Glucosylthioureidocalix[4]arenes: Synthesis, conformations and gas phase recognition of amino acids

Abstract

The gas-phase recognition of native amino acids and the conformational properties of three glucosylthioureidocalix[4]arenes () were studied theoretically and experimentally using ab initio calculations, ESI-FTICR,(1)H and (13)C NMR MS. The conformational and complexation properties of the glucocalixarenes were dependent on the number of glucose units at the upper rim and the length of the alkyl chains at the lower rim of the calixarene skeleton. ESI-MS experiments showed the compounds to form 1 : 1 complexes with the amino acids, with a marked preference for amino acids containing an aromatic nucleus and an additional H-bonding group in their side chain (Trp, Tyr, Phe >> Ser, Leu and Asp). The experimental data were rationalized by the results of ab initio calculations. ESI-MS competitions carried out with enantiomeric-labelled (EL) amino acids showed enantiomeric selectivities ranging from 0.61 (Phe(D)/Phe(L) with ligand ) to 2.58 (Tyr(D)/Tyr(L) with ligand ). In gas-phase hydrogen-deuterium (H/D) exchange reactions, diglucosylcalix[4]arene exhibited extremely slow exchange rates, which were attributed to the close proximity and strong hydrogen bonding between the facing glucosylthioureido groups. H/D exchange rates were much higher for the tetraglucosylcalix[4]arenes and and their amino acid complexes, and the more rigid tetrapropoxy derivative showed more selective H/D exchange reactions than the calixarene . Bi- or trimodal H/D exchange distribution was observed for the tetraglucosyl derivatives indicating that these ligands exist in multiple isomeric forms in gas phase.

Noncovalent Complexation of Monoamine Neurotransmitters and Related Ammonium Ions by Tetramethoxy Tetraglucosylcalix[4]arene

“…With ND 3 as the reagent gas, protonated 1 ([1+H] + ) exhibited a bimodal exchange distribution ( Figure 5, top), most likely due to co-existing gas-phase conformers of 1 that react with clearly different rates [63][64][65]. This behavior is consistent with the results of our earlier study [52].…”

“…(3) The selectivity shown for the serotonin (9) confirmed the preference of glucosylcalixarene for guests bearing indole nuclei. The same was observed earlier in the complexation of tryptophan by 1 [52].…”

“…Possible cooperation between the aromatic cavity, thiourea linkers, and sugar units of glucosylcalixarenes in the guest binding has been indicated in these studies [57]. Clear selectivity towards aromatic amino acids has also been observed, and enhanced by the introduction of an additional hydrogen bonding group to the amino acid side chain [52]. The proximity of the hydrogen bonding groups of the guest also has a major effect on the selectivity of the complexation [58].…”

“…Series of thiourea-linked calix [4]arene glycoclusters [50][51][52] have been synthesized and their interactions with proteins [53][54][55][56][57], anionic species [57], natural amino acids [52], and carboxylates [58] investigated. Possible cooperation between the aromatic cavity, thiourea linkers, and sugar units of glucosylcalixarenes in the guest binding has been indicated in these studies [57].…”

Functionalization reactions of calixarenes

“…Many calixarenes functionalized at the wide rim are known, [81][82][83][84][85][86] It should be noted that functionalization of the wide rim is more difficult than of the narrow rim. Functionalization of the wide rim requires protection of the narrow rim hydroxyl groups and also removal of the t-butyl groups from the wide rim.…”