Investigating the molecular and aggregated states of a drug molecule rutaecarpine using spectroscopy, microscopy, crystallography and computational studies

Abstract

The photophysical properties of a potential drug molecule rutaecarpine have been investigated in molecular as well as aggregated states. All systems have been characterized by various spectroscopic, microscopic and dynamic light scattering (DLS) techniques. The investigation has been carried out by keeping the fact in mind that hydrophobic organic molecules have a strong tendency to form aggregates in aqueous solution. A blue shift in the absorption spectrum of rutaecarpine has been observed for aggregates (compared to molecular solution) indicating the formation of H-type aggregates. The intermolecular interactions responsible for such aggregation have been further investigated through crystallographic and computational studies. It has been observed that π-π stacking interactions among the monomer units play an important role in the formation of H-type aggregates. Quantum mechanical calculations also substantiate the blue shift in the absorption that has been observed for aggregates. In the present case, enhanced emission for aggregates as compared to the molecular solution of rutaecarpine has also been observed. The observed enhanced emission upon aggregation is attributed to the decrease of the non-radiative rate constant (knr) upon aggregation. The effect of a surface active ionic liquid (SAIL), 1-dodecyl-3-methylimidazolium bromide ([C12mim]Br), on the aggregation of rutaecarpine has been investigated. Interestingly, in addition to the decrease in the particle size, a change in the morphology of the aggregates has also been observed with gradual addition of [C12mim]Br to the colloidal solution of rutaecarpine. The present study demonstrates that a SAIL can effectively be used as a medium for dissociation of colloidal aggregates and encapsulation of molecular species, which in turn would be helpful in influencing the drug activity.

Photoresponsive Self-Assembly of Surface Active Ionic Liquid

“…The self-assembled aggregates based on ionic liquids (ILs) have attracted increasing attention during the past 10 years due to their extraordinary properties, such as negligible vapor pressure, low melting point, large electrochemical window, and thermal stability. , Ionic liquids with long alkyl chains are regarded as amphiphiles named as surface active ionic liquids (SAILs), which combine the properties of ILs and surfactants. − SAILs can self-assemble into a rich variety of hierarchically complex architectures with controllable functions depending on the structure of SAILs and the composition of solution. − Based on the designability of SAILs, it will be expected to achieve the functionalization of self-assembled aggregates by tailoring the structures of SAILs.…”

Self‐Assembly of Photoresponsive Molecular Amphiphiles in Aqueous Media

“…[199] Thec o-assembly structures of worm-like micelles became slightly longer and more entangled (as shown by cryo-TEM) after 365 nm light irradiation, allowing to form as olution with ah igher viscosity.H owever,n o significant transformation of their self-assembled system was observed in studies by Yu et al [199] Self-assembly systems based on ionic liquids have attracted increasing attention due to their extraordinary properties,s uch as negligible vapor pressure,l ow melting point, and thermal stability. [200,201] Recently,b yi ntroducing photoresponsive units into an ionic liquid, e.g.,s tilbene,c innamate,a nd azobenzene,aseries of novel photoresponsive ionic liquid have been designed, [202][203][204][205] allowing for photocontrolled assembly transformations without co-assembly with other compounds. [206][207][208][209] It is noted that the photoresponsive surface active ionic liquid with azobenzene in the headgroup,i .e., amphiphile 16,s howed dualstimuli responsive and reversible transformations from vesicles to spherical micelles (Figure 19 a).…”

“…However, no significant transformation of their self‐assembled system was observed in studies by Yu et al [199] . Self‐assembly systems based on ionic liquids have attracted increasing attention due to their extraordinary properties, such as negligible vapor pressure, low melting point, and thermal stability [200, 201] . Recently, by introducing photoresponsive units into an ionic liquid, e.g., stilbene, cinnamate, and azobenzene, a series of novel photoresponsive ionic liquid have been designed, [202–205] allowing for photocontrolled assembly transformations without co‐assembly with other compounds [206–209] .…”

Advances Brought by Hydrophilic Ionic Liquids in Fields Involving Pharmaceuticals

“…This is the first step for identifying ILs as potential carrier agents in drug delivery devices. Accordingly, a large number of reports comprising ILs as solvents to be employed in the development of promising drug delivery strategies have been published in the literature, namely by IL-based micelles [ 79 , 80 , 81 , 82 ], microemulsions [ 12 , 48 , 83 , 84 , 85 ], nanoparticles [ 86 , 87 , 88 , 89 , 90 ], functionalized silica [ 91 , 92 , 93 , 94 ], and iongels [ 95 , 96 , 97 , 98 ]. These possibilities stand out as the most relevant examples for delivery approaches with ILs, as summarized in Figure 4 .…”

“…The results gathered revealed a high potential of SAILs to develop more efficient drug delivery processes. In the same line, Dandpat et al [ 81 ] investigated the aggregation and dissociation behavior of hydrophobic drugs, namely rutaecarpine, in the presence of [C 12 C 1 im]Br by using spectroscopic, microscopic, and crystallographic analysis. The authors found that drug aggregation decreases in solution with the gradual addition of [C 12 C 1 im]Br.…”