Probing the Structural Determinants of Amino Acid Recognition: X-Ray Studies of Crystalline Ditopic Host-Guest Complexes of the Positively Charged Amino Acids, Arg, Lys, and His with a Cavitand Molecule

Abstract

Crystallization of tetraphosphonate cavitand Tiiii[H, CH3, CH3] in the presence of positively charged amino acids, namely arginine, lysine, or histidine, afforded host-guest complex structures. The X-ray structure determination revealed that in all three structures, the fully protonated form of the amino acid is ditopically complexed by two tetraphosphonate cavitand molecules. Guanidinium, ammonium, and imidazolium cationic groups of the amino acid side chain are hosted in the cavity of a phosphonate receptor, and are held in place by specific hydrogen bonding interactions with the P=O groups of the cavitand molecule. In all three structures, the positively charged α-ammonium groups form H-bonds with the P=O groups, and with a water molecule hosted in the cavity of a second tetraphosphonate molecule. Furthermore, water-assisted dimerization was observed for the cavitand/histidine ditopic complex. In this 4:2 supramolecular complex, a bridged water molecule is held by two carboxylic acid groups of the dimerized amino acid. The structural information obtained on the geometrical constrains necessary for the possible encapsulation of the amino acids are important for the rational design of devices for analytical and medical applications.

Selective Recognition of Amino Acids and Peptides by Small Supramolecular Receptors

“…These constitute a class of receptors that present a “enforced cavity” where a small guest can bind, being the most widely studied ones those based on resorcinarenes macrocycles [ 62 , 112 ]. The Dalcanale group has reported several cavitand derivatives ( Figure 11 ) that were found to recognize amino acids and amino acid metabolites [ 113 , 114 ], and were able to obtain the crystallographic structure of the complexes between some of these cavitand receptors and all basic amino acids, Arg, Lys, and His. The 1:2 complexes were shown to be mainly stabilized by direct and water-mediated hydrogen bonds between a guest molecule and two host molecules [ 114 ].…”

Atomic Details of Carbon-Based Nanomolecules Interacting with Proteins

“…[53]. For these classes of organic molecules, besides aromatic residues hydrophilic and charged residues like arginine, lysine is important for protein-nanomolecule interactions [54][55][56].…”

Thermodynamic Characterization of the Interaction between the Antimicrobial Drug Sulfamethazine and Two Selected Cyclodextrins

“…Formation of host-guest type inclusion complexes typically occurs when the host molecule uses its cavity to encapsulate a guest through noncovalent interactions. According to the significant practical utility of macrocyclic molecules, such as calixarenes [1,2], cavitands [3,4], and cyclodextrins (CDs) [5,6] in host-guest complex formations, chemists, biologists, and material scientists got interested the physical properties, chemical nature, and related biological activity of these molecules. However, utilization of these noncovalent interactions (hydrogen-bonding, π-stacking, electrostatic interaction, van der Waals force, and hydrophobic/hydrophilic attraction) are still a great challenge [7][8][9][10].…”