. In this work, an ion mobility spectrometer, constructed in our laboratory was used, to experimentally study the thermodynamic of proton bond dimer formation MH + +M®MHM + , at atmospheric pressure. The reaction is considered as one of the preliminary steps in dissolving protonated molecules. In addition, ab initio calculation was performed to back the experimental results. First, the geometry of the reactant and products for methyl-isobutyl-keton, (MIBK) was optimized using Gaussian 98. Then the enthalpies and Gi free energies were calculated using Hartree-Fock method with 6-311++G** basis set. The calculation was then carried out using B 3 LYP method to obtain more accurate results. The calculation yielded a -28.5 kcal/mol for enthalpy change of reaction. In the second part, the enthalpy change for reaction was determined by measuring the equilibrium constant at different temperatures using Van’t Hoff plot. To establish equilibrium in the ionization region, the sample flow rate was increased until the reaction quotient (Q) was independent of the flow rate. The relative abundances of the monomer and dimer were obtained from the intensity of their corresponding peaks in the mobility spectrum to be used in calculation of the equilibrium constant, K=[MHM + ]/ [MH + ][M]. The Van’t Hoff plot resulted in about -5kcal/mol for D H q which is far from the theoretical value of -25kcal/mol. The reason for such big difference was attributed to hydration of ions in atmospheric pressure. In fact, a series of multiequilibrium reactions, rather than a simple reaction happens in IMS. A model was proposed to solve this complicated system. Based on the results obtained from the calculation, a mixture of protonated monomers, MH + (H 2 O) n with different n’s was considered to be in equilibrium with unhydrated dimer, MHM + with equilibrium constant of K n . Hence, a reduced equilibrium constant of K as; K Red =1/S( p n / K n ) was defined for the whole reaction as well as a reduced enthalpy change of D H q Red =SY n D H q n , where Y n = ( p n / K n )/S( p n / K n ) and p is the partial pressure of water. Y is the portion of each reaction n, in the whole reaction which depends on the water vapor pressure and temperature. The reduced enthalpy is defined as the enthalpy change for formation of one mole dimer from any root. Since, D H n ’ s have different values, and Y is temperature dependent, the reduced enthalpy will be strongly affected by temperature so that it may even change its sign to positive at low temperatures.