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Journal of Inorganic Biochemistry Apr 2021A photochemical system utilizing the semisynthetic biomolecular catalyst acetylated cobalt microperoxidase-11 (CoMP11-Ac) along with [Ru(bpy)] as a photosensitizer and...
A photochemical system utilizing the semisynthetic biomolecular catalyst acetylated cobalt microperoxidase-11 (CoMP11-Ac) along with [Ru(bpy)] as a photosensitizer and ascorbic acid as an electron donor is shown to generate hydrogen from water in a visible light-driven reaction. The reductive quenching pathway facilitated by photoexcited [Ru(bpy)] overcomes the high overpotential observed for CoMP11-Ac in electrocatalysis, yielding turnover numbers ranging from 606 to 2390 (2 μM - 0.1 μM CoMP11-Ac). The longevity of CoMP11-Ac in the photochemical system, sustaining catalysis for over 20 h, is in contrast to its previously reported behavior in an electrochemical system where catalysis slows after 15 min. Proton reduction turnover number and rate are highest at a neutral pH, a rare feature among cobalt catalysts in similar photochemical systems, which typically function best under acidic conditions. Incorporating biomolecular components into the design of catalysts for photochemical systems may address the need for hydrogen generation from neutral-pH water sources.
Topics: Catalysis; Cobalt; Coordination Complexes; Hydrogen; Light; Organometallic Compounds; Oxidation-Reduction; Porphyrins
PubMed: 33588276
DOI: 10.1016/j.jinorgbio.2021.111384 -
Proceedings of the National Academy of... Nov 2022The management of biofilm-related infections is a challenge in healthcare, and antimicrobial photodynamic therapy (aPDT) is a powerful tool that has demonstrated a...
The management of biofilm-related infections is a challenge in healthcare, and antimicrobial photodynamic therapy (aPDT) is a powerful tool that has demonstrated a broad-spectrum activity. Nanotechnology has been used to increase the aPDT effectiveness by improving the photosensitizer's delivery properties. NewPS is a simple, versatile, and safe surfactant-free nanoemulsion with a porphyrin salt shell encapsulating a food-grade oil core with promising photodynamic action. This study evaluated the use of NewPS for aPDT against microorganisms in planktonic, biofilm, and in vivo models of infected wounds. First, the potential of NewPS-mediated aPDT to inactivate and suspensions was evaluated. Then, a series of protocols were assessed against biofilms by means of cell viability and confocal microscopy. Finally, the best biofilm protocol was used for the treatment of in a murine-infected wound model. A high NewPS-bacteria cell interaction was achieved since 0.5 nM and 30 J/cm was able to kill suspension. In the biofilm, enhanced efficacy of NewPS-aPDT was achieved when 100 µM of NewPS was applied with longer periods of incubation at the light dose of 60 J/cm. The best single and double-session protocol reduced 5.56 logs and 6.03 logs, respectively, homogeneous NewPS distribution, resulting in a high number of dead cells after aPDT. The in vivo model showed that one aPDT session enabled a reduction of 6 logs and faster tissue healing than the other groups. In conclusion, NewPS-aPDT may be considered a safe and effective anti-biofilm antimicrobial photosensitizer.
Topics: Mice; Animals; Photochemotherapy; Photosensitizing Agents; Porphyrins; Staphylococcus aureus; Biofilms; Anti-Infective Agents; Anti-Bacterial Agents
PubMed: 36346844
DOI: 10.1073/pnas.2216239119 -
Chemistry (Weinheim An Der Bergstrasse,... Apr 2022Metal complexes of multi-porphyrins and multi-corroles are unique systems that display a host of extremely interesting properties. Availability of free meso and β... (Review)
Review
Metal complexes of multi-porphyrins and multi-corroles are unique systems that display a host of extremely interesting properties. Availability of free meso and β positions allow formation of different types of directly linked bis-porphyrins giving rise to intriguing optical and electronic properties. While the fields of metalloporphyrin and corroles monomer have seen exponential growth in the last decades, the chemistry of metal complexes of bis-porphyrins and bis-corroles remain rather underexplored. Therefore, the impact of covalent linkages on the optical, electronic, (spectro)electrochemical, magnetic and electrocatalytic activities of metal complexes of bis-porphyrins and -corroles has been summarized in this review article. This article shows that despite the (still) somewhat difficult synthetic access to these molecules, their extremely exciting properties do make a strong case for pursuing research on these classes of compounds.
Topics: Coordination Complexes; Metalloporphyrins; Porphyrins
PubMed: 35088477
DOI: 10.1002/chem.202104550 -
Inorganic Chemistry Feb 2021Although fluorescent proteins have been utilized for a variety of biological applications, they have several optical limitations, namely weak red and near-infrared...
Although fluorescent proteins have been utilized for a variety of biological applications, they have several optical limitations, namely weak red and near-infrared emission and exceptionally broad (>200 nm) emission profiles. The photophysical properties of fluorescent proteins can be enhanced through the incorporation of novel cofactors with the desired properties into a stable protein scaffold. To this end, a fluorescent phosphorus corrole that is structurally similar to the native heme cofactor is incorporated into two exceptionally stable heme proteins: H-NOX from and heme acquisition system protein A (HasA) from . These yellow-orange emitting protein conjugates are examined by steady-state and time-resolved optical spectroscopy. The HasA conjugate exhibits enhanced fluorescence, whereas emission from the H-NOX conjugate is quenched relative to the free corrole. Despite the low fluorescence quantum yields, these corrole-substituted proteins exhibit more intense fluorescence in a narrower spectral profile than traditional fluorescent proteins that emit in the same spectral window. This study demonstrates that fluorescent corrole complexes are readily incorporated into heme proteins and provides an inroad for the development of novel fluorescent proteins.
Topics: Crystallography, X-Ray; Hemeproteins; Luminescent Proteins; Porphyrins
PubMed: 33513009
DOI: 10.1021/acs.inorgchem.0c03599 -
Journal of the American Chemical Society Jun 2022Light-driven conversion of CO to chemicals provides a sustainable alternative to fossil fuels, but homogeneous systems are typically limited by cross reactivity between...
Light-driven conversion of CO to chemicals provides a sustainable alternative to fossil fuels, but homogeneous systems are typically limited by cross reactivity between different redox half reactions and inefficient charge separation. Herein, we present the bioinspired development of amphiphilic photosensitizer and catalyst pairs that self-assemble in lipid membranes to overcome some of these limitations and enable photocatalytic CO reduction in liposomes using precious metal-free catalysts. Using sodium ascorbate as a sacrificial electron source, a membrane-anchored alkylated cobalt porphyrin demonstrates higher catalytic CO production (1456 vs 312 turnovers) and selectivity (77 vs 11%) compared to its water-soluble nonalkylated counterpart. Time-resolved and steady-state spectroscopy revealed that self-assembly facilitates this performance enhancement by enabling a charge-separation state lifetime increase of up to two orders of magnitude in the dye while allowing for a ninefold faster electron transfer to the catalyst. Spectroelectrochemistry and density functional theory calculations of the alkylated Co porphyrin catalyst support a four-electron-charging mechanism that activates the catalyst prior to catalysis, together with key catalytic intermediates. Our molecular liposome system therefore benefits from membrane immobilization and provides a versatile and efficient platform for photocatalysis.
Topics: Carbon Dioxide; Catalysis; Electrons; Liposomes; Porphyrins
PubMed: 35594410
DOI: 10.1021/jacs.2c01725 -
Oxidative Medicine and Cellular... 2021Mn(III) --alkyl- and -alkoxyalkyl porphyrins (MnPs) were initially developed as superoxide dismutase (SOD) mimics. These compounds were later shown to react with... (Review)
Review
Mn(III) --alkyl- and -alkoxyalkyl porphyrins (MnPs) were initially developed as superoxide dismutase (SOD) mimics. These compounds were later shown to react with numerous reactive species (such as ONOO, HO, HS, CO , ascorbate, and GSH). Moreover, the ability of MnPs to oxidatively modify activities of numerous proteins has emerged as their major mechanism of action both in normal and in cancer cells. Among those proteins are transcription factors (NF-B and Nrf2), mitogen-activated protein kinases, MAPKs, antiapoptotic bcl-2, and endogenous antioxidative defenses. The lead Mn porphyrins, namely, MnTE-2-PyP (BMX-010, AEOL10113), MnTnBuOE-2-PyP (BMX-001), and MnTnHex-2-PyP, were tested in numerous injuries of normal tissue and cellular and animal cancer models. The wealth of the data led to the progression of MnTnBuOE-2-PyP into four Phase II clinical trials on glioma, head and neck cancer, anal cancer, and multiple brain metastases, while MnTE-2-PyP is in Phase II clinical trial on atopic dermatitis and itch.
Topics: Animals; Antineoplastic Agents; Biological Availability; Humans; Hydrogen Peroxide; Manganese; Porphyrins; Signal Transduction
PubMed: 33815656
DOI: 10.1155/2021/6653790 -
Bioconjugate Chemistry Jul 2021Over the past decade, porphyrin derivatives have emerged as invaluable synthetic building blocks and theranostic kits for the delivery of cellular fluorescence imaging...
Over the past decade, porphyrin derivatives have emerged as invaluable synthetic building blocks and theranostic kits for the delivery of cellular fluorescence imaging and photodynamic therapy. Tetraphenylporphyrin (TPP), its metal complexes, and related derivatives have been investigated for their use as dyes in histology and as components of multimodal imaging probes. The photophysical properties of porphyrin-metal complexes featuring radiometals have been a focus of our attention for the realization of fluorescence imaging probes coupled with radioimaging capabilities and therapeutic potential having "true" theranostic promise. We report hereby on the synthesis, radiochemistry, structural investigations, and preliminary and uptake studies on a range of functionalized porphyrin-based derivatives. In pursuit of developing new porphyrin-based probes for multimodality imaging applications, we report new functionalized neutral, polycationic, and polyanionic porphyrins incorporating nitroimidazole and sulfonamide moieties, which were used as targeting groups to improve the notoriously poor pharmacokinetics of porphyrin tags. The resulting functional metalloporphyrin species were stable under serum challenges and the nitroimidazole and sulfonamide derivatives remained fluorescent, allowing confocal studies and visualization of the lysosomal uptake in a gallium(III) sulfonamide derivative. The molecular structures of selected porphyrin derivatives were determined by single crystal X-ray diffraction using synchrotron radiation. We also investigated the nature of the emission/excitation behavior of model functional porphyrins using approaches such as TD DFT in simple solvation models. The conjugation of porphyrins with the [7-13] and [7-14] fragments of bombesin was also achieved, to provide targeting of the gastrin releasing peptide receptor (GRPR). Depending on the metal, probe conjugates of relevance for single photon emission computed tomography (SPECT) or positron emission tomography (PET) probes have been designed and tested hereby, using TPP and related functional free base porphyrins as the bifunctional chelator synthetic scaffold and In[In] or Ga[Ga], respectively, as the central metal ions. Interestingly, for simple porphyrin conjugates good radiochemical incorporation was obtained for both radiometals, but the presence of peptides significantly diminished the radio-incorporation yields. Although the gallium-68 radiochemistry of the bombesin conjugates did not show radiochemical incorporation suitable for studies, likely because the presence of the peptide changed the behavior of the TPP-NH synthon taken alone, the optical imaging assays indicated that the conjugated peptide tags do mediate uptake of the porphyrin units into cells.
Topics: Anions; Cations; Cell Line, Tumor; Density Functional Theory; Humans; Metalloporphyrins; Molecular Structure; Proof of Concept Study; Radioisotopes; Spectrum Analysis
PubMed: 33525868
DOI: 10.1021/acs.bioconjchem.0c00691 -
Retina (Philadelphia, Pa.) Aug 2023We performed a multicenter, retrospective study on patients with bilateral chronic central serous chorioretinopathy (cCSC) who received single-session bilateral...
PURPOSE
We performed a multicenter, retrospective study on patients with bilateral chronic central serous chorioretinopathy (cCSC) who received single-session bilateral reduced-settings photodynamic therapy (ssbPDT) and assessed anatomical (resolution of subretinal fluid [SRF]) and functional (best-corrected visual acuity [BCVA]) outcomes and safety.
METHODS
Patients who underwent ssbPDT between 01/01/2011 and 30/09/2022 were included. The resolution of SRF at first, second, and final follow-up was assessed on optical coherence tomography (OCT), and BCVA measurements were collected at these visits. When fovea-involving ssbPDT was performed, ellipsoid zone (EZ) and external limiting membrane (ELM) integrity was graded before and after treatment.
RESULTS
Fifty-five patients were included in this study. Sixty-two of hundred and eight eyes (56%) showed a complete resolution of SRF at the first follow-up, which increased to 73/110 (66%) at the final follow-up. The mean logMAR BCVA improved by -0.047 ( P = 0.02) over follow-up. EZ integrity increased from 14/21 (67%) to 24/30 (80%) while ELM integrity increased from 22/30 (73%) to 29/30 (97%).
CONCLUSION
Patients with cCSC with bilateral SRF at baseline showed significant anatomical and functional improvements after ssbPDT, both at short-term and long-term follow-up. No relevant adverse events were noted.
Topics: Humans; Central Serous Chorioretinopathy; Photosensitizing Agents; Verteporfin; Retrospective Studies; Porphyrins; Photochemotherapy; Tomography, Optical Coherence; Chronic Disease; Fluorescein Angiography
PubMed: 37307569
DOI: 10.1097/IAE.0000000000003807 -
Magnetic Resonance in Medicine Aug 2019CEST has become a preeminent technology for the rapid detection and grading of tumors, securing its widespread use in both laboratory and clinical research. However,...
PURPOSE
CEST has become a preeminent technology for the rapid detection and grading of tumors, securing its widespread use in both laboratory and clinical research. However, many existing CEST MRI agents exhibit a sensitivity limitation due to small chemical shifts between their exchangeable protons and water. We propose a new group of CEST MRI agents, free-base porphyrins and chlorin, with large exchangeable proton chemical shifts from water for enhanced detection.
METHODS
To test these newly identified CEST agents, we acquired a series of Z-spectra at multiple pH values and saturation field strengths to determine their CEST properties. The data were analyzed using the quantifying exchange using saturation power method to quantify exchange rates. After identifying several promising candidates, a porphyrin solution was injected into tumor-bearing mice, and MR images were acquired to assess detection feasibility in vivo.
RESULTS
Based on the Z-spectra, the inner nitrogen protons in free-base porphyrins and chlorin resonate from -8 to -13.5 ppm from water, far shifted from the majority of endogenous metabolites (0-4 ppm) and Nuclear Overhauser enhancements (-1 to -3.5 ppm) and far removed from the salicylates, imidazoles, and anthranillates (5-12 ppm). The exchange rates are sufficiently slow to intermediate (500-9000 s ) to allow robust detection and were sensitive to substituents on the porphyrin ring.
CONCLUSION
These results highlight the capabilities of free-base porphyrins and chlorin as highly upfield CEST MRI agents and provide a new scaffold that can be integrated into a variety of diagnostic or theranostic agents for biomedical applications.
Topics: A549 Cells; Animals; Contrast Media; Humans; Magnetic Resonance Imaging; Mice; Mice, Inbred BALB C; Molecular Imaging; Neoplasms, Experimental; Phantoms, Imaging; Porphyrins; Protons
PubMed: 30968442
DOI: 10.1002/mrm.27753 -
Scientific Reports Sep 2023Oxygenation is a crucial indicator of tissue viability and function. Oxygen tension ([Formula: see text]), i.e. the amount of molecular oxygen present in the tissue is a...
Oxygenation is a crucial indicator of tissue viability and function. Oxygen tension ([Formula: see text]), i.e. the amount of molecular oxygen present in the tissue is a direct result of supply (perfusion) and consumption. Thus, measurement of [Formula: see text] is an effective method to monitor tissue viability. However, tissue oximetry sensors commonly used in clinical practice instead rely on measuring oxygen saturation ([Formula: see text]), largely due to the lack of reliable, affordable [Formula: see text] sensing solutions. To address this issue we present a proof-of-concept design and validation of a low-cost, lifetime-based oxygen sensing fiber. The sensor consists of readily-available off-the shelf components such as a microcontroller, a light-emitting diode (LED), an avalanche photodiode (APD), a temperature sensor, as well as a bright in-house developed porphyrin molecule. The device was calibrated using a benchtop setup and evaluated in three in vivo animal models. Our findings show that the new device design in combination with the bright porphyrin has the potential to be a useful and accurate tool for measuring [Formula: see text] in tissue, while also highlighting some of the limitations and challenges of oxygen measurements in this context.
Topics: Animals; Blood Gas Analysis; Fiber Optic Technology; Oximetry; Oxygen; Porphyrins
PubMed: 37679415
DOI: 10.1038/s41598-023-41917-5