The rigid duplex cyclodextrin 6 composed of two alpha-cyclodextrin macrocycles connected with two disulfide bonds in "transannular" (C6(I), C6(IV)) positions was prepared from partially debenzylated alpha-cyclodextrin 1 in four steps in 73% overall yield. In the last key step involving oxidative coupling of the thiol 5, predominance of the target duplex 6 can be attained under conditions of thermodynamic control. The structure of duplex cyclodextrin was established by MS as well as 2-D NMR methods and confirmed by a single-crystal X-ray analysis. The ability of the duplex cyclodextrin 6 to bind alpha,omega-alkanediols (C9-C14) and 1-alkanols (C9 and C10) was studied by isothermal titration calorimetry in aqueous solutions. The stability constants of the complexes gradually increase with the alkyl chain length and reach an unprecedently high value of K = 8.6 x 10(9) M(-1) for 1,14-tetradecanediol. It was found that the doubly bridged dimer 6 exhibits higher binding affinity toward the series of alpha,omega-alkanediols than the singly bridged analogue 10 by about 2 orders of magnitude in K (M(-1)) or 3.1-3.3 kcal/mol in deltaG(o), the enhancement being due to enthalpic factors. Theoretical calculations using DFT-D methods suggest that the enthalpic contribution stems from dispersion interactions.