Propane is one of several hydrocarbons known to form a clathrate hydrate. To probe interactions leading to clathrate nucleation, the water-propane interaction is investigated in carbon tetrachloride with infrared spectroscopy. Isotopic substitution provides compelling evidence that the water-propane interaction occurs between the propane methylene hydrogen atoms and the water lone pair. In addition, interaction between propane and water results in clustering of water molecules, a clustering that is identified by the appearance of a peak between the symmetric and asymmetric stretches of water.