J. Vázquez Tato

Complexation of 6-Deoxy-6-(aminoethyl)amino-β-cyclodextrin with Sodium Cholate and Sodium Deoxycholate

In order to study its guest binding and the inclusion phenomena, 6-deoxy-6-(aminoethyl)amino-β-cyclodextrin (βCDN) was synthesised and its binding properties examined. The complexation phenomena of sodium cholate (NaC) and sodium deoxycholate (NaDC) with βCDN has been monitored by the NMR method using 13C chemical shift data. The method of continuous variation ’“Jobs method” has been used to determine the stoichiometry of these supramolecular complexes. The Jobs plot confirms the 1 : 1 supramolecular complex for NaC: βCDN and the 1 : 2 supramolecular complex for NaDC: βCDN. The interaction of NaC and NaDC with βCDN has been obtained through two-dimensional Rotational Nuclear Overhauser Effect Spectroscopy (ROESY) NMR. Equilibrium constants were also obtained from 13C chemical shift data (C-1, C-3 & C-4) at different pH values (7, 9, & 11).

Successful prediction of the hydrogen bond network of the 3-oxo-12α-hydroxy-5β-cholan-24-oic acid crystal from resolution of the crystal structure of deoxycholic acid and its three 3,12-dihydroxy epimers

Crystal structures of p-xylene-crystallized deoxycholic acid (3alpha,12alpha-dihydroxy-5beta-cholan-24-oic acid) and its three epimers (3beta,12alpha-; 3alpha,12beta-; and 3beta,12beta-) have been solved. Deoxycholic acid forms a crystalline (P21) complex with the solvent with a 2:1 stoichiometry whereas crystals of the three epimers do not form inclusion compounds. Crystals of the 3beta,12beta-epimer are hexagonal, whereas the 3alpha,12beta-and 3beta,12alpha-epimers crystallize in the P2(1)2(1)2(1) orthorhombic space group. The three hydrogen bond sites (two hydroxy groups, i. e. O3-H, and O12-H, and the carboxylic acid group of the side chain, O24bO24a-H) simultaneously act as hydrogen bond donors and acceptors. The hydrogen bond network in the crystals was analyzed and the following sequences have been observed: two chains (abcabc... or acbacb... ) and two rings (abc or acb), which constitute a complete set of all the possible sequences which can be drawn for an intermolecular hydrogen bond network formed by three hydrogen bond donor/acceptor sites forming crossing hydrogen bonds. The orientation of O3-H (alpha or beta) determines the sequence of the acceptor and the donor groups involved in the pattern: O24a --> O12 --> O3 --> O24b when it is alpha and O24a --> O3 --> O12--> O24B when it is beta. These observations were used to predict the hydrogen bond network of p-xylene-crystallized 3-oxo,12alpha-hydroxy-5beta-cholan-24-oic acid. This compound has two hydrogen bond donor and three potential hydrogen bond acceptor sites. According to the previous sequence set, this compound should crystallize in the monoclinic P21 system, should form a complex with the solvent, O24b should not participate in the hydrogen bond network, and the chain sequence O24a --> O12 --> O3 would be followed. All predictions were confirmed experimentally.

Inhibition by Cyclodextrins of Nitrosation Reactions

Nitrite esters (RONO) are effective nitrosating reagents in aqueous basic media.1-5 Previous studies5 of their reaction with different alifatic and heterocyclic secondary amines, to yield N-nitrosoamines, have shown that the following rate equation

Complexation of Sodium Cholate and Sodium Deoxycholate by β-Cyclodextrin and Derivatives†

v = k_2 [{\text{amine}}][RONO]/(1 + [H^ + ]/K_1 )

Aggregation Number for Sodium Deoxycholate from Steady-State and Time-Resolved Fluorescence

(1) is obeyed. It suggests that the rate limiting step is the attack of the nitrite ester on the free amine.

Unusual Pyrene Excimer Formation during Sodium Deoxycholate Gelation

Cyclodextrins are known to form inclusion complexes with a variety of molecules, a property used to increase the bioavailability of poorly soluble drugs1. Bile salts are biosurfactants involved in the cholesterol metabolism, and used as drugs in gallstone diseases treatments2.