Light-mediated Activation Research Articles

Unveiling Na2-Eosin Y-Catalyzed and Water-Assisted Visible-Light Activation of Oxygen Molecules for the Dicarbonylation of Pyrazole Amines.

A novel approach employing visible light-mediated activation of triplet oxygen molecules has been established. The reaction occurs at room temperature between pyrazole amine and phenylglyoxal monohydrate in the presence of Na2-eosin Y. Water played the dual role of solvent and reagent/additive. Photoactivation of triplet oxygen species was used to demonstrate the initiation of the hydrogen atom transfer (HAT) process. The conversion of the reaction mixture was found to be dependent on the amount of water present. Control experiments confirmed the importance of light, the photocatalyst, oxygen, the base, and water. The process tolerated various substitutions in both pyrazole amine and phenylglyoxal derivatives, enabling the synthesis of various dicarbonylpyrazole amines 15 and pyrazolooxazine derivatives 16 in moderate to good yields. 2 equiv of phenylglyoxal 10 gave a different reaction pathway, yielding highly diastereoselective pyrazolooxazine derivatives, confirmed by X-ray diffraction analysis. Collectively, this sustainable and environmentally friendly synthetic technique offers a promising method for the efficient preparation of pyrazole-based heterocyclic compounds. The high regioselectivity observed during the formation of trans-tetrahydropyrazolo[3,4-d][1,3]oxazine has been clarified through computational methods. These investigations emphasize the underlying factors and mechanisms that encourage the formation of this specific product, providing valuable insights into the reaction's selectivity and efficiency.

Shedding Light on Cardiac Excitation: In Vitro and In Silico Analysis of Native Ca2+ Channel Activation in Guinea Pig Cardiomyocytes Using Organic Photovoltaic Devices.

This study aims to explore the potential of organic electrolytic photocapacitors (OEPCs), an innovative photovoltaic device, in mediating the activation of native voltage-gated Cav1.2 channels (ICa,L) in Guinea pig ventricular cardiomyocytes. Whole-cell patch-clamp recordings were employed to examine light-triggered OEPC mediated ICa,L activation, integrating the channel's kinetic properties into a multicompartment cell model to take intracellular ion concentrations into account. A multidomain model was additionally incorporated to evaluate effects of OEPC-mediated stimulation. The final model combines external stimulation, multicompartmental cell simulation, and a patch-clamp amplifier equivalent circuit to assess the impact on achievable intracellular voltage changes. Light pulses activated ICa,L, with amplitudes similar to voltage-clamp activation and high sensitivity to the L-type Ca2+ channel blocker, nifedipine. Light-triggered ICa,L inactivation exhibited kinetic parameters comparable to voltage-induced inactivation. OEPC-mediated activation of ICa,L demonstrates their potential for nongenetic optical modulation of cellular physiology potentially paving the way for the development of innovative therapies in cardiovascular health. The integrated model proves the light-mediated activation of ICa,L and advances the understanding of the interplay between the patch-clamp amplifier and external stimulation devices. Treating cardiac conduction disorders by minimal-invasive means without genetic modifications could advance therapeutic approaches increasing patients' quality of life compared with conventional methods employing electronic devices.

Imaging bioluminescence by detecting localized haemodynamic contrast from photosensitized vasculature.

Bioluminescent probes are widely used to monitor biomedically relevant processes and cellular targets in living animals. However, the absorption and scattering of visible light by tissue drastically limit the depth and resolution of the detection of luminescence. Here we show that bioluminescent sources can be detected with magnetic resonance imaging by leveraging the light-mediated activation of vascular cells expressing a photosensitive bacterial enzyme that causes the conversion of bioluminescent emission into local changes in haemodynamic contrast. In the brains of rats with photosensitized vasculature, we used magnetic resonance imaging to volumetrically map bioluminescent xenografts and cell populations virally transduced to express luciferase. Detecting bioluminescence-induced haemodynamic signals from photosensitized vasculature will extend the applications of bioluminescent probes.

Visible light-mediated activation of periodate for bisphenol A degradation in the presence of Fe3+ and gallic acid at neutral pH

The current study demonstrates, for the first time, the effectiveness of an innovative visible light (VL) photo-Fenton like system using periodate (PI) mediated by Fe3+ and gallic acid (GA) for bisphenol A (BPA) elimination at neutral pH. The promotion of VL irradiation and GA on the Fe2+/Fe3+ cycle in the system allowed the VL/GA/Fe3+/PI system to exhibit excellent performance for BPA removal. Complete degradation of BPA was carried out in the VL/GA/Fe3+/PI process after 30 min reaction under the optimum conditions (0.10 mM Fe3+, 0.10 mM GA, 1 mM PI, and initial pH 7.0). Electron paramagnetic resonance analysis and quenching tests confirmed that the singlet oxygen, iodate radical, and hydroxyl radical were primarily involved in the elimination of BPA with minor contribution from superoxide anion radical and high-valent iron species (Fe4+ and Fe5+). BPA abatement was slightly inhibited by the addition of Cl−, NO3−, and SO42−, whereas the addition of HCO3− obviously hindered this process. Notably, Huimic acid dramatically expedited BPA decomposition. Besides, the VL/GA/Fe3+/PI process demonstrated remarkable removal efficiency over a broad range of initial pH values (3.01–8.97). Meanwhile, based on the eight identified intermediates, the possible degradation pathways of BPA were predicted. The phytotoxicity test concluded that a decrease in toxicity of the degraded intermediates to the growth of radish seed compared to BPA. In addition, the VL/GA/Fe3+/PI system demonstrated favorable potential for application in different actual water matrices. Moreover, efficient and simultaneous abatement of various organic contaminants by the GA/Fe3+/PI process was success accomplished under natural solar light or VL. Consequently, all results implied that the VL/GA/Fe3+/PI process might be a perspective technique for the treatment of organic contaminants.

Photonanozyme with Light Mediated Activity.

Since the discovery that Fe3 O4 nanoparticle has intrinsic natural peroxidase-like activity by Yan et al in 2007, mimicking native enzymes via nano-engineering (named as nanozyme) pays a new avenue to bypass the fragility and recyclability of natural enzymes and thus expedites the biocatalysis in multidisciplinary applications. In addition, the high programmability and structural stability attributes of nanozyme afford the ease of coupling with electromagnetic waves of different energies, providing great opportunities to construct photo-responsive nanozyme under user-defined electromagnetic waves, which is known as photo-nanozyme. In this concept, we aim to providing a summary of how electromagnetic waves with varying wavelengths can serve as external stimuli to induce or enhance the biocatalytic performance of photo-nanozymes, thereby offering fascinating functions that cannot be achieved by pristine nanozyme.

A DNA-based nanodevice for near-infrared light-controlled drug release and bioimaging

DNA-based nanostructures have shown curative potential in drug delivery and anti-tumor therapy. However, the applications of such systems are limited by the lack of precise control over the space and duration of drug release. Here, we report a near-infrared (NIR) light-guided DNA nanodevice that enables controlled drug release for precise tumor imaging and therapy. The DNA nanodevice is constructed by engineering GC-rich DNA duplexes with an ultraviolet (UV) light labile moiety and further modification onto the surface of upconversion nanoparticles (UCNPs). The chemotherapeutic drug (doxorubicin, Dox) is intercalated into the GC motif of DNA duplexes, where the fluorescence signal of Dox is markedly quenched. Upon NIR light irradiation, the UCNPs acting as energy transducers emit UV light that can break the photolabile moiety in DNA duplexes, resulting in the controlled release of Dox and recovery of their fluorescence signal. We present that this DNA nanodevice is not only able to selectively induce tumor cells apoptosis via NIR light-mediated activation, but also enables in situ imaging and monitoring of drug release. Therefore, this modular strategy opens a window for remotely controlled drug delivery.

Massively parallel genomic perturbations with multi-target CRISPR interrogates Cas9 activity and DNA repair at endogenous sites

Here we present an approach that combines a clustered regularly interspaced short palindromic repeats (CRISPR) system that simultaneously targets hundreds of epigenetically diverse endogenous genomic sites with high-throughput sequencing to measure Cas9 dynamics and cellular responses at scale. This massive multiplexing of CRISPR is enabled by means of multi-target guide RNAs (mgRNAs), degenerate guide RNAs that direct Cas9 to a pre-determined number of well-mapped sites. mgRNAs uncovered generalizable insights into Cas9 binding and cleavage, revealing rapid post-cleavage Cas9 departure and repair factor loading at protospacer adjacent motif-proximal genomic DNA. Moreover, by bypassing confounding effects from guide RNA sequence, mgRNAs unveiled that Cas9 binding is enhanced at chromatin-accessible regions, and cleavage by bound Cas9 is more efficient near transcribed regions. Combined with light-mediated activation and deactivation of Cas9 activity, mgRNAs further enabled high-throughput study of the cellular response to double-strand breaks with high temporal resolution, revealing the presence, extent (under 2 kb) and kinetics (~1 h) of reversible DNA damage-induced chromatin decompaction. Altogether, this work establishes mgRNAs as a generalizable platform for multiplexing CRISPR and advances our understanding of intracellular Cas9 activity and the DNA damage response at endogenous loci.

Conjugates of Porphyrinoid-Based Photosensitizers with Cytotoxic Drugs: Current Progress and Future Directions toward Selective Photodynamic Therapy.

Photodynamic therapy (PDT) is a treatment modality where light-mediated activation of photosensitizers in a patient's body leads to the generation of cytotoxic reactive oxygen species (ROS), eliminating cancer cells. One direction that has been firmly established over past years is the conjugation of photosensitizers with various molecules that demonstrate their own cytotoxic activity. As a result, improved selectivity and treatment outcomes are observed compared to those of unconjugated drugs. The attractiveness of such an approach is due to the variability of cytotoxic warheads and specific linkers available for the construction of conjugates. In this review, we summarize and analyze data concerning these inventions with the ultimate goal to find a promising conjugation partner for a porphyrinoid-based photosensitizer. The current challenges toward successful conjugation are also outlined and discussed. We hope that this review will motivate researchers to pay closer attention to conjugates and possibilities hidden in these molecules for the PDT of cancer.

UV photocatalytic activity of titanium dioxide (TiO2) surface contaminated with bacterial biofilm: Implications for photo-restoration of osteoconductivity

Ultraviolet (UV) light-mediated activation of titanium dioxide (TiO2) cleans the surface microenvironment through photocatalysis, but it is unknown whether this occurs when TiO2 surfaces is contaminated with bacterial biofilms. We therefore formed bacterial biofilms on TiO2 surfaces through culture with oral microorganisms from rats, which were subsequently exposed to high-intensity broadband UV light for 12 min. Osteoblast attachment, proliferation, and phenotypes were significantly compromised on biofilm-contaminated TiO2 surfaces, but UV treatment restored these biological activities to native baselines of TiO2 surfaces. The strength of bone-implant integration was 18.3 N for original implants, 1.5 N for biofilm-contaminated implants, and 30.5 N for biofilm-contaminated/UV-treated implants in a rat femur model after two weeks of healing. Histologically, there was limited, fragmented bone formation around biofilm-contaminated implants separated by thick fibrous tissue, while biofilm-contaminated/UV-treated implants induced robust bone formation with extensive direct bone-implant contact. Lipopolysaccharide (LPS) deposited on biofilm-contaminated TiO2 surfaces which was decomposed and removed by UV treatment. Notably, biofilm-contaminated TiO2 surfaces became superhydrophilic after UV treatment despite the persistence of carbon and nitrogen compounds, and UV treatment significantly restored the surface morphology of the innate titanium on the biofilm-contaminated TiO2 surfaces. In summary, bacterial biofilm severely compromised titanium osteoconductivity, but treatment of contaminated titanium with UV light significantly restored osteoconductivity through substantially decreased accumulation of carbon, nitrogen, and LPS; the re-emergence of micro-topography; and the induction of superhydrophilicity, paving the way for photoenergy-mediated debridement of TiO2 surface for clinical benefit.

UV-Light-Driven Enhancement of Peroxidase-Like Activity of Mg-Aminoclay-Based Fe3O4/TiO2 Hybrids for Colorimetric Detection of Phenolic Compounds

Light-activated nanozymes possess several advantages, such as light-mediated activity regulation, utilization of molecular oxygen as a green oxidant, and highly enhanced activity; however, the types of light-activated nanozymes are still limited. In this study, we found that Mg aminoclay-based Fe3O4/TiO2 hybrids (MgAC-Fe3O4/TiO2) exhibited peroxidase-like catalytic activity to catalyze the oxidation of the peroxidase substrate 2,2′-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS) in the presence of H2O2, which was significantly enhanced under ultraviolet (UV)-light irradiation. Compared with MgAC-Fe3O4 and MgAC-TiO2, MgAC-Fe3O4/TiO2 showed around three-fold enhancement in the absorption intensity corresponding to the oxidized ABTS under UV-light irradiation, presumably due to the synergistic effect between Fe3O4 and TiO2, thereby facilitating photocatalytic electron transfer during the catalytic action. In addition, the MgAC-Fe3O4/TiO2 showed vivid stability enhancement in wide range of pH and temperature values compared with natural peroxidase. The UV-light-driven MgAC-Fe3O4/TiO2-based system was successfully applied for the colorimetric detection of phenolic compounds, including pyrocatechol and resorcinol, in a dynamic linear range of 0.15–1.30 mg/mL with a limit of detection as low as 0.1 mg/mL. Further, the system could successfully determine the phenolic compounds in spiked tap water, and thus, it can be used for practical applications. We believe that the UV-light-driven enhancement in the peroxidase-like catalytic performances highlights the potential of MgAC-Fe3O4/TiO2 for detecting phenolic compounds as well as other clinically and environmentally important substances.

Photochemical and Photobiological Properties of Pyridyl-pyrazol(in)e-Based Ruthenium(II) Complexes with Sub-micromolar Cytotoxicity for Phototherapy.

The discovery of new light-triggered prodrugs based on ruthenium (II) complexes is a promising approach for photoactivated chemotherapy (PACT). The light-mediated activation of “strained” Ru(II) polypyridyl complexes resulted in ligand release and produced a ligand-deficient metal center capable of forming covalent adducts with biomolecules such as DNA. Based on the strategy of exploiting structural distortion to activate photochemistry, biologically active small molecules were coordinated to a Ru(II) scaffold to create light-triggered dual-action agents. Thirteen new Ru(II) complexes with pyridyl-pyrazol(in)e ligands were synthesized, and their photochemical reactivity and anticancer properties were investigated. Isomeric bidentate ligands were investigated, where “regular” ligands (where the coordinated nitrogens in the heterocycles are linked by C–C atoms) were compared to “inverse” isomers (where the coordinated nitrogens in the heterocycles are linked by C–N atoms). Coordination of the regular 3-(pyrid-2-yl)-pyrazol(in)es to a Ru(II) bis-dimethylphenanthroline scaffold yielded photoresponsive compounds with promising photochemical and biological properties, in contrast to the inverse 1-(pyrid-2-yl)-pyrazolines. The introduction of a phenyl ring to the 1N-pyrazoline cycle increased the distortion in complexes and improved ligand release upon light irradiation (470 nm) up to 5-fold in aqueous media. Compounds 1–8, containing pyridyl-pyrazol(in)e ligands, were at least 20–80-fold more potent than the parent pyridyl-pyrazol(in)es, and exhibited biological activity in the dark, with half-maximal inhibitory concentration (IC50) values ranging from 0.2 to 7.6 μM in the HL60 cell line, with complete growth inhibition upon light irradiation. The diversification of coligands and introduction of a carboxylic acid into the Ru(II) complex resulted in compounds 9–12, with up to 146-fold improved phototoxicity indices compared with complexes 1–8.

Sulfated and Oxygenated Imidazoline Derivatives: Synthesis, Antioxidant Activity and Light-Mediated Antibacterial Activity.

Imidazoline derivatives with different exocyclic substituents were simply prepared from common starting materials. The procedures were carried out in an eco-friendly manner. The antioxidant activity of these derivatives was explored by different experimental assays, such as ABTS.+ and DPPH. scavenging assay, as well as reducing power assay. The structural differences are discussed in terms of the results. Sulfur analogs showed higher antioxidant activity than their oxygenated counterparts. The same tendency was observed in microbiological studies, in which the same imidazoline compounds were assayed for light-mediated activity against of Staphylococcus aureus and Escherichia coli strains. A light-enhanced activity was observed for almost all the sulfated imidazolines after exposure to UV-A (400-320 nm) light.

Ultraviolet light-mediated activation of persulfate for the degradation of cobalt cyanocomplexes

The ultraviolet light activation of persulfate (PS) was evaluated for the degradation of cobalt cyanocomplexes, which are considered as some of the most recalcitrant compounds present in mining wastewater. The influence of the solution pH (11 and 13), initial concentration of PS (0.1, 0.3, 0.5, 0.7 and 0.9 g/L), dissolved oxygen and initial concentration of contaminant were evaluated. Photolysis results showed that CoCN63- is photosensitive to UVC radiation, while the activation of PS by alkaline pH does not contribute to the degradation of the cyanocomplex. There was no presence of CN- at both solution pH values using UVC/PS. But at pH 13, the degradation of cobalt cyanocomplexes and the pseudo-first-order rate constant increased. This was attributed to the effective conversion of SO4•- to HO• and to the increase in the oxidative photolysis of PS at high pH. Additional tests demonstrated better performance of UVC/PS in the absence of oxygen which may be caused by the quenching effect of O2 to the higher energy excited state of the cyanocomplex that must be reached to initiate degradation reactions. Increasing the initial concentration of CoCN63- will increase the amount of Co removed but it represents the higher specific energy consumption.

Preclinical and Clinical Evidence of Immune Responses Triggered in Oncologic Photodynamic Therapy: Clinical Recommendations.

Photodynamic therapy (PDT) is an anticancer strategy utilizing light-mediated activation of a photosensitizer (PS) which has accumulated in tumor and/or surrounding vasculature. Upon activation, the PS mediates tumor destruction through the generation of reactive oxygen species and tumor-associated vasculature damage, generally resulting in high tumor cure rates. In addition, a PDT-induced immune response against the tumor has been documented in several studies. However, some contradictory results have been reported as well. With the aim of improving the understanding and awareness of the immunological events triggered by PDT, this review focuses on the immunological effects post-PDT, described in preclinical and clinical studies. The reviewed preclinical evidence indicates that PDT is able to elicit a local inflammatory response in the treated site, which can develop into systemic antitumor immunity, providing long-term tumor growth control. Nevertheless, this aspect of PDT has barely been explored in clinical studies. It is clear that further understanding of these events can impact the design of more potent PDT treatments. Based on the available preclinical knowledge, recommendations are given to guide future clinical research to gain valuable information on the immune response induced by PDT. Such insights directly obtained from cancer patients can only improve the success of PDT treatment, either alone or in combination with immunomodulatory approaches.

Melanopsin Retinal Ganglion Cells Regulate Cone Photoreceptor Lamination in the Mouse Retina

Newborn neurons follow molecular cues to reach their final destination, but whether early life experience influences lamination remains largely unexplored. As light is among the first stimuli to reach the developing nervous system via intrinsically photosensitive retinal ganglion cells (ipRGCs), we asked whether ipRGCs could affect lamination in the developing mouse retina. We show here that ablation of ipRGCs causes cone photoreceptors to mislocalize at different apicobasal positions in the retina. This effect is partly mediated by light-evoked activity in ipRGCs, as dark rearing or silencing of ipRGCs leads a subset of cones to mislocalize. Furthermore, ablation of ipRGCs alters the cone transcriptome and decreases expression of the dopamine receptor D4, while injection of L-DOPA or D4 receptor agonist rescues the displaced cone phenotype observed in dark-reared animals. These results show that early light-mediated activity in ipRGCs influences neuronal lamination and identify ipRGC-elicited dopamine release as a mechanism influencing cone position.

Temporal control of growth factor‐mediated signaling pathways during cell differentiation and Xenopus embryonic development

Growth factor‐mediated signaling pathways regulate a wide‐spectrum of cellular functions such as survival, proliferation, differentiation, and apoptosis. Different growth factors typically trigger the activation of the same set of downstream signaling pathways which includes the mitogen activated protein kinase (MAPK), phosphoinositide 3‐kinase (PI3K)‐AKT, and phospholipase C (PLC) pathways Evidence suggests that precise spatiotemporal regulation of these signaling pathways is involved in generating diverse cellular outcomes. Although conventional genetic and pharmacological approaches have helped us understand different aspects of signaling pathways, a quantitative delineation of their signaling kinetics is pending due to a lack of tools that allow for precise temporal control of these pathways. Non‐neuronal optogenetics, an emerging technique that utilizes light to control intracellular signaling pathways, is a remarkable tool to help achieve this goal. Here, we introduce a bicistronic optogenetic system which we recently developed in our laboratory to achieve temporal control of the MAPK pathway. This tool uses the photoactivatable protein cryptochrome 2 (CRY2) and the N‐terminal domain of cryptochrome‐interacting basic‐helix‐loop‐helix (CIBN) from Arabidopsis thaliana. This novel system allows reversible, light‐mediated activation of the MAPK signaling pathway in intact mammalian cells as well as in developing Xenopus laevis embryos. In PC12 neuronal cells, light‐controlled, intermittent MAPK activity reveals a memory effect in light‐induced neurite outgrowth. In Xenopus embryos, developmental stage‐specific MAPK activation further reveals that this pathway can reprogram cell fate after a crucial time window when germ layers are specified. Our strategy can be generalized to control other kinase pathways with a similar activation mechanism. Results from our research will help resolve intracellular mechanisms of growth factor‐mediated signal transduction during cell differentiation and embryonic development.Support or Funding InformationKai Zhang, Department of Biochemistry, University of Illinois Urbana‐ChampaignThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

One-Pot Amide Bond Formation from Aldehydes and Amines via a Photoorganocatalytic Activation of Aldehydes.

A mild, one-pot, and environmentally friendly synthesis of amides from aldehydes and amines is described. Initially, a photoorganocatalytic reaction of aldehydes with di-isopropyl azodicarboxylate leads to an intermediate carbonyl imide, which can react with a variety of amines to afford the desired amides. The initial visible light-mediated activation of a variety of monosubstituted or disubstituted aldehydes is usually fast, occurring in a few hours. Following the photocatalytic reaction, addition of the primary amine at room temperature or the secondary amine at elevated temperatures leads to the corresponding amide from moderate to excellent yields without epimerization. This methodology was applied in the synthesis of Moclobemide, a drug against depression and social anxiety.

An elastic second skin.

We report the synthesis and application of an elastic, wearable crosslinked polymer layer (XPL) that mimics the properties of normal, youthful skin. XPL is made of a tunable polysiloxane-based material that can be engineered with specific elasticity, contractility, adhesion, tensile strength and occlusivity. XPL can be topically applied, rapidly curing at the skin interface without the need for heat- or light-mediated activation. In a pilot human study, we examined the performance of a prototype XPL that has a tensile modulus matching normal skin responses at low strain (<40%), and that withstands elongations exceeding 250%, elastically recoiling with minimal strain-energy loss on repeated deformation. The application of XPL to the herniated lower eyelid fat pads of 12 subjects resulted in an average 2-grade decrease in herniation appearance in a 5-point severity scale. The XPL platform may offer advanced solutions to compromised skin barrier function, pharmaceutical delivery and wound dressings.

Light-mediated antibacterial activity of Lippia origanoides H.B.K. in vitro

An ethanol extract and different partition fractions obtained from Lippia origanoides H.B.K. were assayed for light-mediated activity against strains of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Identical assays were conducted with and without exposure to UV-A (400-315 nm) light to test for light enhanced activity. The ethanol extract and dichloromethane fraction showed light-mediated activity against the S. aureus strain, but not against the E. coli strain. The dichloromethane fraction was more active than the ethanol extract. Naringenin did not display light-mediated activity against the tested bacteria, indicating that the light-mediated antimicrobial activity of the dichloromethane fraction is not due to its major component. The results represent the first report of light-mediated antimicrobial activity of Lippia origanoides and show that its phytochemicals could be used as light-mediated antimicrobial agents.

Feedback regulation of cone cyclic nucleotide channels by phosphoinositides. Focus on “CNGA3 achromatopsia-associated mutation potentiates the phosphoinositide sensitivity of cone photoreceptor CNG channels by altering intersubunit interactions”

<i>Feedback regulation of cone cyclic nucleotide channels by phosphoinositides</i>. Focus on “CNGA3 achromatopsia-associated mutation potentiates the phosphoinositide sensitivity of cone photoreceptor CNG channels by altering intersubunit interactions”