Melatonin-directed micellization: a case for tryptophan metabolites and their classical bioisosteres as templates for the self-assembly of bipyridinium-based supramolecular amphiphiles in water

Abstract

The bulk solution properties of amphiphilic formulations are derivative of their self-assembly into higher ordered supramolecular assemblies known as micelles and of their ordering at the air-water interface. Exerting control over the surface-active properties of amphiphiles and their propensity to aggregate in pure water is most often fine-tuned by covalent modification of their molecular structure. Nevertheless structural constraints which limit the performance of amphiphiles do emerge when trying to develop more sophisticated systems which undergo for example, shape-defined controlled assembly and/or respond to external stimuli. In this regard, the template-modulated assembly of the so-called "supramolecular amphiphiles" continues to make progress ordering molecules that otherwise have very little to no driving force to aggregate in a prescribed manner in aqueous solutions. Herein we describe the template-modulated micellization and ordering at the air-water interface of bipyridinium-based supramolecular amphiphiles triggered by host-guest interactions with high specificity for the neurotransmitter melatonin over its biosynthetic synthon l-tryptophan and the thermodynamic parameters governing the template-modulated micellization process. When bound to the bipyridinium units of micellized surfactant molecules, melatonin effectively serves as "molecular glue" capable of lowering the CMC by 52% as compared to untemplated solutions. Analysis of this system suggests that a hallmark of donor-acceptor template-modulated micellization in water is a strong positively correlated temperature dependence of the CMC and the absence of a U-shaped CMC-temperature curve. Our findings make a case for the incorporation of l-tryptophan-based metabolites and their classical synthetic pharmaceutical bioisosteres as potential targets/components of donor-acceptor CT-based supramolecular amphiphile systems/materials operating in water.

The Unusual Photochromic and Hydrochromic Switching Behavior of Cellulose‐Embedded 1,8‐Naphthalimide‐Viologen Derivatives in the Solid‐State

“…Upon further analysis, the substantial spectral overlap of the absorption spectrum for the viologen radical cation and the emission spectrum for the naphthalimide fluorophore cannot be ignored and is the most likely source of the fluorescence quenching [42] . A similar emission quenching effect was induced (Figure S31) for dyad 3C ⋅ 2Br, when it was combined with 1 mole equivalent of the π‐electron rich donor, melatonin, and formed a π‐stacked charge transfer complex with the π‐electron deficient viologen moeity [10e] . In this case, the π→π* charge transfer absorption band for the complex also substantially overlapped the emission spectrum of the naphthalimide fluorophore, resulting in emission quenching.…”

Poly-Lipoic Ester-Based Coacervates for the Efficient Removal of Organic Pollutants from Water and Increased Point-of-Use Versatility

“…Both melatonin and L-tryptophan are strongly πelectron-donating and capable of forming DA charge transfer complexes with bipyridinium derivatives in water. 86−88 However, as previously reported, 89 their differential binding constants for complex formation with bipyridinium-based amphiphiles in water is driven by the strength of their hydrophobic interactions. Here, we also find that pollutant selectivity is not based on its π-electron-donating ability but rather on the hydrophobicity and solubility of the molecular target.…”

Bis‐Bipyridinium Gemini Surfactant‐Based Supramolecular Helical Fibers and Solid State Thermochromism

“…The solid‐state thermochromism of these materials was the result of competing donor–acceptor CT interactions . The color of the donor–acceptor complex at room temperature is derived from the π→π* CT interactions between the two organic components of the complex, namely the π‐electron‐rich donor, melatonin, and the tetracationic π‐electron‐deficient bis‐bipyridinium acceptor . At elevated temperatures, the color of these materials is derived from the n →π* CT interactions between the acceptor and its halogen counterions .…”

“…Starting materials and reagents were purchased from Tokyo Chemical Industry and used as received. 1,4‐dibromo‐methylnaphthalene, 1,5‐dibromo‐methylnaphthalene, and mono‐undecylated bipyridine were synthesized following procedures reported in the literature. All reactions were performed under an argon atmosphere and in dry solvents, unless otherwise noted.…”