Photoactive Compound Research Articles

Extracorporeal photopheresis and its role in heart transplant rejection: prophylaxis and treatment.

Heart transplantation is the gold standard therapeutic option for select patients with end-stage heart failure. Unfortunately, successful long-term outcomes of heart transplantation can be hindered by immune-mediated rejection of the cardiac allograft, specifically acute cellular rejection, antibody-mediated rejection, and cardiac allograft vasculopathy. Extracorporeal photopheresis is a cellular immunotherapy that involves the collection and treatment of white blood cells contained in the buffy coat with a photoactive psoralen compound, 8-methoxy psoralen, and subsequent irradiation with ultraviolet A light. This process is thought to cause DNA and RNA crosslinking, ultimately leading to cell destruction. The true mechanism of therapeutic action remains unknown. In the last three decades, extracorporeal photopheresis has shown promising results and is indicated for a variety of conditions. The American Society for Apheresis currently recommends the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma, scleroderma, psoriasis, pemphigus vulgaris, atopic dermatitis, graft-versus-host disease, Crohn's disease, nephrogenic systemic fibrosis, and solid organ rejection in heart, lung, and liver transplantation. In this review, we aim to explore the proposed effects of extracorporeal photopheresis and to summarize published data on its use as a prophylactic and therapy in heart transplant rejection.

Photostable Ruthenium(II) Isocyanoborato Luminophores and Their Use in Energy Transfer and Photoredox Catalysis.

Ruthenium(II) polypyridine complexes are among the most popular sensitizers in photocatalysis, but they face some severe limitations concerning accessible excited-state energies and photostability that could hamper future applications. In this study, the borylation of heteroleptic ruthenium(II) cyanide complexes with α-diimine ancillary ligands is identified as a useful concept to elevate the energies of photoactive metal-to-ligand charge-transfer (MLCT) states and to obtain unusually photorobust compounds suitable for thermodynamically challenging energy transfer catalysis as well as oxidative and reductive photoredox catalysis. B(C6F5)3 groups attached to the CN– ligands stabilize the metal-based t2g-like orbitals by ∼0.8 eV, leading to high 3MLCT energies (up to 2.50 eV) that are more typical for cyclometalated iridium(III) complexes. Through variation of their α-diimine ligands, nonradiative excited-state relaxation pathways involving higher-lying metal-centered states can be controlled, and their luminescence quantum yields and MLCT lifetimes can be optimized. These combined properties make the respective isocyanoborato complexes amenable to photochemical reactions for which common ruthenium(II)-based sensitizers are unsuited, due to a lack of sufficient triplet energy or excited-state redox power. Specifically, this includes photoisomerization reactions, sensitization of nickel-catalyzed cross-couplings, pinacol couplings, and oxidative decarboxylative C–C couplings. Our work is relevant in the greater context of tailoring photoactive coordination compounds to current challenges in synthetic photochemistry and solar energy conversion.

A geometrically exact continuum framework for light-matter interaction in photo-active polymers I. Variational setting

Molecular photo-switches as, e.g., azobenzene molecules allow, when embedded into a polymeric matrix, for photo-active polymer compounds responding mechanically when exposed to light of certain wavelength. Photo-mechanics, i.e. light-matter interaction in photo-active polymers holds great promise for, e.g., remote and contact-free activation of photo-driven actuators. In a series of earlier contributions, Oates et al. developed a successful continuum formulation for the coupled electric, electronic and mechanical problem capturing azobenzene polymer compounds, thereby mainly focussing on geometrically linearized kinematics [1, 2, 3]. Building on that formulation, we here explore the variational setting of a geometrically exact continuum framework based on Dirichlet’s and Hamilton’s principle as well as, noteworthy, Hamilton’s equations. Thereby, when treating the dissipative case, we resort to incremental versions of the various variational problems via suited incorporation of a dissipation potential. In particular, the Hamiltonian setting of geometrically exact photo-mechanics is up to now largely under-explored even for the energetic case, arguably since the corresponding Lagrangian is degenerate in Dirac’s sense. Moreover, in general, the Hamiltonian setting of dissipative dynamical systems is a matter of ongoing debate per se. In this contribution, by advocating a novel incremental version of the Hamiltonian setting exemplified for the dissipative case of photo-mechanics, we aim to also unify the variational approach to dissipative dynamical systems. Taken together, the variational setting of a geometrically exact continuum framework of photo-mechanics paves the way for forthcoming theoretical and numerical analyses.

Studying the "Rigid-Flexible" Properties of Polymeric Micelle Core-Forming Segments with a Hydrophobic Phthalocyanine Probe Using NMR and UV Spectroscopy.

The aim of the performed studies was to thoroughly examine the internal structure of self-assembled nanocarriers (i.e., polymeric micelles—PMs) by means of a hydrophobic phthalocyanine probe in order to identify the crucial features that are required to enhance the photoactive probe stability and reactivity. PMs of hydrophilic poly(ethylene glycol) and hydrophobic poly(ε-caprolactone) (PCL) or poly(d,l-lactide) (PDLLA) were fabricated and loaded with tetra tert-butyl zinc(II) phthalocyanine (ZnPc-t-but4), a multifunctional spectroscopic probe with a profound ability to generate singlet oxygen upon irradiation. The presence of subdomains, comprising “rigid” and “flexible” regions, in the studied block copolymers’ micelles as well as their interactions with the probe molecules, were assessed by various high-resolution NMR measurements [e.g., through-space magnetic interactions by the 1D NOE effect, pulsed field gradient spin-echo, and spin–lattice relaxation time (T1) techniques]. The studies of the impact of the core-type microenvironment on the ZnPc-t-but4 photochemical performance also included photobleaching and reactive oxygen species measurements. ZnPc-t-but4 molecules were found to exhibit spatial proximity effects with both (PCL and PDLLA) hydrophobic polymer chains and interact with both subdomains, which are characterized by different rigidities. It was deduced that the interfaces between particular subdomains constitute an optimal host space for probe molecules, especially in the context of photochemical stability, photoactivity (i.e., for significant enhancement of singlet oxygen generation rates), and aggregation prevention. The present contribution proves that the combination of an appropriate probe, high-resolution NMR techniques, and UV–vis spectroscopy enables one to gain complex information about the subtle structure of PMs essential for their application as nanocarriers for photoactive compounds, for example, in photodynamic therapy, nanotheranostics, combination therapy, or photocatalysis, where the micelles constitute the optimal microenvironment for the desired photoreactions.

Alkyl and aryl α-ketophosphonate derivatives as photoactive compounds targeting glutathione S-transferases

In this article, photoactive alkyl and aryl α-ketophosphonate derivatives were studied as inhibitors of glutathione S-transferases (GSTs). The α-ketophosphonate monoesters were synthesized by sodium iodide-induced dealkylation of corresponding phosphonate diesters. The compounds being inactive toward the enzyme without UV light were activated by irradiation at 365 nm which caused inhibition of GSTs from equine liver and human placenta with micromolar IC50 values. Hetaryl α-ketophosphonate monoesters can also be potential candidates for the UV-dependent enzyme targeting. Inhibitory potency of the phosphonate monoesters was comparable to that of free phosphonic acid. No effects were observed in case of dialkyl α-ketophosphonates. The light-induced effects of the inhibitors were found to be related to decrease in maximum velocity but not to Michaelis constants of the enzyme-catalyzed reaction. The kinetics of a decrease in enzyme activity was described by pseudo-first order rate constants dependent on inhibitor concentration. The calculated second order rate constants indicated that the alkyl α-ketophosphonate monoesters can exhibit higher potency in comparison with that of aryl or hetaryl phosphonate derivatives.

Development of Photoactive Supramolecular Devices and Machines

Among the various directions of the science of photoactive organic compounds, the design, creation, and study of photoactive supramolecular devices and machines are attracting special attention, since in this way it is possible to discover new approaches to construct complex hierarchical “smart” materials.

Synthesis and Photoactivated Toxicity of 2-Thiophenylfuranocoumarin Induce Midgut Damage and Apoptosis in Aedes aegypti Larvae.

Furanocoumarins are photoactive compounds derived from secondary plant metabolites. They possess many bioactivities, including antioxidative, anticancer, insecticidal, and bactericidal activities. Here, we designed a new scheme for synthesizing 2-arylfuranocoumarin derivatives by condensation, esterification, bromination, and Wittig reaction. We found that 2-thiophenylfuranocoumarin (Iy) had excellent photosensitive activity. Three Iy concentrations (LC25, LC50, and LC75) were used to treat the fourth instar larvae of Aedes aegypti (A. aegypti). The photoactivated toxicity, sublethal dose, mitochondrial dysfunction, oxidative stress level, intestinal barrier dysfunction, and apoptosis were studied. The results showed that Iy induced reactive oxygen species (ROS) production in midgut cells under ultraviolet light. Ultrastructural analysis demonstrated that mitochondria were damaged, and the activities of related enzymes were inhibited. Ultimately, Iy exposure led to excessive ROS production followed by the inhibition of antioxidant enzymes, including SOD, CAT, GPx, and GR, which diminished ROS elimination and escalated oxidative stress in midgut cells, aggravating the degree of oxidative damage in these cells. Histopathological changes were observed in the midgut, which led to intestinal barrier dysfunction. When the elimination of ROS was blocked and it accumulated in cells, apoptosis-related genes, including AeDronc, AeCaspase7, and AeCaspase8, were induced and activated. In addition, Iy affected the growth and development of A. aegypti at sublethal concentrations, and there was an obvious post-lethal effect. Thus, we found that Iy caused midgut damage and apoptosis in A. aegypti larvae under ultraviolet light, which preliminarily revealed the mode of action of Iy in A. aegypti.

Functionality of nanomaterials and its technological aspects - Used in preventing, diagnosing and treating COVID-19.

COVID-19 (Coronavirus) has severely affected the life of human beings since December 2019. Many difficulties are faced by human beings to prevent the spread of the corona virus. However, this unexpected evolution of COVID-19 has also thrown many challenges to scientists and researchers so as to develop technologies that can be used to combat COVID-19. In the effort to combat COVID-19, many research universities and academic laboratories are also contributing by developing many technologies like Facing masks, hand sanitizers, hand washing machines, etc., to control and prevent the spread of COVID-19 disease. The use of Nano-materials is proving to be very effective in prevention, detection and diagnosis of COVID-19. In this paper many such technologies that are used to combat COVID-19 are also discussed. Some of the technologies like the germ trap technology used in face masks and hoods are also discussed. The use of nano-coatings, nano materials like graphene and carbon nano materials is playing a key role in preventing the spread of the virus. Antimicrobial nano-materials like silver nanoparticles are also effectively contributing to preventing the spread of the virus. Nano bio-sensors and gold nanoparticles are used in RT-PCR (Reverse transcription polymerase chain reaction) testing devices which are used for detection of coronavirus. The use of many nano chemicals and compounds has helped in making vaccines and anti-viral drugs that are today showing a way to safeguard human beings against the attack of this deadly virus.

Study of the photoinduced transformations of sertraline in aqueous media

In the present study, the photoinduced degradation of the antidepressant drug sertraline under artificial solar radiation was examined. Photolysis was studied under different experimental conditions to explore its photolytic fate in the aqueous environment. Photolytic degradation kinetics were carried out in ultrapure water, wastewater effluent, as well as in the presence of dissolved organic matter (humic acids), bicarbonate and nitrate ions which enabled their assessment on sertraline photo-transformation. The reaction of sertraline with photoactive compounds accelerated sertraline transformation in comparison with direct photolysis. Moreover, TiO2-mediated photocatalytic degradation of sertraline was investigated, and focus was placed on the identification of by-products. As expected, photocatalysis was extremely effective for sertraline degradation. Photocatalytic degradation proceeded through the formation of forty-four transformation products identified by HPLC-HRMS and after 240 min of irradiation total mineralization was achieved. Microtox bioassay (Vibrio fischeri) was employed to assess the ecotoxicity of the photocatalysis-treated solutions and results have indicated that sertraline photo-transformation proceeds through the formation of toxic compounds.

Turning Photons into Drugs: Phthalocyanine-Based Photosensitizers as Efficient Photoantimicrobials.

One of the most promising alternatives for treating bacterial infections is antimicrobial photodynamic therapy (aPDT), making the synthesis and application of new photoactive compounds called photosensitizers (PS) a dynamic research field. In this regard, phthalocyanine (Pc) derivatives offer great opportunities due to their extraordinary light‐harvesting and tunable electronic properties, structural versatility, and stability. This Review, rather than focusing on synthetic strategies, intends to overview current progress in the structural design strategies for Pcs that could achieve effective photoinactivation of microorganisms. In addition, the Review provides a concise look into the recent developments and applications of nanocarrier‐based Pc delivery systems.

Accessing Excited State Molecular Vibrations by Femtosecond Stimulated Raman Spectroscopy.

Excited state vibrations are crucial for determining the photophysical and photochemical properties of molecular compounds. Stimulated Raman scattering can coherently stimulate and probe molecular vibrations with optical pulses, but it is generally restricted to ground state properties. Working under resonance conditions enables cross-section enhancement and selective excitation to a targeted electronic level but is hampered by an increased signal complexity due to the presence of overlapping spectral contributions. Here, we show how detailed information about ground and excited state vibrations can be disentangled by exploiting the relative time delay between Raman and probe pulses to control the excited state population, combined with a diagrammatic formalism to dissect the pathways concurring with the signal generation. The proposed method is then exploited to elucidate the vibrational properties of the ground and excited electronic states in the paradigmatic case of cresyl violet. We anticipate that the presented approach holds the potential for selective mapping of the reaction coordinates pertaining to transient electronic stages implied in photoactive compounds.

Association between Citrus Consumption and Melanoma Risk in the NIH-AARP Diet and Health Study

It has been hypothesized that consumption of citrus, a group of foods particularly rich in a class of photoactive compounds known as furocoumarins, may increase the risk of malignant melanoma. However, this hypothesis has not been rigorously studied in a general sample of US men and women. This study examined the relationship between citrus intake and melanoma risk in subjects of the NIH-AARP Diet and Health Study. Among 388,467 adults, 3,894 melanoma cases were identified during a median follow-up of 15.5 years. After adjustment for relevant potential confounders, total citrus consumption was not significantly associated with melanoma risk in this cohort. Among those with higher estimated exposure to ultraviolet radiation, and among those aged 60+ years at baseline, there were significant trends toward increased melanoma risk associated with whole citrus fruit consumption (P trends = 0.01 and 0.02, respectively), but the hazard ratios of the top consumers (2+ cups per week) vs. nonconsumers were nonsignificant. Further research is needed to explore associations of citrus with melanoma risk among older adults and those with high sun exposure.

Daylight-Active Cellulose Nanocrystals Containing Anthraquinone Structures.

Antimicrobial and antiviral materials have attracted significant interest in recent years due to increasing occurrences of nosocomial infections and pathogenic microbial contamination. One method to address this is the combination of photoactive compounds that can produce reactive oxygen species (ROS), such as hydrogen peroxide and hydroxyl radicals to disinfect microbes, with carrier materials that meet the application requirements. Using anthraquinone (AQ) and cellulose nanocrystals (CNCs) as the photoactive and carrier components, respectively, this work demonstrated the first covalent incorporation of AQ onto CNCs. The morphology and the photoactive properties were investigated, revealing the structural integrity of the CNCs and the high degree of photoactivity of the AQ-CNC materials upon UVA exposure. The AQ-CNCs also exhibited an unexpected persistent generation of ROS under darkness, which adds advantages for antimicrobial applications.

Water-soluble tetra-cationic porphyrins display virucidal activity against Bovine adenovirus and Bovine alphaherpesvirus 1.

Porphyrins are photoactive compounds that can absorb the energy of light and transfer it to oxygen molecules, producing reactive oxygen species (ROS). Once produced, ROS may alter biological molecules and cellular mechanisms, leading to cell apoptosis or inactivation of microorganisms, such as bacteria, fungi, and viruses. Therefore, the objective of this study was to evaluate the in vitro virucidal activity of six tetra-cationic porphyrins against two bovine viruses (Bovine alphaherpesvirus 1, BoHV-1, enveloped; and Bovine adenovirus, BAV, non-enveloped). For this, viral suspensions were incubated with each porphyrin (H2TMeP, ZnTMeP, and CuTMeP at 4.0 μM, NiTMeP at 5.0 μM, and CoClTMeP and MnClTMeP at 1.0 μM) and exposed to white-light irradiation for 0, 60, 120, and 180 min (BAV) or 0, 30, 60, 90, and 120 min (BoHV-1). Then, the remaining viral titers were determined by limiting dilution and compared with the control (virus + porphyrins without light exposition). The porphyrins H2TMeP and ZnTMeP showed the highest virucidal activity against both viruses. ZnTMeP inactivated BoHV-1 after 30 min of photoactivation and H2TMeP after 60 min. The BAV was photo-inactivated by both porphyrins at 180 min of white-light exposition. CuTMeP, NiTMeP, and CoClTMeP porphyrins had weak virucidal activity against BoHV-1 and MnClTMeP showed no virucidal activity against both viruses. These results indicated that free-base H2TMeP and ZnTMeP porphyrins present virucidal activity against non-enveloped and enveloped viruses, opening the possibility for their use to inactivate viruses on surfaces, biological substrates, and solutions.

Synthesis and characterization of cyclen cored photoactive star compounds and their Cu(I) and Cu(II) complexes. Effect of the valence and ligand size on their molar extinction coefficient

Two novel cyclen-cored star compounds were functionalized with pyrene moieties on the periphery and used as ligands to produce the corresponding Cu(I) and Cu(II) complexes. The complexation of both ligands was comparatively studied by UV–vis spectroscopy. The Cu(I) and Cu(II) complexes were characterized in chloroform solution by different spectroscopic techniques. These studies suggested that the Cu(I) is coordinated to the four nitrogens of the cyclen ring exhibiting a tetrahedral conformation, while the Cu(II) complexes are coordinated in a similar manner to the nitrogen atoms of the cyclen ligand and to one or two of the carbonyl groups of the dendrons, in a distorted square pyramidal and octahedral geometries. The coordination environment generated species with enhanced photosensitive properties compared to the free ligands, due to the stereochemistry of the complexes induced by the copper.

Development of DNA polymer films as a drug delivery system for the treatment of oral cancer.

DNA polymer films (DNA-PFs) hold promise for use in drug delivery systems (DDS). In this study, the growth pattern of oral squamous cell carcinoma (OSCC) cells was evaluated on DNA-PFs incorporated with a photoactive compound chlorine aluminum phthalocyanine (DNA-PFs-AlClPc) and the efficacy of DNA-PFs-AlClPc as a DDS for photodynamic therapy (PDT) for the treatment of mucosal cancer. Flow cytometry was used to evaluate cell viability following application of DNA-PFs-AlClPc during PDT; the results demonstrated a positive response to photo stimulation within the range of light doses used (300, 600, and 1200mJ/cm2). Reduced viability and increased cell death were observed with increasing doses than in the controls. As expected, the viability was reduced by more than 30% at the highest dose (1200mJ/cm2). Flow cytometry revealed that the main mechanism of cell death induction was apoptosis (early and late apoptosis). These results demonstrate the potential of applying DNA-PFs-AlClPc as a DDS for other active molecules in the treatment of other pathologies. Furthermore, this system allows other drugs to be associated with DNA-PFs, indicating the potential use of this nanostructure in novel ways for the treatment of different neoplasms, such as oral cancer. Additionally, DNA nanostructured films may be used to support cell growth and subsequently as a "curative material" incorporated with an active or photoactive compound that can induce tissue regeneration. Graphical abstract .

The Malleable Excited States of Benzothiadiazole Dyes and Investigation of their Potential for Photochemical Control

AbstractA new design strategy to control the efficiency of a photocleavage reaction based on changing the nature of the excited state is presented. A novel class of photoactive compounds has been synthesized by combining the classical o‐nitrobenzyl scaffold with an environmentally sensitive dye, 4‐amino‐nitrobenzothiazole. Irradiation in a polar solvent led to an excited state that was inoperative for photochemistry whereas excitation in a nonpolar solvent led to an excited state that was photochemically active. While our design hypothesis tests true for the on/off control of a photochemical process, an alternative photochemical ring‐opening of the heterocycle appears to be the preferred process in contrast to the intended photocleavage process.

CASPT2 Potential Energy Curves for NO Dissociation in a Ruthenium Nitrosyl Complex.

Ruthenium nitrosyl complexes are fascinating photoactive compounds showing complex photoreactivity, such as N→O linkage photoisomerism and NO photorelease. This dual photochemical behavior has been the subject of many experimental studies in order to optimize these systems for applications as photoswitches or therapeutic agents for NO delivery. However, despite recent experimental and computational studies along this line, the underlying photochemical mechanisms still need to be elucidated for a more efficient design of these systems. Here, we present a theoretical contribution based on the calculations of excited-state potential energy profiles for NO dissociation in the prototype trans-[RuCl(NO)(py)4]2+ complex at the complete active space second-order perturbation theory (CASPT2). The results point to a sequential two-step photon absorption photorelease mechanism coupled to partial photoisomerization to a side-on intermediate, in agreement with previous density functional theory calculations.

Interaction of CdTe-MPA quantum dots with meso-tetra methyl pyridyl porphyrin. Charge transfer complex formation

The unique characteristics of quantum dots (QD), such as an intensive and narrow luminescence spectrum, broad and intense absorption spectrum and high chemical and photostability, make them promising for applications in various fields, including in medicine as probes in the cancer luminescence diagnostics. The effective light absorption by QD in a wide spectral region allows their use as an antenna to accumulate light energy and transfer this energy to other photoactive compounds (photosensitizers, PS). A charge transfer complex between QD and PS can be formed as well. This can change spectral and energetic characteristics of the complex components, thus affecting their efficiency in applications. In this work we demonstrate the formation of a charge transfer complex between CdTe QD functionalized by 3-Mercaptopropionic Acid (3-MPA) and meso-tetra methyl pyridyl porphyrin (TMPyP) in water solutions and present its excited state spectral and temporal characteristics. The complexation constant was Kb = 5.5 ± 0.5 M−1. On the base of the QD luminescence quenching at complexation we propose the network structure of the TMPyP-QD complex.

Anthraquinone encapsulation into polymeric nanocapsules as a new drug from biotechnological origin designed for photodynamic therapy.

Photodynamic therapy has been applied for the treatment of many diseases, especially skin diseases. However, poor aqueous solubility and toxicity of some photosensitizer drugs are the main disadvantages for their direct clinical applications. Thus, biotechnology and nanotechnology are important tools in the development of new ways of obtaining photoactive compounds that are biocompatible. We investigated the potential of a new nanostructured photosensitizer, an anthraquinone derivative produced by biotechnological process; then we associated nanotechnology to obtain a nanostructured anthraquinone active molecule. For this, it was prepared a classical nanocapsule formulations containing poly(lactide-co-glycolide) (PLGA) coating for encapsulation of anthraquinone derivative. These formulations were characterized by their physicochemical, morphological, photophysical properties, and stability. We performed in vitro biocompatibility and photodynamic activity assays of free and nanostructured anthraquinone. Nanocapsule formulations containing anthraquinone derivative showed a nanometric profile with particle size around 250 nm, negative zeta potential around -30 mV, and partially monodisperse. Besides that, characteristic spherical morphology of nanocapsules and homogeneous particle surface were observed by AFM analyses. The in vitro biocompatibility assay showed absence of cytotoxicity for all tested RD/NC concentrations and also for unloaded/NC in NIH3T3 cells. In vitro photoactivation assay using NIH3T3 cells showed that nanocapsules promoted greater drug uptake by NIH3T3 cells, around of 87%, of cell death compared to free drug showed around 48% of cell death. The anthraquinone derivative showed potential for use in PDT. Besides the association with nanocapsules improved cell uptake of photosensitizer resulting in increased cell death compared to free anthraquinone.