José A. Moreira

Supramolecular Catalysis by Cucurbit[7]uril and Cyclodextrins: Similarity and Differences

To understand the analogies and differences between the cucurbituril and cyclodextrin cavities different solvolytic reactions have been studied in the presence of cucurbit[7]uril, CB7, and beta-CD or its methylated derivative, DM-beta-CD. Solvolysis of 1-bromoadamantane has been used as a test to evaluate the ability of the cavities to solvate the Br(-) leaving group. Obtained results show that in both cases the polarity inside the cavity is similar to that of a 70% ethanol:water mixture. Solvolysis of substituted benzoyl chlorides shows a great difference between the CB7 and DM-beta-CD cavity. Solvolysis of electron withdrawing substituted benzoyl chlorides (associative mechanism) is catalyzed by DM-beta-CD and inhibited by CB7. However, solvolysis of electron donating substituted benzoyl chlorides (dissociative mechanism) is catalyzed by CB7 and inhibited by DM-beta-CD. These experimental behaviors have been explained on the basis of different solvolytic mechanisms. Participation of the hydroxyl groups of the cyclodextrin as a nucleophile can explain the catalytic effect observed for solvolysis of benzoyl chlorides reacting by an associative mechanism. Solvolysis of benzoyl chlorides reacting by a dissociative mechanism is catalyzed by CB7 due to the ability of the CB7 cavity to stabilize the acylium ion developed in the transition state by electrostatic interactions.

Evidence of Higher Complexes Between Cucurbit[7]uril and Cationic Surfactants

The host-guest assembly of CB7 with a series of alkyl(trimethyl)ammonium (C(n)TA(+)) surfactants of different chain lengths (n=6-18) has been studied. The complexation behaviour was investigated by NMR spectroscopy, isothermal titration calorimetry and kinetics measurements. The combined results of these techniques provided evidence for the formation of 1:1 inclusion and 2:1 external complexes in the cases of C(n)TA(+) with n=12-18. The binding constants for the 1:1 complexes are independent of the alkyl chain length of the surfactant, whereas a relationship between K(2:1) and the chain length of the surfactant was found for the 2:1 complexes.

Cucurbit[7]uril: surfactant host-guest complexes in equilibrium with micellar aggregates.

In order to compare the formation of host-guest complexes between β-cyclodextrin (β-CD) or cucurbit[7]uril (CB7) and cationic surfactants we studied the hydrolysis of 4-methoxybenzenesulfonyl chloride (MBSC). The selected surfactants allowed the length of the hydrocarbon chain to be varied between 6 and 18 carbon atoms. Contrary to the expected behaviour, the values of the binding constants between CB7 and surfactants are independent of the alkyl chain length of the surfactant. In the case of β-CD, however, a clear dependence of the binding constant on the hydrophobic character of the surfactant was observed. The values obtained with CB7 are significantly higher than those obtained with β-CD and these differences are explained to be a consequence of electrostatic interactions of the surfactants with the portals of CB7. It was found that a small percentage of uncomplexed CB7 was in equilibrium with the cationic micelles and this percentage increased on increasing the hydrophobic character of the surfactant.

Electrostatic repulsion between cucurbit[7]urils can be overcome in [3]pseudorotaxane without adding salts.

The host-guest chemistry between cucurbit[7]uril (CB7) and a series of bolaform (Bn) surfactants with different chain lengths, n = 12-22, was the target of our study. [3]Pseudorotaxanes are formed when the alkyl chain of the bolaform has more than 14 carbon atoms. In these cases, two CB7 molecules can be accommodated between the two head groups of the bolaform without addition of electrolytes to the medium. In the case of a bolaform with 12 carbon atoms, the electrostatic repulsion between the carbonyl groups of the CB7 molecules avoids the threading of a second CB7 molecule yielding a mixed structure formed by a [2]pseudorotaxane and an external host-guest complex. The assembly behavior was investigated using NMR spectroscopy, isothermal titration calorimetry (ITC), and kinetic measurements.

Importance of phenols structure on their activity as antinitrosating agents: A kinetic study.

Objective: Nitrosative deamination of DNA bases induced by reaction with reactive nitrogen species (RNS) has been pointed out as a probable cause of mutagenesis. (Poly)phenols, present in many food items from the Mediterranean diet, are believed to possess antinitrosating properties due to their RNS scavenging ability, which seems to be related to their structure. It has been suggested that phenolic compounds will react with the above-mentioned species more rapidly than most amino compounds, thus preventing direct nitrosation of the DNA bases and their transnitrosation from endogenous N-nitroso compounds, or most likely from the transient N-nitrosocompounds formed in vivo. Materials and Methods: In order to prove that assumption, a kinetic study of the nitroso group transfer from a N-methyl-N-nitrosobenzenesulfonamide (N-methyl-N-nitroso-4-methylbenzenesulfonamide, MeNMBS) to the DNA bases bearing an amine group and to a series of phenols was carried out. In the transnitrosation of phenols, the formation of nitrosophenol was monitored by Ultraviolet (UV) / Visible spectroscopy, and in the reactions of the DNA bases, the consumption of MeNMBS was followed by high performance liquid chromatography (HPLC). Results: The results obtained point to the transnitrosation of DNA bases being negligible, as well as that of phenols bearing electron-withdrawing groups. Phenols with methoxy substituents in positions 2, 4, and / or 6, although they seemed to react, did not afford the expected product. Phenols with electron-releasing substituents, unless these blocked the oxygen atom, reacted with our model compound at an appreciable rate. O-nitrosation of the phenolate ion followed by rearrangement of the C-nitrosophenol seemed to be involved. Conclusion: This study provided evidence that the above compounds might actually act as antinitrosating agents in vivo.

Kinetic study of an autocatalytic reaction: nitrosation of formamidine disulfide

The reaction kinetics for the acid nitrosation of formamidine disulfide (FDS) show an autocatalytic behavior that arises from the fact that the thiocyanate ion formed as a product acts as a powerful catalyst for the nitrosation reaction. In the presence of added nucleophiles the suppression of the autocatalytic route results from competition for the nitrous acid between the added halides and the thiocyanate anion, which is formed as a reaction product. Analysis of the kinetic data enabled extraction of the bimolecular rate constants, kNO+ = (3.2 ± 1.8) × 1010 M−1 s−1; kNOSCN = (2.1 ± 0.2) × 105 M−1 s−1; kNOBr = (9.4 ± 0.2) × 106 M−1 s1 and kNOCl = (4.0 ± 0.2) × 107 M−1 s−1, for the pathways catalyzed by SCN−, Br− and Cl−, respectively. Kinetic results are consistent with the attack on the nitrosating agent as the rate limiting step, i.e., the nitrosation of FDS behaves in a similar manner to the nitrosation of an amine. Rather different behavior is found for other substrates with an imino moiety adjacent to an amino nitrogen, such as the guanidines, which react by a mechanism in which the rate limiting step is the reorganization of the nitrosated substrate.

Kinetics and mechanism of nitrosation of clonidine: a bridge between nitrosation of amines and ureas

Nitrosation of clonidine has been studied kinetically both in acid medium (with nitrous acid) and in basic medium (with 2,2-dichloroethyl nitrite). The reactive form in acid medium was found to be the protonated clonidine (pKa 8.18). The absence of catalysis by halides or thiocyanate, the existence of general base catalysis, and the measured solvent isotope effect all indicate that the reaction mechanism is different from that for the N-nitrosation of amines. Specifically, kinetic results indicate that the attack of the nitrosating agent on the substrate is not the rate determining step of the process, and suggest a mechanism that shows parallels with that found for ureas. However, in slightly basic medium, the reaction of clonidine with the alkyl nitrite occurs through the free base form of clonidine, as shown by the influence of acidity upon the reaction rate. In this case, the kinetic behaviour is similar to that exhibited by amines.

Equilibrium constants and protonation site for N-methylbenzenesulfonamides

Summary The protonation equilibria of four substituted N-methylbenzenesulfonamides, X-MBS: X = 4-MeO (3a), 4-Me (3b), 4-Cl (3c) and 4-NO2 (3d), in aqueous sulfuric acid were studied at 25 °C by UV–vis spectroscopy. As expected, the values for the acidity constants are highly dependent on the electron-donor character of the substituent (the pK BH+ values are −3.5 ± 0.2, −4.2 ± 0.2, −5.2 ± 0.3 and −6.0 ± 0.3 for 3a, 3b, 3c and 3d, respectively). The solvation parameter m* is always higher than 0.5 and points to a decrease in the importance of solvation on the cation stabilization as the electron-donor character of the substituent increases. Hammett plots of the equilibrium constants showed a better correlation with the σ+ substituent parameter than with σ, which indicates that the initial protonation site is the oxygen atom of the sulfonyl group.

Kinetics and mechanism of acid hydrolysis of 1-methyl-1-nitroso-3-p-tolylsulfonylguanidine and 1-methyl-1-nitroso-3-benzoylguanidine

Kinetics of acid hydrolysis of 1-methyl-1-nitroso-3-p-tolylsulfonylguanidine 2 and of two 1-methyl-1-nitroso-3-benzoylguanidines (4-unsubstituted and 4-chloro) 5 and 6 have been studied. For the acid hydrolysis of 1-methyl-1-nitroso-3-p-tolylsulfonylguanidine 2, the absence of catalysis by thiocyanate ion, and the value of the kinetic solvent isotope effect indicate that either a rate determining proton transfer followed by fast denitrosation or a concerted pathway is involved in the mechanism. In the case of the acid hydrolysis of 1-methyl-1-nitroso-3-benzoylguanidines 5 and 6 it was observed that the protonated form decomposes via two parallel pathways. One involves a slow nucleophilic attack concerted with an intramolecular proton transfer, and the other a slow concerted denitrosation, where a second proton transfer and NO+ expulsion are simultaneous.

Nitrosation of N-Methyl-4-tolylsulfonylguanidine†

Kinetic studies for the nitrosation of N-methyl-4-tolylsulfonylguanidine identify a mechanism involving rapid nitrosation of the N-methyl nitrogen atom followed by slow, general-base-catalysed proton transfer.