text: In many cases, the Benesi–Hildebrand method provides excellent linear plots, and reasonable values for K and ε. However, various problems arising from experimental data have been noted from time to time. Some of these issues include: different values of ε with different concentration scales, lack of consistency between the Benesi–Hildebrand values and those obtained from other methods (e.g. equilibrium constants from partition measurements), and zero and negative intercepts. Concerns have also surfaced over the accuracy of the Benesi–Hildebrand method as certain conditions cause these calculations to become invalid. For instance, the reactant concentrations must always obey the assumption that the initial concentration of the guest ([G]) is much larger than the initial concentration of the host ([H]). In the case when this breaks down, the Benesi–Hildebrand plot deviates from its linear nature and exhibits scatter plot characteristics. Also, in the case of determining the equilibrium constants for weakly bound complexes, it is common for the formation of 2:1 complexes to occur in solution. It has been observed that the existence of these 2:1 complexes generate inappropriate parameters that significantly interfere with the accurate determination of association constants. Due to this fact, one of the criticisms of this method is the inflexibility of only being able to study reactions with 1:1 product complexes.
  These limitations can be overcome by using a computational method which is more generally applicable, a non-linear least-squares minimization method. The two parameters, K or ε are determined by using the Solver module a spreadsheet, by minimizing a sum of squared differences between observed and calculated quantities with respect to the equilibrium constant and molar absorbance or chemical shift values of the individual chemical species involved. The use of this and more sophisticated methods have the additional advantage that they are not limited to systems where a single complex is formed.