Simulations on the possibility of formation of complexes between fluorouracil drug and cucurbit[n]urils: ab initio van der Waals DFT study

Abstract

The binding geometry of fluorouracil/cucurbit[n]urils (CB[n]s) complexes with n = 5-8 is investigated using the first-principles van der Waals density functional (vdW-DF) method, involving full geometry optimization. Such host-guest complexes are typically calculated using conventional DFT method, which significantly underestimates non-local dispersion forces (or vdW contributions) and therefore affects interactions between respected entities. We address here the role of vdW forces for the fluorouracil and CB[n]s molecules which can form directional hydrogen bonds with each other. It was found that the inclusion of dispersion interactions significantly affects the host-guest binding properties and the hydrogen bonding between the molecules provides the main binding mechanism, while results in the same geometries for the considered complexes. The 0.84 eV binding energy, for the thermodynamically favorable state, reveals that the interaction of fluorouracil with CB[n]s is an exothermic interaction and typical for strong hydrogen bonding. Furthermore, we have investigated the binding nature of these host-guest systems in aqueous solution with ab initio MD simulations adopting vdW-DF method. These findings afford evidence for the applicability of the vdW-DF approach and provide a realistic benchmark for the investigation of the host-guest complexes.

Pristine and alkali and alkaline earth metals encapsulated B36N36 nanoclusters as prospective delivery agents and detectors for 5‐fluorouracil anticancer drug

“…45 Fayyaz et al [65] Sumanene B3LYP-D3 À17.14 Reichert et al [64] Cucurbit [6]urils PBE-D À19. 37 Sabet and Ganji [61] Zn 12 O 12 B3LYP À18. 41 Zhihong et al [14] Boron carbide nanotube M06-2X À21.…”

“…There are indeed several theoretical reports on the interactions of the FU molecule with different nano‐based materials. [ 59–69 ]…”

“…There are indeed several theoretical reports on the interactions of the FU molecule with different nano-based materials. [59][60][61][62][63][64][65][66][67][68][69] In this context, we attempt in the present research to investigate the interactions of FU molecule with the B 36 N 36 nanocluster. The evaluation of this process is important to understand and predict the role of nanoclusters as drug delivery systems.…”

Piperine Encapsulation within Cucurbit[n]uril (n=6,7): A Combined Experimental and Density Functional Study

“…To understand the nature of the interaction between the guest and host cucurbiturils, several theoretical studies have been done . It has been suggested that the nature of interactions between the guest and host cucurbituril are dominated by (i) charge‐dipole interactions, when a cationic host is used (ii) hydrogen bonding interactions between the guest's hydrogen atoms with the carbonyl portal of the host (iii) hydrophobic interactions which exits at the concave cavity of the cucurbituril and (iv) hydrogen interactions between the hydrogen atoms of methylene unit of cucurbituril with guest molecules or an interplay of the above interactions .…”

Ligand binding constants of the cucurbit[7]uril predicted with molecular docking: a theoretical study

“…the dispersion interaction dramatically affects, as compared to the PBE based calculations, the binding of the host-guest complexes and is crucial to describe such systems". 12 Gavvala et al investigated the interaction of the cardiotonic drug, milrinone, binding in the CB7 molecule with molecular docking (AutoDock software) and optimized the host-guest complex structure with a semiempirical (PM3MM) method. 13 The field of CB7 host-guest chemistry became very exciting recently; many authors pointed out the essence of the "high energy" cavity waters and the importance of other above mentioned interactions during hostguest complex formation.…”