(Thia)calix[n]arenes have been widely applied as molecular platforms and host molecules in supramolecular chemistry due to their high level of preorganization and well-detectable conformational preferences. Here we report on quantum chemical calculations allowing the conformational analysis of p-substituted calix[4]-, calix[6]-, thiacalix-[4]-, and thiacalix[6]arenes. To this effect, ab initio and density functional theory (DFT) calculations with the aid of RHF/3-21G, B3LYP/6-31G, B3LYP/6-31G(d,p), and B3LYP/6-311G(d,p) have been applied. The obtained structural data and the estimated energies of the intramolecular hydrogen bonds give clear evidence of the presence of cooperative effects of the hydrogen bonding Multiple correlations between the pairs of Hammett constants of substituents and the calculated values of hydrogen bond energies in the corresponding p-substituted (thia)calix[n]arenes have been found. These energies can be considered as descriptors of a chemical reactivity of the p-substituted derivatives of (thia)calix[n]arenes. For example, the reaction of nucleophilic substitution, involving p-substituted. calix[6]arenes in the presence of weak bases and in aprotic solvents or in the gas phase, under orbital control conditions should, proceed through the diastereomeric transition states. Here, the achiral p-substituted calix[6]arene derivative mainly forms as an intermediate product of the reaction with a substrate without asymmetric centers.