen bonds. Finally, we investigate how the addition of urea perturbs the solvation energy of amide moieties in water by comparing the urea-induced changes in the solubility of acetaminophen and 4-tertbutylphenol. Our measurements show that the addition of urea has no appreciable effect on the hydrogen bonding interactions between amide and solvent. Rather, we show that the increase in amide solvation enthalpy correlates linearly with the change in solvent packing density. This confirms the enhanced van der Waals interactions between the solvent and dissolved amide groups in binary urea-water mixtures (relative to pure water). The results of work presented here clearly confirm the theoretical calculations that identify an increase in van der Waals interactions between solvent and amide as the main mechanism for protein denaturation.