Supramolecular Enhancement of BODIPY Singlet Oxygen Generation Using Bile Salt Micelles

Research Article

Austin J Anal Pharm Chem. 2023; 10(2): 1161.

Supramolecular Enhancement of BODIPY Singlet Oxygen Generation Using Bile Salt Micelles

Sharvani Regmi1#; Ashley Maharjan1#; Vijayakumar Ramalingam2; Elamparuthi Ramasamy3; Mahesh Pattabiraman1*

1University of Nebraska Kearney, Kearney, NE – 68845, USA

2Department of Biology and Chemistry, SUNY Polytechnic Institute, Utica, NY 13502, USA

3Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, USA

*Corresponding author: Mahesh Pattabiraman University of Nebraska Kearney, Kearney, NE – 68845, USA. Email: pattabiramm2@unk.edu

#These authors have contributed equally to this article.

Received: October 04, 2023 Accepted: October 30, 2023 Published: November 06, 2023

Abstract

Singlet Oxygen (SO) generation is the core chemical process of many medical and industrial applications. Designing efficient SO-Generating (SOG) agents is a major research focus for its utility in photodynamic therapy, wastewater treatment, material science, and organic synthesis. Photosensitization of ambient oxygen using organic dyes is an efficient approach to generating SO, though their efficiency is often severely hampered due to aggregation-induced deactivation. In this manuscript, we present the utility of bile salt micelle as supramolecular host for promoting SOG in aqueous media for a BODIPY dye, which was otherwise highly inactive. The SOG efficiency in test media was probed by monitoring the oxidation of 1,5-Dihydroxy Naphthalene (DHN) to corresponding quinone (juglone) through spectroscopic and chromatographic methods. In this study, we investigated the use of bile salt micelles as a supramolecular platform for enhancing the SOG efficiency of a BODIPY dye in aqueous media through complexation. Our results show that sodium cholate micelles can solubilize the hydrophobic dye and enhance its ability to generate singlet oxygen, while traditionally used macrocyclic hosts such as Β- and γ-cyclodextrin complexation was found to be far less efficient. Computational modeling revealed that the bile salt micelles form an aggregated complex structure with the dye, leading to improved supramolecular interactions and photophysical properties. This work demonstrates the potential of bile salt micelles as a natural and safe platform for enhancing the activity of nonpolar dyes for PDT applications.

Keywords: Singlet oxygen; Bile salt micelle; Sodium cholate; Cyclodextrins; Supramolecular chemistry; Photodynamic therapy; Photochemistry.

Introduction

Singlet Oxygen (SO) refers to the electronically excited spin isomer of ambient triplet oxygen [1,2]. As a highly reactive excited state intermediate generated in atmospheric and biological systems, it possesses significance in many processes such planetary chemistry, photosynthesis [3,4], oxidative stress [5], immune response [6], and cellular signaling [7]. Singlet Oxygen Generation (SOG), its reactivity [8-10], and excited state dynamics are the subject of much research interest in medical technologies leading to the development of therapeutic modality known as photodynamic therapy [11,12], which is implemented in treatment of certain types of cancer, skin conditions [13-15], macular degeneration [16], acne [17], and psoriasis [18]. The importance of this species is demonstrated by the sheer volume of published works that document its reactivity, excited state dynamics, and behavior in different media and versatility in its applications. Thus, there is significant interest in designing new dyes and methodologies to generate SO for afore-mentioned applications.

There is vast literature of designed photosensitizers with competitive SOG efficiencies, relatively little effort is dedicated towards non-covalently finetuning the dyes to improve activity. In this context there have been supramolecular photochemistry efforts that have utilized weak interactions, such as through host-guest chemistry, to increase SOG [19-21]. Herein we report the use of bile salt micelles in enabling a BODIPY dye to efficiently generate singlet oxygen in aqueous medium through complexation. Our efforts, as outlined in this manuscript, leads to understanding of the supramolecular interactions that lead to enhancement of activity, and serves as a demonstration of a natural and benign surfactant as promising and safe platform for solubilizing a simple and otherwise inactive dye for generating SO without covalent modification.

Though there are notable works and a broad literature of supramolecular SOG in micelles, there has been no such report for the same in bile salt micelle. Thus, this work is expected to intrigue researchers in relevant fields to explore bile salt micelles as potential drug delivery agents in the context of PDT and otherwise.

Bile Salt Micelles

In this study we employed two supramolecular hosts systems – sodium cholate micelles (a bile salt) [22] and cyclodextrins – to manipulate the SOG efficiency of a BODIPY dye, which was remarkably hampered in water, compared to methanol, due to aggregation-induced non-radiative relaxation. Cyclodextrins, cucurbiturils, dendrimers, and other macromolecular hosts, and traditional surfactants are well-known macromolecular systems that have been used to disaggregate dyes to achieve photophysical manipulation [19]. However, bile-salt micelles (Figure 1) have not been used in this context despite their practically useable low toxicity as drug delivery agent, unique host-guest characteristics, and demonstrated ability to solubilize drug molecules [23-25]. They are a relatively less known supramolecular system and have not been used in a similar context to the best of our knowledge. They are physiologically produced in mammals and play an important role in fat digestion [26,27]. These steroidal compounds, unlike synthetic surfactants, display highly unusual aggregation behavior. For one they have traversal spatial distribution of polar and non-polar groups leading to a small aggregation number (3 to 7), standing/upright aggregate structure, and low CMC [28]. They also undergo stepwise micelle formation wherein at very low concentrations three to five monomers self-assemble to form primary aggregates, and as concentration increases, the primary aggregates further assemble in weakly held networks to form secondary aggregates. Thus, the primary and secondary aggregates afford two different binding sites for guests as shown in Figure 2.