Optical Properties of Disulfiram and Its Metal Complexes Toward the Photoactive Anticancer Effects
Authors: Saitsu Ayumi , Sakai Riku , Tsuruoka Hanna , Terashima Yuya , Nakayama Yasuo , Yamada Taisei , Guan Sujun , Hunge Yuvaraj Mohan , Terashima Chiaki 
Published: December 2024

Introduction

Disulfiram (DSF) has been used for nearly 70 years as an antidrug and is clinically safe. Recently, it has attracted widespread attention, because it was shown through screening to be effective as an anticancer agent. 1) However, further improvement of the efficacy of DSF is required before it can be used as a therapeutic agent. In this study, we focused on metal diethyldithiocarbamate complexes formed by DSF and metal ion (Cu2+, Fe3+), respectively, to improve the efficacy of the drug by applying it to photodynamic therapy. It aimed to enhance the photoresponses of DSF, with Cu complex (DSF-Cu) and Fe complex (DSF-Fe), and to further improve the anticancer effects with the enhanced photoresponses.

Methods

Cyclic voltammetry (CV) measurements were performed to determine the electrochemical response of each sample and to investigate their redox properties. In addition, electrochemical impedance spectroscopy (EIS) measurements were conducted under both UV light and dark conditions using a carbon plate coated with the samples as the working electrode to investigate the photo-responsiveness of the samples. Methylene blue (MB) degradation tests were then carried out based on JIS R 1703-2: 2014 to assess whether light irradiation of each sample improves the degradation of organic matter. The HOMO-LUMO levels were estimated by photoelectron yield spectroscopy (PYS) measurements and diffuse reflectance spectroscopy.

Results and Discussion

From CV results, it could be clearly found the oxidation and reduction peaks for DSF, DSF-Cu, and DSF-Fe, indicating that all samples exhibit an electrochemical response. The EIS results also showed that the radius of the capacitive semicircle was reduced by UV irradiation for all samples, which is considered to be due to the decrease in charge transfer resistance as the charge carriers are transferred more efficiently by UV irradiation. The MB degradation test showed a relatively clear MB degradation rate for DSF-Fe (Figure 1). The reason for the difference in MB degradation rates among the samples can be considered to be the difference in reactive oxygen species (ROS) production ability based on the relationship between the HOMO-LUMO gap position and the oxidation/reduction potentials of water and oxygen in each sample. From the estimated HOMO-LUMO level of each sample, it could find that the reduction potential of oxygen (O2/O2
―: -0.46 V at pH 7) was below the LUMO level in all samples, but the oxidation potential of water (O2/H2O: 0.81 V at pH 7) and the oxidation potential of MB potential (>1.2 V) did not exceed the HOMO level (Figure 2). Therefore, it is possible that MB was oxidatively decomposed by O2
― produced by the sample's own oxidation and reduction of dissolved oxygen. The difference in the decomposition rate may be due to the difference in the recombination speed of excited electrons. The respective gap energies suggest that DSF-Cu and DSF-Fe can also respond to visible light.

[References]

(1) Yuya Terashima, et al., Nature Communications 11 (609), 2020.

(2) S. Trasatti, Pure & Appl Chem. 58 (7), 955-966, 1986.

Figure 1