z Organic & Supramolecular Chemistry pH-Responsive Interaction of Fluorogenic Antimalarial Drug Quinine with Macrocyclic Host Cucurbit[7]uril: Modulations in Photophysical and Acid-Base Properties Deepak R. Boraste + , [a] Goutam Chakraborty + , [b] Alok K. Ray, [b] Ganapati S. Shankarling,* [a] and Haridas Pal* [c] 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 incon- sistencies in the above paper, which we could now convinc- ingly rectify, designing appropriate experimental and sample conditions. With the intriguing modulations observed in the photophysical and acid-base properties, the quinine-CB7 sys- tem 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. Introduction Supramolecular chemistry encompasses the precisely organized structural molecular assemblies formed between constituent units via noncovalent interactions and deals with their chem- ical, physicochemical and other properties, largely different than those of the individual constituent units. [1–6] Hydrogen bonding, van der Waals forces, p-p stacking, CH-p interactions, hydrophobic and hydrophilic interactions, ion-dipole and di- pole-dipole interactions, etc. are the different interaction modes through which smaller molecular units associate with each other to form larger well-arranged supramolecular assemblies. [1–12] It is well realized in the literature that the photophysical and other chemical properties of the chromo- phoric dye molecules and/or drugs are modulated very largely on their supramolecular inclusion complex formation with macrocyclic host molecules, which can be utilized very effectively in various applied areas. [1–4,7,8,11] Enhancing fluorescence yields and lifetimes, causing large pK a shifts, inhibiting aggregation in aqueous solutions, increasing photo- stability, enhancing chemical stability, providing preferences for selective conformational structures, controlling pro-drug to drug conversion and vice versa, enhancing bio-availability of drugs, etc. are some of the noteworthy modulations favorably introduced by supramolecular host-guest interactions. [1–3, 7–16] The supramolecularly assisted modulations in the photophys- ical and other chemical properties of the dyes/drugs and their possible applications in diverse areas like fluorescent sensing, functional materials, nano-medicines, chemical sensors, cataly- sis, dye lasers, biochemical sciences, etc. [1–4, 7–23] are the prime impetus behind the extensive studies carried out on supramolecular host-guest interactions in contemporary chem- ical sciences. Cucurbit[n]uril (CBn) homologues are the relatively young but are extremely important macrocyclic host molecules in the supramolecular host-guest chemistry. [1,2,4,11,24–35] In the CBn family, the macrocyclic molecule CB7 has been most extensively used in various supramolecular studies. CB7 has reasonably good solubility (3-4 mM) in un-buffered water. [1,2,11,31,36–38] The sufficiently voluminous cavity of CB7 (279 A ˚ 3 ) can suitably encapsulate the organic chromophoric guest dyes, either partially or fully, depending upon the size and shape of the dye [a] D. R. Boraste, + Prof. G. S. Shankarling Department of Dyestuff Technology Institute of Chemical Technology Matunga, Mumbai-400019, India E-mail: gsshankarling@gmail.com [b] G. Chakraborty, + Prof. A. K. Ray Laser & Plasma Technology Division BARC, Mumbai-400085, India & Homi Bhabha National Institute Anushaktinagar, Mumbai-400094, India [c] Prof. H. Pal Radiation & Photochemistry Division BARC, Mumbai-400085, India & Homi Bhabha National Institute Anushaktinagar, Mumbai-400094, India E-mail: hpal@barc.gov.in [ + ] Both DRB and GC contributed equally in this work. Supporting information for this article is available on the WWW under https://doi.org/10.1002/slct.201700686 Full Papers DOI: 10.1002/slct.201700686 5128 ChemistrySelect 2017, 2, 5128 – 5142  2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim