Organic ligand-receptor interactions between cucurbituril and alkylammonium ions

Abstract

Experimental binding energies for 24 substituted ammonium ion ligands for the synthetic receptor cucurbituril are adjusted for ligand solvation and then are factored by regression analysis into contributions from various fragments of the ligands in their inclusion complexes. This allows quantitative estimation of noncovalent forces occurring in the interaction of ligand with receptor. It is concluded that the center of cucurbituril constitutes a lipophilic region but that the entrances to the interior (ammonium ion binding site) are countervailingly lipophobic. Enhanced dispersion forces involving the thioether functional group may exist in the receptor complexes of such ligands, but they make no extra contribution to the hydrophobic effect generally. The specificity of cucurbituril as a molecular receptor is explained in terms of ion-dipole attractions and shape complementarity with ligands.The phenomenon of noncovalent bonding is a topic of major significance to investigators of interactions between biological molecules. The weak intrinsic affinities between nonpolar moieties in aqueous solution are thought to be responsible for the aggregation of lipids, and in many instances for the binding of enzyme substrates, inhibitors, hormones, antigens, etc. to their receptor sites. These noncovalent forces involving small molecules are sufficiently weak that as a practical matter they can only be studied when their effects are cumulative. In this regard the recent availability of synthetic molecular ligand-receptor systems introduces major opportunities for systematic chemical investigation of this important, but ill-understood topic.Cucurbituril (Figure 1) is a novel nonadecacyclic cage compound of hexagonal symmetry, which is readily assembled by

Bindungsmechanismen in supramolekularen Komplexen

“…B. aus der Abfolge der Stabilitäten mit n-Pentan-Derivaten hervorgeht (Schema S9). [239] Die Bindungsenthalpien bestimmen die Affinitätsunterschiede. Die stabilitätsmindern-den TDS-Beiträge unterscheiden sich dagegen weniger und sind unter Umständen sogar kleiner bei den stärkeren Komplexen.…”

Ligand Migration in the Gaseous Insulin-CB7 Complex—A Cautionary Tale About the Use of ECD-MS for Ligand Binding Site Determination

“…It is evident that this is not directly translated to the gas phase from the ESI mass spectrum shown in Figure 2, which shows that only~90 % of insulin exists in complex with CB7. This could be a result of using ammonium acetate buffer in our studies in place of sodium phosphate buffer, given that ammonium ions have a strong affinity for CB7 [32,33], or it could suggest that some complexes are falling apart in the ESI mass spectrometry process. At higher concentrations of CB7 ligand (100 μM) and bovine insulin (50 μM) there was a small amount (~5 %) of signal intensity from the 1:2 complex (data not shown), which could be a result of non-specific binding at higher concentrations.…”

Cucurbiturilas

“…A basicidade destes compostos é bastante baixa sendo verificados pKa's do ácido conjugado do CB [6] da ordem de 3, sendo desconhecida para os outros cucurbitandos. Uma das estratégias para contornar o problema de solubilidade é a utilização de meios salinos ou ácidos para aumentar a solubilidade destes compostos pela formação de complexos com ácidos duros ou, ainda, pela protonação das carbonilas dos opérculos destas estruturas 12 4,7,[16][17][18][19][20][21][22][23][24][25][26][27] . A reação de CB [6], por exemplo com K 2 S 2 O 8 , dá origem a 12 grupos OH radiais nos carbonos terciários em meio aquoso 22,28 , enquanto que a utilização de dimetil glicolurila como monômero precursor dá origem à decametil-CB [5] …”

“…Desta forma, os cucurbitandos são capazes de formar compostos de inclusão, complexos e adutos com uma enorme variedade de espécies quí-micas 35,36 . Podemos citar entre elas as aminas 12,14,34,[37][38][39] , compostos aromáticos 40,41 , heterocíclicos [42][43][44] , viologênios [44][45][46][47][48][49] , poliaminas, peptídios e aminoácidos [50][51][52] , álcoóis 50,53,54 , surfatantes 53,55 , tióis, gases como CO 2 , O 2 , Kr, N 2 e Xe 31,32,56-58 , metais, complexos e muitas outras, como corantes 59,60 e fármacos [59][60][61][62] (Tabela 2). Em termos de constantes de formação médias de caviplexos de CB [6] com um grande número de compostos, como álcoóis por exemplo, são geralmente uma ordem de grandeza superiores às obtidas com α-ciclodextrinas, mostrando que também exibem uma grande afinidade por moléculas neutras, além de maior seletividade por conta dos fatores mencionados anteriormente.…”