A Spin-orbit Coupling Study on the Quinoline-and Porphyrin-based Photosensitizers

The spin-orbit coupling（SOC） of four porphyrin- and quinoline-based compounds has been studied using Pauli-Breit SOC operator with one- and two-electron terms. The results revealed that the yield of singlet oxygen is affected by the spin-orbit coupling matrix element involving the emitting triplet and the perturbing singlet state. Investigated quinoline-based compounds have more high SOC values than those porphyrin-based compounds due to spin parallel electron pairs of oxygen. The open shell d8 of metal Pt can induce the stronger exchange interactions than the closed shell p6 of metal Mg, resulting in bigger SOC matrix element in quinoline-based Pt complex than in the quinoline-based Mg complex. Simultaneously, potential energy curves of the first excited sate and the first triplet sate have been calculated, which proves that all investigated complexes can induce singlet oxygen. These computational findings support quinolin-based compounds have high singlet oxygen yields and provide a rigorous basis for predicting the probability of singlet oxygen yields in plane-type molecules.

<i>In Vitro</i>Effects of Photodynamic Therapy with Three Photosensitizers on <i>Candida</i>spp from Complicated Vulvovaginitis and Asymptomatic Women

Aim: To evaluate photodynamic therapy (PDT) in vitro to reduce the growth of Candida spp, and its synergy with the antifungals fluconazole and ketoconazole for inhibition of resistant, DDS and susceptible isolates from asymptomatic carriers and with complicated vulvovaginitis. Methods: Between 2017 and 2020, we evaluated 230 women with vulvovaginal candidiasis and 400 asymptomatic. We obtained 130 positive cultures for Candida spp from vulvovaginitis and 94 asymptomatic. Yeasts were characterized by classical and molecular tests. Sensitivity to fluconazole and ketoconazole was evaluated by E-test. We used photodynamic light through blue LED, wavelengths between 450 to 470 nm, power of 260 mW, energy fluence of 270 J/cm2, for 15 minutes over all colonies of Candida spp. Methylene blue (MB) at 450 mg/mL, 2% gentian violet (VG) and 50 μM curcumin (CR) were used in association or not with LED irradiation. Suspensions of Candida spp of 106 CFU/mL, subjected to the different assays, were introduced in 96-well microplates, incubated for 48 hours at 35˚C and the readings at 530 nm. The samples were finally cultivated in Petri plates containing Sabouraud dextrose agar to assess the growth inhibition. All procedures were in triplicate. Results: C. albicans was prevalent in vulvovaginal candidiasis, however, we also isolated non-albicans species such as C. glabrata, C. tropicalis and C. parapsilosis. There was a substantial reduction (66.6% to 83.8%) of the CFU/mL of the isolates treated with FDT. Gentian violet at 2% alone reduced the growth of CFU/ml of Candida spp from 69% to 75%. Among isolates of vaginitis and asymptomatic carriers, after using FDT, we found a reduction in resistant phenotypes and DDS for fluconazole in percentages from 20% to 100% for C. albicans, from 50% to 100% C. glabrata, 33.3% to 100% C. parapsilosis and 100% C. tropicalis. For ketoconazole in the same isolates, there was a reduction in phenotypes with MIC > 16 μg/mL of up to 50% in C. albicans, 50% to 100% C. glabrata, 50% to 100% C. tropicalis. Conclusions: PDT with MB, GV and CR revealed efficacy in vitro in reducing the growth of C. albicans and non-albicans, especially due to chronic recurrent vulvovaginitis.

Green Synthesis of New Tetra Schiff Bases and Bis-Azo Bis-Schiff Bases Derived from 2,6-Diaminopyridine as Promising Photosensitizers

Nine new tetra Schiff bases (M2 - M9) were prepared in moderate yields via the condensation of different aromatic amines and bis-Schiff base (M1) in microwave synthesizer. Also five new azo-Schiff bases (M16 - M20) were prepared by the condensation of (M1) with the azo-salicylaldehyde (M11 - M15) using the same method. The green synthesis by microwave irradiation was chosen as route due to its novelty, cleanliness, efficiency, time and solvent saving properties compared with the conventional methods which lack these advantages;such as time consume and wasting environment polluting organic solvents to achieve the same efficiency in synthesis. The prepared compounds which are believed by us to be competent as photosensitizers in photochemical systems were identified by IR and NMR spectroscopy besides elemental analysis.

Plant extracts as natural photosensitizers in photodynamic therapy:in vitro activity against human mammary adenocarcinoma MCF-7 cells

Objective: To examine three plant extracts [Lumnitzera racemosa(Combretaceae)(L.racemosa), Albizia procera(Fabaceae)(A.procera) and Cananga odorata(Annonaceae)] for their potential as source of photosensitizers in photodynamic therapy.Methods: Human mammary adenocarcinoma(MCF-7) cells were treated with the plant extracts, which were irradiated with 5.53 m W and 0.553 mW broadband light.Cell viability was assessed using MTT assay and induction of apoptosis was determined using terminal deoxynucleotidyl transferase-dUTP nick end labeling assay.Results: The crude ethanolic extracts, independently, were nontoxic against cancer and non-cancer cells but when irradiated with 5.53 mW broadband light, L.racemosa and A.procera extracts were cytotoxic against MCF-7 with IC_(50) of 11.63 mg/mL and10.73 mg/mL, respectively.With 0.553 mW broadband light, the IC_(50) values were higher at 17.14 mg/mL and 19.59 mg/mL, respectively.Photoactivated L.racemosa and A.procera extracts were found to be more cytotoxic against MCF-7 than the non-cancer cell line, human dermal fibroblast-neonatal.Moreover, the cytotoxicity of the extracts was mediated by apoptosis.Conclusions: Two of the plant extracts used, L.racemosa and A.procera were toxic and induced apoptosis to mammary cell adenocarcinoma, MCF-7 when photoactivated.These extracts were also more toxic to human cancer than non-cancer cell lines.

PEGylated liposomal photosensitizers as theranostic agents for dual-modal photoacoustic andffuorescence imaging-guided photodynamic therapy

The photosensitizer(PS)as photodynamic therapy(PDT)agent,can also serve as the contrast agent for dual-modalffuorescence imaging(FLI)and photoacoustic imaging(PAI)for precise cancer theranostics.In this study,the PAI capability of commercial PS,benzoporphyrin derivative monoacid ring-A(BPD)were examined and compared with that from the other PSs and dyes such as TPPS_(4),Cy5 dye and ICG.We discovered that BPD exhibited its advantage as contrast agent for PAI.Meanwhile,BPD can also serve as the contrast agent for enhanced FLI.In particular,the PEGylated nanoliposome(PNL)encapsulated BPD(LBPD)was produced for contrast enhanced dual-modal FLI and PAI and imaging-guided high-efficiency PDT.Enhanced FLI and PAI results demonstrated the significant accumulation of LBPD both within and among individual tumor during 24 h monitoring for in vivo experiment tests.In-vitro and in-vivo PDT tests were also performed,which showed that LBPD have higher PDT efficiency and can easily break the blood vessel of tumor tissues as compared to that from BPD.It was discovered that LBPD has great potentials as a diagnosis and treatment agent for dual-modal FLI and PAI-guided PDT of cancer.

Assembled Photosensitizers Applied for Enhanced Photodynamic Therapy

Photodynamic therapy(PDT)has emerged as an efficient method for cancer therapy.However,traditional photosensitizers(PSs)always have low bioavailability.For example,hydrophobic PSs tend to aggregate in cells and lead to aggregation-induced quenching;while hydrophilic PSs that have good solubility in water systems can hardly penetrate into cells whose membranes are lipophilic.To overcome these drawbacks,suitable PSs that meet the requirements of PDT are needed.Numerous investigations have been introduced,especially the molecular-assembly technique that can increase the bioavailability of PSs during the tumor therapy process.Besides,increasing the quantum yield of reactive oxygen species(ROS)by adjusting the PS triplet state lifetime as well as developing aggregation-induced emission(AIE)agents can also improve the PDT effect.This review summarizes the molecular-assembly technique to obtain intelligent PSs to achieve high PDT efficiency.First,increasing the quantum yield of ROS by decreasing the energy gap between S_(1)and T_(1)states or increasing the spin–orbit coupling Hamiltonian are introduced.Second,we present the bioavailability of traditional PSs by improving the amphiphilicity of the PSs or using intelligent nanostructures.Then,the AIE PSs that can form ROS in the aggregated state under irradiation are described.Finally,the perspective and challenges of PDT are discussed.

Treatment of Alzheimer's disease with small-molecule photosensitizers

Alzheimer's disease is a neurodegenerative disease that signals for excessβ-amyloid(Aβ)aggregation.Although people have made great attempts to control the aggregation of Aβ,no effective medications have been produced yet.Due to its excellent temporal and spatial selectivity,photodynamic treatment has been gradually employed and interfered in the aggregation process of Aβ,with some achievement.To enhance the research and application of photodynamic therapy in Alzheimer's disease,this paper reviews the progress of small-molecule photosensitizers in the treatment of Alzheimer's disease in recent years and outlines existing tactics and potential obstacles.

Cationic telluroviologen derivatives as type-I photosensitizers for tumor photodynamic theranostics

The hypoxia of the tumor microenvironment(TME)seriously restricts the photodynamic therapy(PDT)effect of conventional type-II photosensitizers,which are highly dependent on O_(2).In this work,a new type-I photosensitizer(TPE-TeVPPh3)consisting of a tetraphenylethylene group(TPE)as a bioimaging moiety,triphenyl-phosphine(PPh3)as a mitochondria-targeting group,and telluroviologen(TeV2+)as a reactive oxygen species(O_(2)•−,•OH)generating moiety is developed.The luminescence intensity of TPE-TeV-PPh3 increased significantly after specific oxidation by excess H2O2 in the TME without responding to normal tissues via the formation of Te═O bond,which can be used for monitoring abnormal H2O2,positioning,and imaging of tumors.TPE-TeV-PPh3 with highly reactive radicals generation and stronger hypoxia tolerance realizes efficient cancer cell killing under hypoxic conditions,achieving 88%tumor growth inhibition.Therefore,TPE-TeV-PPh3 with low phototoxicity in normal tissue achieves tumor imaging and effective PDT toward solid tumors in response to high concentrations of H_(2)O_(2)in the TME,which provides a new strategy for the development of type-I photosensitizers.

An updated overview on the development of new photosensitizers for anticancer photodynamic therapy

Photodynamic therapy(PDT), based on the photoactivation of photosensitizers(PSs), has become a well-studied therapy for cancer. Photofrin~?, belonging to the first generation of PS, is still widely used for the treatment of different kinds of cancers; however, it has several drawbacks that significantly limit its general clinical use. Consequently, there has been extensive research on the design of PS molecules with optimized pharmaceutical properties, with aiming of overcoming the disadvantages of traditional PS, such as poor chemical purity, long half-life, excessive accumulation into the skin, and low attenuation coefficients. The rational design of novel PS with desirable properties has attracted considerable research in the pharmaceutical field. This review presents an overview on the classical photosensitizers and the most significant recent advances in the development of PS with regard to their potential application in oncology.

Mitochondria-localized iridium(Ⅲ) complexes with anthraquinone groups as effective photosensitizers for photodynamic therapy under hypoxia

Photodynamic therapy(PDT)is a potential way for the tumor treatment.However,it notably suffers the limitation of hypoxia in solid tumors.Thus,it is significant to develop effective photosensitizers which can exhibit excellent therapeutic performance under both normoxia and hypoxia.Herein,we reported four ionic iridium(Ⅲ)complexes(Irl-Ir4)with anthraquinone groups which can regulate their excited state energy levels effectively.Among them,the energy gap of Ir1 was between 1.63 and 2.21 eV,which can match well with that of O2,and the HOMO energy of Ir1 is less than-5.51 eV.Compared with Ir2-Ir4,the luminescent quantum efficiency of Irl was the highest.Particularly,Ir1 can specifically target the mitochondria of the tumor cells.Meanwhile,Ir1 showed high singlet oxygen quantum yields(Ф△)in both solutions and living cells with low cytotoxicity.The results of PDT experiments revealed that Irl,as a photosensitizer,exhibited excellent therapeutic effect not only in normoxia but also in hypoxia condition.We believe that this work is meaningful for developing excellent PDT agents based on cyclometalated Ir(III)complexes via rational ligand modification.

THERAPEUTIC EFFECTS OF PHOTOSENSITIZERS IN COMBINATION WITH LASER AND ACNU ON AN IN VIVO OR IN VITROMODEL OF CEREBRAL GLIOMA

This study investigated the independent and combined effects of photodynamic therapy (PDT), laser photodynamic hyperthermia (LPDH) and 1-(4-amino-2-methyl-5-pyrimidinyl) methy1-3-(2-chloroethyl) -3-nitrosourea hydrochloride (ACNU) in a rat 9L induced gliosarcoma model. The mortality rate (MR60), mean survival time (MST60), and increasing life span (ILS60) within 60 days were determined to evaluate the therapeutic effect in vivo. The MR60 and MST60 of the gliosarcoma tumor control were 100% and 16.2 days. The ILS60s of PDT and ACNU were 72.84% and 49.81%, respectively, but MR60 of both were 86.72%. All combined treatments produced significantly prolonged survival (P<0.01). The combined effects of LPDH and ACNU, MR60, MST60, and ILS60 were 60%, 43 days, and 165.4%, respectively. The ILS60 of PDT+ACNU (96.48%) and PDT+LPDH (98.58%) also indicated a synergistic or additive effect. The survival fraction and synthetic rate of DNA, RNA, and protein of glioma 9L tumor cells in vitro after single treatment of PDT or combined with antitumor drugs and laser showed that the cytotoxicity of PDT to 9L tumor cell was obvious by using Rh123, HPD, and Pf-Ⅱ as photosensitizers. Combined treatments of PDT, antitumor drugs, and laser suppressed the synthesis of DNA, RNA, and protein more significantly than single treatment with PDT.

Synthesis and Characterization of Novel Schiff Base for Enhanced Dye-Sensitized Solar Cell Photo-Response Mechanism

The efficient photo-response mechanism is one of the key factors in the commercialization of dye-sensitized solar cells in a bid to satisfy renewable energy demands. Progress in green technology has put solar energy on the front burner as a provider of clean and affordable energy for a sustainable society. We report the synthesis of a novel Schiff base with optical transparency in the visible and near IR region of the solar spectrum that can find application in the DSSCs photo-response mechanism. The synthesized crystal exhibited features that could handle some of the shortcomings of dye-sensitized solar cells which include wide band solar spectrum absorption and capability for swift charge transfer within the photoelectrodes. The synthesized Schiff base was characterized using x-ray diffractometer, UV/Visible spectrometer, Frontier transmission infrared spectrometer and conductometer. XRD data revealed the grown crystal to have an average crystallite size of 2.08 nm with average microstrain value of about 269.43. The FT-IR recorded transmission wave ѵ (CO) at 1207.7 cm−1 while dominant wave occurred at ѵ1654.9 and ѵ1592.3 cm−1 relating to ѵ (CN) stretching and ѵ (NH) bending respectively were observed. The IR spectrum revealed the bonding species and a probable molecular structure of 2,6-bis(benzyloxy)pyridine. The UV/Visible spectra convoluted to maximum peak within the near IR region suggesting that 2,6-bis(benzyloxy)pyridine can absorb both the visible and near IR region while its electrical conductivity was determined to be 4.58 µS/cm. The obtained result of the present study revealed promising characteristics of a photosensitizer that can find application in the photo-response mechanism of DSSCs.

Photosensitizers with Aggregation-induced Emission and Their Biomedical Applications

Microorganisms and cancer have always been the fierce enemies of human beings,but the traditional methods of treating them still have many defects.Therefore,it is extremely important to develop rapid,effective and safe treatments.Photodynamic Therapy(PDT)has attracted much attention because of its advantages of non-invasive,non-drug tolerance,high selectivity and low toxicity.As a result,more and more scientists are committed to developing better photosensitizers to enhance the efficiency of PDT in the therapy of microorganisms as well as tumors.The discovery of aggregation-induced emission(AIE)phenomenon provides a novel research direction for the progress of photosensitizer and brings a broader prospect for PDT.This review focuses on the recent progress of photosensitizers(PSs)with AIE properties in PDT from two aspects of anti-microbial and anti-cancer.Among them,anti-microbial aspects were introduced from the perspectives of anti-bacterial,anti-fungal and anti-viral aspects,while anti-cancer aspects were first introduced from the perspective of different target sites of photosensitizers,and then based on the modification of their own structures.Finally,the current limitations,challenges and future development of AIE photosensitizer(AIE-PSs)are clarified in view of the existing strategies and obstacles,so as to promote the development of AIE-PSs in the future clinical applications.

Protection of Photoactivity of Photosensitizers by Amphiphilic Polysaccharide Micelles

Photosensitizer （photosan）-encapsulated micelles were prepared by self-assembly of Photosan with two amphiphilic polysaccharide derivatives, including the cholesteryl conjugated sodium alginate derivative （CSAD） and the deoxycholic acid group conjugated chitosan derivative （DA-Chit）. The results of UV-Vis and fluorescence spectroscopy indicated that the hydrogen bonding strength dominated the micelle formation. Methyl viologen was used as a model quencher of photosan. Using the steady-state fluorescence technology, the quenching constants were determined to be 2.05, 1.88 and 0.30 L/mmol for the free photosan, the photosan-CSAD micelle and the photosan-DA-Chit micelle, respectively. This suggested that photosan was protected from quenching of methyl viologen by the polysaccharide micelles. In addition, the protection effect of the photosan-DA-Chit micelle was significantly stronger than that of the photosan-CSAD micelle. The photosan-DA-Chit micelle is thus anticipated for protection of photoactivity of photosan during the blood circulation process in vivo.

Radical induced quartet photosensitizers with high ^(1)O_(2) production for in vivo cancer photodynamic therapy

Singlet oxygen(^(1)O_(2)) is a strong oxidant which plays important roles in photodynamic therapy(PDT). The exploitation of photosensitizers with high ^(1)O_(2) production is crucial to improve PDT efficiency. In this study, a radical labeled quartet photosensitizer Cy-DENT is reported with high singlet oxygen quantum yield(Φ_(Δ)=32.3%) due to a radical enhanced inter-system crossing(ISC) process. After the introduction of 2,2,6,6-tetramethylpiperidinyloxy(TEMPO) radical, quartet state ^(4)[R,T] of CyDENT could be formed to give an over 20-fold enhancement of singlet oxygen quantum yield compared to Cy-DEN(without TEMPO radical) under irradiation of near infrared(NIR) light. In addition, the ^(1)O_(2 )production is well controlled by varying the electron-donating ability of the terminal substituent group. Cy-DENT possesses good cell permeability and is localized in mitochondria. Under the irradiation of 700 nm light, Cy-DENT can produce high levels of ROS to destroy the mitochondria membrane potential and induce cell apoptosis. Through the encapsulation of PEG-SS-PCL micelle, Cy-DENT can be effectively delivered to tumors and suppresses the tumor growth after PDT treatment.

Molecular mechanics study on conformation of perylene-quinonoid photosensitizers

Using molecular mechanics method,values of the heat of formation (HF) of different conformations,of perylenequinonoid photosensitizes hypocrellin A (HA) and hypocrellin B (HB) were calculated and the variance of HF after phenolic protons’ dissociation were calculated as well The following was found:(i) The HF values of lour conformational isomers of HA and HB are similar to each other,so the four isomcrs can transform to each other room temperature,(ii) There exists the difference between the ability of dissociation of phenolic protons of HA and that of HB,the former is higher than the latter (iii) There exist two intramolecular hydrogen bonds in HA and HB The bond energy is approximately 8 kJ/mol and the energy of conformation Ⅰ is lower than that of conformationⅡ The bond energy of HA is lower than that of HB.(iv) There exists a low energy snot when phenolic hydroxyl bond twists 180° from the position where hydrogen bond is formed,which suggests that this kind of conformation probably exists,(v)

Aggregation Turns BODIPY Fluorophores into Photosensitizers:Reversibly Switching Intersystem Crossing On and Off for Smart Photodynamic Therapy

We report for the first time a practical and simple supramolecular approach to turn fluorophores into photosensitizers(PSs).Using boron dipyrromethene(BODIPY)as a proof-of-concept,eight BODIPY derivatives manifest bright fluorescence and generate negligible singlet oxygen in solution.In contrast,aggregation fails to emit fluorescence and enhances singlet oxygen generation.Experimentally,these aggregates have excellent photodynamic therapy(PDT)performance,and one even exhibits much stronger photocytotoxicity than the commercialized PS Ce6 under identical conditions.Theoretical studies show that this property originated from significantly reduced energy gaps between relevant excited singlet and triplet states,leading to considerably improved intersystem-crossing efficiency.Importantly,a simple disaggregation recovers the original properties of the fluorophores.This reversible switching property between fluorophores and PSs assists the development of smart PDT systems,in which singlet oxygen generation in tumors can be controlled in an intelligent manner after PDT treatment.The present work provides a novel strategy to design heavy-atom-free PSs and may pave the way to the development of smart PDT systems.

Fine-mapping and transcriptome analysis of the photosensitive leaf-yellowing gene CaLY1 in pepper(Capsicum annuum L.)

Leaf color is directly related to altered photosynthesis.Hence,leaf yellowing mutants can be widely used for the researching plant physiology and functional genomes,for cultivating new varieties of popular horticultural plants,and for identifying hybrid purity(as markers).Here,we constructed a^(60)Co-γF_(2)population from the leaf-yellowing mutant R24 via radiation mutation with the inbred line WT21 of pepper.Genetic analysis showed that the leaf-yellowing of the mutant was controlled by a single recessive gene.By applying the Bulk Segregation Analysis and Kompetitive Allele Specific PCR markers,the leaf-yellowing gene CaLY1(Capsicum annuum Leaf yellow 1)was mapped on chromosome 9,SNP5791587-SNP6011215,with a size of 214.5 kb.One non-synonymous mutated gene Capana09g000166 was found in the interval.The gene encoded a Psb X,which is the core complex of PSⅡ.Transcriptome analysis further showed that 2301 differentially expressed genes were identified under shading treatment for 24 h in R24.The Gene Ontology enrichment pathways were related to photosynthesis light harvesting,cell wall,activity of quercetin 3-O-glucosyltransferase and flavonoid metabolic process,which likely regulate the response of pepper leaves to different light levels.Functional enrichment analysis indicated that the most abundant pathways were photosynthesis antenna proteins and metabolic.

Passivation engineering via silica‐encapsulated quantum dots for highly sensitive photodetection

Organometal halide perovskites are promising semiconducting materials for photodetectors because of their favorable optoelectrical properties.Although nanoscale perovskite materials such as quantum dots(QDs)show novel behavior,they have intrinsic stability issues.In this study,an effectively silane barrier-capped quantum dot(QD@APDEMS)is thinly applied onto a bulk perovskite photosensitive layer for use in photodetectors.QD@APDEMS is synthesized with a silane ligand with hydrophobic CH_(3)-terminal groups,resulting in excellent dispersibility and durability to enable effective coating.The introduction of the QD@APDEMS layer results in the formation of a lowdefect perovskite film with enlarged grains.This is attributed to the grain boundary interconnection effect via interaction between the functional groups of QD@APDEMS and uncoordinated Pb^(2+)in grain boundaries.By passivating the grain boundaries,where various trap sites are distributed,hole chargecarrier injection and shunt leakage can be suppressed.Also,from the energy point of view,the deep highest occupied molecular orbital(HOMO)level of QD@APDEMS can work as a hole charge injection barrier.Improved charge dynamics(generation,transfer,and recombination properties)and reduced trap density of QD@APDEMS are demonstrated.When this perovskite film is used in a photodetector,the device performance(especially the detectivity)stands out among existing perovskites evaluated for energy sensing device applications.