pH‐Responsive Interaction of Fluorogenic Antimalarial Drug Quinine with Macrocyclic Host Cucurbit[7]uril: Modulations in Photophysical and Acid‐Base Properties

Abstract

Intriguing changes in photophysical and acid-base properties of fluorogenic antimalarial drug, quinine (QN), are presented on its interaction with macrocyclic cucurbit[7]uril (CB7)host. While dicationic QNH 2 2 + form shows large enhancement in both steady state and time-resolved fluorescence, monocationic QNH + and neutral QN forms show significant reductions. The pK a (1) and pK a (2) values of the drug undergo~1 and~1.7 units of upward shifts, respectively, on its binding to CB7 host, substantiating the differential binding strengths of various prototropic forms. Whereas the QNH 2 2 + and QNH + forms undergo 1:2 (dye to CB7) inclusion complex formation, the neutral QN is suggested to form 1:1 inclusion complex with CB7.Interestingly, the observed results in the present study are substantially different and in some cases quite contrasting to the results reported in a recently published paper (Phys. Chem. Chem. Phys., 2016, 18, 30520). In the present study we could unequivocally establish that there were many serious inconsistencies in the above paper, which we could now convincingly rectify, designing appropriate experimental and sample conditions. With the intriguing modulations observed in the photophysical and acid-base properties, the quinine-CB7 system is suggested to act as an improved fluorimetric standard than the free quinine system. Additionally, the modulations have implications in drug stabilization, drug delivery, sensors and other applications.

Cucurbit[n]uril Host‐Guest Complexes of Acids, Photoacids, and Super Photoacids

“…The p K a value of 4.1 for the protonated quinoline nitrogen increases to 5.2 upon formation of the 2 : 1 complex. In a subsequent study by Pal and co‐workers, 2 : 1 host‐guest complexes for the QH 2 2+ and QH + species with CB[7] were also observed (binding the aromatic quinoline first, followed by binding of the quinuclidine moiety), with the neutral Q species suggested to form a 1 : 1 complex. They report increases in the p K 1 (quinolinium) and p K 2 (quinuclidinium) values of 1.0 and 1.7 units, respectively.…”

Interaction of a Triaryl Methane Dye with Cucurbit[7]uril and Bovine Serum Albumin: A Perspective of Cooperative versus Competitive Bindings

“…To be mentioned here that for the present host‐guest systems we also carried out Job's plot measurements ( cf . Note S1 & Figure S1 in the supporting Information, SI),, and Scatchard plot analysis ( cf . Note S2 & Figure S2, SI),,,, and the results are in accordance with the 1:1 stoichiometry of the host‐guest complexes formed in the studied systems.…”

“…Due to its non‐planar and flexible structure, the excited state of CV undergoes very fast non‐radiative deexcitation process and hence the free dye is extremely weak in fluorescence . Upon binding to a macrocyclic cavity or to a biomacromolecular pocket, the dye, however, can display large enhancement in fluorescence intensity, due to large reduction in the non‐radiative deexcitation processes, caused by the imposed restriction on the flexibility of the dye molecules due to the confinement effect , In the literature CV has been emphasized as a useful dye for staining various bio‐organisms, having antifungal, antibacterial, anthelmintic and antiparasitic properties and being effective in photodynamic therapy ,…”

Stimuli Responsive Confinement of a Molecular Rotor Based BODIPY Dye inside a Cucurbit[7]uril Nanocavity

“…Engineering host–guest assemblies through stimuli responsive noncovalent interactions is the major strategy in supramolecular chemistry having applications in diverse areas. Different noncovalent interactions can uniquely participate between host and guest molecules resulting in supramolecular assemblies of intriguing architectures, large stability, repeatability, sensitivity, and many other interesting properties. − Host–guest complexation can significantly modify the properties of chromophoric guest dyes, reflected often with increased fluorescence intensity and lifetime, decreased nonradiative de-excitation, retarded rotational relaxation, increased photo- and thermal stability, altered prototropic behavior, and so forth. − Such modulations in the guest properties have prompted many studies on various dye-host systems aiming their diverse applications in chemistry, biology, and material sciences. ,,,− The complete reversibility of the dye–host complexes in the solution phase makes them very responsive to various chemical and physical stimuli, conferring their uses in different sensing applications. ,, …”

“…Among various host systems, the noteworthy ones are cyclodextrin (CD), calix­[n]­arene (CXn), and cucurbit­[n]­uril (CBn) based macrocyclic molecules, as they show prominent complexation with many organic dyes, bringing out intriguing changes in the properties of the bound dyes. ,,, In designing a supramolecular dye–host assembly for any specific application, the selection of the dye and the macrocyclic host is a very important consideration and is decided mainly based on the availability, solubility, selectivity, sensitivity, binding strength, cost effectiveness, etc. Among different hosts, the CBn based macrocyclic molecules have attracted immense interests in recent years, as they display relatively better binding affinity with most organic dyes, as compared to the other classes of the macrocyclic hosts. − …”