Dissociation constants of host–guest complexes of alkyl-bearing compounds with β-cyclodextrin and "hydroxypropyl-β-cyclodextrin"

Abstract

Dissociation constants (Kd) of host-guest complexes formed from P-cyclodextrin or "hydroxypropyl-P-cyclodextrin" (P-CD and Hp-P-CD) and several types of aliphatic guests (alcohols, alkanesulfonate ions, alkylamines, and a-amino acids), with up to eight carbons in a chain, are reported. These constants were determined by inhibition kinetics and by a spectrofluorometric displacement method based on competition with 1-anilino-8-naphthalenesulfonate ion as a fluorescent probe. The value of Kd for a particular amine is close to that for the corresponding alcohol. For linear alkyl derivatives, there are strong correlations between pK, (= -log Kd) and the chain length of the guest, with slopes around 0.5, complementing trends that were noted earlier. Furthermore, the strengths of binding of various aliphatic derivatives to P-CD and to Hp-P-CD are close, with Kd values for the two CDs usually being within a factor of 2 of each other. Overall, for the binding of over 50 alkyl-bearing derivatives, there is a good correlation of pKd for Hp-P-CD with that for P-CD, with unit slope. These observations imply that the binding of simple aliphatic guests to Hp-P-CD is not greatly influenced by the modification of the hydroxyl groups on the primary side of the P-CD cavity but this may not be true for longer aliphatic derivatives (>Cx) or for aromatics that penetrate farther into the CD cavity.

Role of Hydrophobic Effect on the Noncovalent Interactions Between Salicylic Acid and a Series of β-Cyclodextrins

“…Since the medium is an hydroalcoholic solution, the possible encapsulation of the alcohol molecule by the cyclodextrin, in competition with the CD:drug complex formation, must be considered. However, the K CD:Alcohol values reported in the literature (13,14) for the binding of ␤-CD and/or its derivatives to the shortest alcohols, although alcohol chain length dependent, are always three orders of magnitude lower than the uncertainty of the K CD:Guest values determined here and can be clearly neglected. As a consequence, all of the effects observed in the presence of alcohols can be attributed only to a change in the solvophobic characteristics of the medium, which obviously affects the affinity of an apolar drug in binding cyclodextrin.…”

Complexation of modified cyclodextrins with hydroxylated substances in aqueous solutions. Calorimetric studies at 298 K

“…The association of alkanols from propanol up to 1-hexanol and of cyclohexanol with bCD and HPbCD has been studied previously by other authors. The association constants differ from those reported here, probably because measurements were carried out under different experimental conditions and by different techniques, namely inhibition kinetics 25 and the spectrofluorometric displacement method. [24][25][26][27][28] For the cyclic substances reported in Table 1, namely cyclohexanol, cycloheptanol and cyclooctanol, enthalpies are negative and decrease on increasing the dimensions of the cycle, while entropies pass from negative to positive.…”

“…However, it has been experimentally proved here that, whatever the experimental conditions, alkanols shorter than 1-heptanol do not associate with HPbCD, while alkanols shorter than 1-nonanol do not associate with MbCD. On the other hand, also for natural bCD the constants reported in the literature indicate an association to the shortest alkanols negligibly small [23][24][25] or zero.…”

Microwave-Assisted Protocol for Green Functionalization of Thiophenes With a Pd/β-Cyclodextrin Cross-Linked Nanocatalyst

“…On the other hand, heterogeneous reaction yields were often lower than the homogeneous reactions when using n-butylthiophene as a reagent ( Table 2, entries 8, 13, 16, 21). These results may be caused by the n-alkyl moiety's strong binding to cyclodextrins (expressed by pKd = -log K), which increases monotonically with alkyl chain length, up to about eight carbons (Tee et al, 1996); the higher stability of the nbutylthiophene-cyclodextrin complex means that the reaction proceeds more slowly. The attempt to couple deactivated aryl halides and thiophene was quite disappointing as only aryl iodides led to the desired products in the presence of the methoxy group (Table 2, entries 20, 21, 22), and the homogeneous catalyst gave higher yields.…”