Encapsulation and characterization of proton-bound amine homodimers in a water-soluble, self-assembled supramolecular host

Abstract

Cyclic amines can be encapsulated in a water-soluble selfassembled supramolecular host upon protonation. The hydrogenbonding ability of the cyclic amines, as well as the reduced degrees of rotational freedom, allows for the formation of proton-bound homodimers inside of the assembly that are otherwise not observable in aqueous solution. The generality of homodimer formation was explored with small N-alkyl aziridines, azetidines, pyrrolidines, and piperidines. Proton-bound homodimer formation is observed for N-alkylaziridines (R ‫؍‬ methyl, isopropyl, tert-butyl), Nalkylazetidines (R ‫؍‬ isopropyl, tert-butyl), and N-methylpyrrolidine. At high concentration, formation of a proton-bound homotrimer is observed in the case of N-methylaziridine. The homodimers stay intact inside the assembly over a large concentration range, thereby suggesting cooperative encapsulation. Both G3(MP2)B3 and G3B3 calculations of the proton-bound homodimers were used to investigate the enthalpy of the hydrogen bond in the protonbound homodimers and suggest that the enthalpic gain upon formation of the proton-bound homodimers may drive guest encapsulation.host-guest chemistry ͉ molecular recognition ͉ guest encapsulation ͉ amine protonation H ydrogen bonding and protonation play vital roles in both chemical and biological phenomena as one of the most prevalent intermolecular forces in nature (1-4). Although hydrogen bonding is often viewed as a weak interaction, the strength of a special class of strong hydrogen bonds, often referred to as ionic hydrogen bonds, can range from 5 to 35 kcal/mol (5). These strong hydrogen bonds are important in nucleation, self-assembly, protein folding, reactivity of enzyme active sites, formation of membranes in biological systems, and biomolecular recognition (5-7). Because of the importance of hydrogen bonding in so many aspects of chemical and biological systems, a number of synthetic and theoretical studies have examined their magnitude and origin (8, 9). Many of the computational studies have focused on simple proton-bound homodimers and heterodimers, where 2 neutral bases are bound by 1 proton (Fig. 1), because experimental energies for these complexes can be obtained from gas phase thermochemical studies such as variable-temperature high-pressure mass spectrometry (5).In simple hydrogen-bonded complexes such as those shown in Fig. 1, the hydrogen bond strength is maximized when the proton donor and the conjugate base of the proton acceptor have similar proton affinities. Therefore, the strongest hydrogen bonds are formed when the 2 basic components, minus the proton, are identical (5). Although the proton-bound homodimers and heterodimers can be observed in the gas phase, solution studies of these types of complexes remain rare. To the best of our knowledge, proton-bound homodimers or heterodimers predominantly form in aprotic organic solvents, rather than protic hydrogen-bonding solvents (5, 10).Previous work in the K.N.R. group has explored the formation, guest exchange dynamics, and mediated reac...

Supramolecular Coordination: Self-Assembly of Finite Two- and Three-Dimensional Ensembles

“…These homodimers are otherwise not obersevable in aqueous medium. 585 A wide range of cyclic amines showed a proton-bound homodimer for N -alkyl aziridines, azetidines, pyrrolidines, and piperidines. Cyclic amines were chosen as guests due to their reduced degrees of rotational freedom, which attenuates the entropic price paid for encapsulation of multiple guests.…”

Introduction to the Molecular Recognition and Self-Assembly Special Feature

“…Placing functional groups on the concave surface of a molecule is a difficult chemical manoeuver, but the article by Ballester and Gil-Ramirez (7), ''Selfassembly of dimeric tetraurea calix [4]pyrrole capsules,'' uses assembly to accomplish just that. Moreover, they do so in the much harder environment of the inner surface of a capsule.…”

“…The electronic environment inside still another capsule is explored in the contribution by Pluth et al (4), ''Encapsulation and characterization of protonbound amine homodimers in a watersoluble, self-assembled supramolecular host.'' These capsules are also held together by metal/ligand interactions that result in large overall negative charge in the shell provided by the host and stabilize positively charged guests inside.…”

“…Biology provides the vehicle and inspiration for the article by Martos et al (12), ''Calix [4]arene-based conicalshaped ligands for voltage-dependent potassium channels.'' The C 4 symmetry of potassium channels mapped neatly on a calixarene scaffold.…”

“…Moreover, they do so in the much harder environment of the inner surface of a capsule. Two calyx [4]pyrroles are stitched together with a cyclic seam of hydrogen bonds to provide the capsule. In this host, guests are presented with the hydrogen-bond donors of the pyrroles.…”