Photochemical Study of Vitamin K and Vitamin B Derivatives and Their Applications as Photo-induced Antimicrobial Agents

The photoactivity of a series of vitamin K and vitamin B derivatives was investigated systematically by combining theoretical and computational modeling methods with empirical evidences and experiments. The photochemical properties of lipophilic vitamin K derivatives, including vitamin K1, K2, K3, and K4, water-soluble vitamin K3, as well as water-soluble vitamin B2 derivatives including riboflavin and flavin mononucleotide, are the examples discussed in this work. Some of the vitamins are proven to efficiently generate oxidative triplet excited state (T1) and reactive oxygen species (ROS), such as hydroxyl radicals (HO·), hydrogen peroxide (H2O2), and singlet oxygen (1O2), via the intersystem crossing (ISC) process followed by the type I or type II photoreaction under proper photoirradiation conditions. The generated active species are non-selectively and efficiently bio-lethal to diverse microorganisms including Gram-positive and Gram-positive bacteria, as well as viruses. Meanwhile, some vitamins exhibit excellent photoinduced antimicrobial durability while maintaining their robust antimicrobial function under long-term photo exposure, representing the good photosensitizer nature of these vitamins. In this dissertation, chapter 1 introduces the basic photochemistry principles and photoreaction mechanisms of the aromatic ketone, the parent structure of vitamin K derivatives. Representative inorganic and organic photosensitizers are then identified and discussed. Meanwhile, some natural photosensitizers that can be extracted from natural products are screened. The photoactivity and photochemical properties of some common vitamins are presented as well. In Chapter 2, the photochemistry of the lipophilic vitamin K1-4 is discussed in detail by employing the Gaussian computational modeling package. Vitamin K3 was proven the robust photosensitizer in generating either HO· or 1O2 via type I or type II photoreaction among four vitamin K derivatives. In the following experiments, vitamin K3 demonstrated its highly efficient photoinduced antibacterial function and excellent durability against both Gram-negative and Gram-positive bacteria under daylight irradiation. The successful combination of the theoretical modeling and experiments provides a solid platform to study the photochemistry of photosensitizers at the molecular level. In Chapter 3, vitamin K1, vitamin K3, or vitamin K4 were blended with hydrophobic polyacrylonitrile (PAN) or hydrophobic poly (vinyl alcohol-co-ethylene) (PVA-co-PE) and electrospun to nanofibrous membranes with fibrous diameters of 200-290 nm. The VK3/PVA-co-PE nanofibrous membrane was proven to be the most efficient photoactive nano-membrane in generating ROS under daylight irradiation. The VK3/PVA-co-PE nanofibrous membrane exhibits robust and non-selective microbicidal performance against Gram-negative Escherichia coli bacteria, Gram-positive Listeria innocua bacteria, T7 bacteriophage virus, and Feline Infectious Peritonitis coronavirus under daylight irradiation. Excellent photoinduced antimicrobial durability of the VK3/PVA-co-PE nanofibrous membrane was proven, which confirms the conclusion in chapter 2 and indicates that the application potential of VK3 as a daylight-induced antimicrobial agent was promising. In chapter 4, the photoactivity of a water-soluble vitamin K3, menadione sodium bisulfite (MSB), is discovered and discussed in detail for the first time. It was proven that the triplet MSB could efficiently inactivate bacteria even in the absence of hydrogen donors under UVA (365 nm) irradiation. The determinant factor that affects the photoinduced antibacterial function of MSB is the distance between the photoactive site and the target microorganisms. Excellent photoinduced antibacterial durability of MSB was observed, indicating the photochemical reaction cycles of vitamin Ks with the aromatic ketone structure. In chapter 5, the photochemistry of two water-soluble vitamin B2 derivatives, riboflavin (RF) and flavin mononucleotide (FMN) was studied and discussed. Both RF and FMN were found to produce H2O2 and 1O2 via type I or II photoreaction due to the formation of the oxidative T1. However, RF and FMN show limited photoinduced antibacterial function against bacteria under cool white (370-750 nm) or UVA irradiation. The RF/PVA-co-PE and FMN/PVA-co-PE nanofibrous membranes exhibit good photoinduced antibacterial function against bacteria under UVA irradiation, which is probably due to the intimate contact of the photoactive nanofibrous membranes with target bacteria. Therefore, a close bacterial contact should be provided to RF or FMN to achieve better photoinduced antibacterial performance. The final chapter concludes the photochemistry and photoactivity of vitamin derivatives and their photoinduced antimicrobial function, which may be applied in the fabrication of safe-to-use, highly efficient, extremely durable, and environmentally friendly photoinduced antimicrobial materials that can be applied in bioprotection and food safety related areas