Metal-Assisted Complexation of Fluorogenic Dyes by Cucurbit[7]uril and Cucurbit[8]uril: A DFT Evaluation of the Key Factors Governing the Host–Guest Recognition

Abstract

With the emergence of host-guest systems, a novel branch of complexation chemistry has found wide application in industries such as food, pharmacy, medicine, environmental protection and cosmetics. Along with the extensively studied cyclodextrins and calixarenes, the innovative cucurbiturils (CB) have enjoyed increased popularity among the scientific community as they possess even better qualities as cavitands as compared to the former molecules. Moreover, their complexation abilities could further be enhanced with the assistance of metal cations, which can interestingly exert a dual effect on the complexation process: either by competitively binding to the host entity or cooperatively associating with the CB@guest structures. In our previous work, two metal species (Mg2+ and Ga3+) have been found to bind to CB molecules in the strongest fashion upon the formation of host–guest complexes. The current study focuses on their role in the complex formation with three dye molecules: thiazole orange, neutral red, and thioflavin T. Various key factors influencing the process have been recognized, such as pH and the dielectric constant of the medium, the cavity size of the host, Mn+ charge, and the presence/absence of hydration shell around the metal cation. A well-calibrated DFT methodology, solidly based and validated and presented in the literature experimental data, is applied. The obtained results shed new light on several aspects of the cucurbituril complexation chemistry.

N-Methyl- and N-Phenylpiperazine Functionalized Styryl Dyes Inside Cucurbiturils: Theoretical Assessment of the Factors Governing the Host–Guest Recognition

“…[35], adds about 3.1 kcal mol −1 to the energy gained: the calculated ∆G ε values for the formation of both complexes CB[7]@ dye9 ^+/2+ become −10.0/−9.2 kcal mol −1 (See Figure 5B). This result is consistent with earlier observations [46,47], suggesting that the hydration of the host is beneficial for the incorporation of metal ions and/or dye guests.…”

“…The presented study aims at disclosing factors of high importance that play a key role in the modeled reactions of encapsulation such as the cavity volume, pH, and dielectric constant of the medium, presence of metal cations in the reaction medium, and specific chemical characteristics of different substituents in the dye molecule. The previously implemented well-tested DFT procedure [45][46][47][48][49] provides clear trends and reliable results in agreement with published experimental data.…”

“…The calculations were performed through the utilization of the Gaussian 09 suite of programs [63]. The most appropriate combination of a method and basis set was found to be the Minnesota functional M062X [64] with the double zeta 6-31G(d,p) basis set applied, and proven to be reliable in our previous investigations of the physicochemical properties of cucurbiturils [45][46][47]49,65]. Initial geometries of the host molecules were derived from TUHGAG (CB [7]) and BATWEA (CB [8]) entries deposited in the Cambridge Crystallographic Data Centre (CCSD) [66,67].…”

Stabilization of Guest Molecules inside Cation‐Lidded Cucurbiturils Reveals that Hydration of Receptor Sites Can Impede Binding

“…Atomistically precise structural representations of cucurbiturils lidded (capped) with alkali metal ion are available from a wealth of crystallographic data. Although the geometries in aqueous solution are necessarily more dynamic, the binding patterns to the carbonyl portals should be closely related [1f,8c–d,9c,11,29] . Crystal structures of CB5 (and CB5 ⋅ gas complexes) in the absence of metal ions contain crystal water at the carbonyl portals [28a,29] …”

Theoretical Assessment of the Ligand/Metal/Quadruplex Recognition in the Non-Canonical Nucleic Acids Structures

“…Furthermore, we evaluate the possible stacking of the most active (lowest IC 50 ) 2-quinolinyl-quinazoline derivative reported previously in [ 37 ] to the modeled tetrads. The results are obtained by utilizing a well-studied and validated DFT methodology that has proven extensively reliable when the system under study contains competing metal cofactors which bind to biological or biomimetic molecules through mostly electrostatic interactions [ 38 , 39 , 40 , 41 , 42 ]. Thus, we aim to contribute to the understanding of the underlying processes in quadruplex stabilization and its further complexation to drug molecules.…”