Synthesis and Photochemical Characterization of Novel 10-Cyclo Biladiene Derivatives

Date
2024-05
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University of Delaware
Abstract
Photodynamic therapy (PDT) is an alternative cancer treatment which utilizes a photosensitizer to generate a cytotoxic singlet oxygen species upon light irradiation. The efficacy of PDT relies heavily upon the photochemical properties of the photosensitizer, properties which many commercially approved photosensitizers lack. Subsequently, much work has been done focusing on the development of a photosensitizer which is capable of strongly absorbing light within the phototherapeutic window, and which displays a high singlet oxygen quantum yield. Previous work in the Rosenthal group resulted in the development of Pd[DMBil1], a compound which has shown great potential as a photosensitizer for PDT. This compound, however, is unable to strongly absorb light within the phototherapeutic window, and thus has been the target of modification and functionalization to refine the spectroscopic and photophysical characteristics of the framework to refine its properties so that it may be a more potent photosensitizer. Investigation into the extension of the absorbance profile of the scaffold has resulted in the substitution of the sp3 hybridized geminal substituents at the 10- position of the compound with cyclic carbon chains, resulting in a novel family of cyclobiladiene derivatives, namely Pd[CHBil1], Pd[CPBil1], and Pd[CBBil1]. The introduction of these groups aims to investigate the impact of incorporating a bulky, non-electronically active substituent, and to increase the strain on the complex, and examine the spectroscopic and photophysical characteristics of the resulting compounds. It was found that the introduction of these groups has drastic impacts on many of the photochemical properties of the Pd[DMBil1] scaffold, which were characterized through UV-Vis absorption spectroscopy in order to assess steady-state spectroscopic characteristics. It was revealed that substitution of the 10-position with cyclic carbon chains led to an overall decrease in molar absorptivity, coupled with a slight redshift in absorbance compared to their parent compound, Pd[DMBil1]. In addition, Pd[CHBil1] exhibited a significantly lower molar absorptivity than Pd[CBBil1], with a difference of 17,000 M-1 cm-1 at their respective λmax. Furthermore, when compared to Pd[DMBil1] derivatives with a phenyl-substituted 10-position (Pd[MPBil1] and Pd[DPBil1]), the cyclobiladienes displayed an increased λmax but a lower molar absorptivity across all wavelengths. The findings of this study offer valuable insights into the relationship between structure and photochemical properties of the Pd[DMBil1] scaffold and its potential as a photosensitizer for PDT. The observed changes in spectroscopic properties upon substitution at the 10-position contribute to a more well-rounded understanding of the mechanisms of these compounds. Moreover, the results of this work offer guidance for the rational design and development of future biladiene-based photosensitizers with optimized properties for PDT Further studies on the singlet oxygen quantum yield of these novel Pd[DMBil1] derivatives are warranted to fully assess their potential as PDT agents.
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