Porphyrin Scaffold Research Articles

Combining experiment and energy landscapes to explore anaerobic heme breakdown in multifunctional hemoproteins.

To survive, many pathogens extract heme from their host organism and break down the porphyrin scaffold to sequester the Fe2+ ion via a heme oxygenase. Recent studies have revealed that certain pathogens can anaerobically degrade heme. Our own research has shown that one such pathway proceeds via NADH-dependent heme degradation, which has been identified in a family of hemoproteins from a range of bacteria. HemS, from Yersinia enterocolitica, is the main focus of this work, along with HmuS (Yersinia pestis), ChuS (Escherichia coli) and ShuS (Shigella dysenteriae). We combine experiments, Energy Landscape Theory, and a bioinformatic investigation to place these homologues within a wider phylogenetic context. A subset of these hemoproteins are known to bind certain DNA promoter regions, suggesting not only that they can catalytically degrade heme, but that they are also involved in transcriptional modulation responding to heme flux. Many of the bacterial species responsible for these hemoproteins (including those that produce HemS, ChuS and ShuS) are known to specifically target oxygen-depleted regions of the gastrointestinal tract. A deeper understanding of anaerobic heme breakdown processes exploited by these pathogens could therefore prove useful in the development of future strategies for disease prevention.

C60-based Multivalent Glycoporphyrins Inhibit SARS-CoV-2 Specific Interaction with the DC-SIGN Transmembrane Receptor.

Since WHO has declared the COVID-19 outbreak a global pandemic, nearly seven million deaths have been reported. This efficient spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is facilitated by the ability of the spike glycoprotein to bind multiple cell membrane receptors. Although ACE2 is identified as the main receptor for SARS-CoV-2, other receptors could play a role in viral entry. Among others, C-type lectins such as DC-SIGN are identified as efficient trans-receptor for SARS-CoV-2 infection, so the use of glycomimetics to inhibit the infection through the DC-SIGN blockade is an encouraging approach. In this regard, multivalent nanostructures based on glycosylated [60]fullerenes linked to a central porphyrin scaffold have been designed and tested against DC-SIGN-mediated SARS-CoV-2 infection. First results show an outstanding inhibition of the trans-infection up to 90%. In addition, a deeper understanding of nanostructure-receptor binding is achieved through microscopy techniques, high-resolution NMR experiments, Quartz Crystal Microbalance experiments, and molecular dynamic simulations.

Chiral Iron Porphyrins Catalyze Enantioselective Intramolecular C(sp3)−H Bond Amination Upon Visible‐Light Irradiation

AbstractIron‐catalyzed asymmetric amination of C(sp3)−H bonds is appealing for synthetic applications due to the biocompatibility and high earth abundance of iron, but examples of such reactions are sparse. Herein we describe chiral iron complexes of meso‐ and β‐substituted‐porphyrins that can catalyze asymmetric intramolecular C(sp3)−H amination of aryl and arylsulfonyl azides to afford chiral indolines (29 examples) and benzofused cyclic sulfonamides (17 examples), respectively, with up to 93 % ee (yield: up to 99 %) using 410 nm light under mild conditions. Mechanistic studies, including DFT calculations, for the reactions of arylsulfonyl azides reveal that the Fe(NSO2Ar) intermediate generated in situ under photochemical conditions reacts with the C(sp3)−H bond through a stepwise hydrogen atom transfer/radical rebound mechanism, with enantioselectivity arising from cooperative noncovalent interactions between the Fe(NSO2Ar) unit and the peripheral substituents of the chiral porphyrin scaffold.

Chiral Iron Porphyrins Catalyze Enantioselective Intramolecular C(sp3 )-H Bond Amination Upon Visible-Light Irradiation.

Iron-catalyzed asymmetric amination of C(sp3 )-H bonds is appealing for synthetic applications due to the biocompatibility and high earth abundance of iron, but examples of such reactions are sparse. Herein we describe chiral iron complexes of meso- and β-substituted-porphyrins that can catalyze asymmetric intramolecular C(sp3 )-H amination of aryl and arylsulfonyl azides to afford chiral indolines (29 examples) and benzofused cyclic sulfonamides (17 examples), respectively, with up to 93 % ee (yield: up to 99 %) using 410 nm light under mild conditions. Mechanistic studies, including DFT calculations, for the reactions of arylsulfonyl azides reveal that the Fe(NSO2 Ar) intermediate generated in situ under photochemical conditions reacts with the C(sp3 )-H bond through a stepwise hydrogen atom transfer/radical rebound mechanism, with enantioselectivity arising from cooperative noncovalent interactions between the Fe(NSO2 Ar) unit and the peripheral substituents of the chiral porphyrin scaffold.

Porphyrin(2.1.2.1) rhenium(I) complexes: Synthesis, structures, properties, and dipyrrin act as bipyridyl-like ligand

Two new rhenium(I) porphyriniod complexes (H2PY: 3,3-rhenium(I) tricarbonyl chloride-(31 E,32 Z,71 E,72 Z)-4,8-bis(perfluorophenyl)-11 H,32 H,72 H-51 λ2 ,71 λ4 -1,5(2,5),3,7(5,2)-tetrapyrrola-2,6(1,2)-dibenzenacyclooctaphane, and H2PZ: 3,3-rhenium(I) tricarbonyl acetate-(31 E,32 Z,71 E,72 Z)-4,8-bis(perfluorophenyl)-11 H,32 H,72 H-51 λ2 ,71 λ4 -1,5(2,5),3,7(5,2)-tetrapyrrola-2,6(1,2)-dibenzenacyclooctaphane) containing two different Re(I)−N π-bonding networks were prepared from the saddle-shaped porphyrin(2.1.2.1) bearing pentafluorophenyl substituents at the two meso-positions (H2Por: 31 E,32 Z,71 E,72 Z)-4,8-bis(perfluorophenyl)-11 H,32 H,51 H,72 H-1,5(2,5),3,7(5,2)-tetrapyrrola-2,6(1,2)-dibenzenacyclooctaphane). Despite the tetrapyrrolic nature of the porphyrin(2.1.2.1) scaffold, this is the first case of a pyrrole-based macrocycle which acts as a bipyridyl-like complexing ligand in the formation of an octahedral Re(I) complex. X-ray analysis and 1H NMR studies show that both Re(I) complexes (H2PY and H2PZ) consist of one octahedral Re(I) ion π-bonded to a dipyrrin unit and one protonated dipyrrin moiety linked together through o-phenylene bridges. This bonding behavior is compared to related metal complexes of porphyrin(2.1.2.1) macrocycles as well as other Re(I) porphyrins and demonstrates that the distorted conformation and, by virtue, the electronics of H2Por serve as a novel platform for examining structure property relationships which differ than those of other related planar porphyrin macrocycles.

Porphyrin as a versatile visible-light-activatable organic/metal hybrid photoremovable protecting group

Photoremovable protecting groups (PPGs) represent one of the main contemporary implementations of photochemistry in diverse fields of research and practical applications. For the past half century, organic and metal-complex PPGs were considered mutually exclusive classes, each of which provided unique sets of physical and chemical properties thanks to their distinctive structures. Here, we introduce the meso-methylporphyrin group as a prototype hybrid-class PPG that unites traditionally exclusive elements of organic and metal-complex PPGs within a single structure. We show that the porphyrin scaffold allows extensive modularity by functional separation of the metal-binding chromophore and up to four sites of leaving group release. The insertion of metal ions can be used to tune their spectroscopic, photochemical, and biological properties. We provide a detailed description of the photoreaction mechanism studied by steady-state and transient absorption spectroscopies and quantum-chemical calculations. Our approach applied herein could facilitate access to a hitherto untapped chemical space of potential PPG scaffolds.

Porphyrin in Prebiotic Catalysis: Ascertaining a Route for the Emergence of Early Metalloporphyrins.

Metal ions are known to catalyze certain prebiotic reactions. However, the transition from metal ions to extant metalloenzymes remains unclear. Porphyrins are found ubiquitously in the catalytic core of many ancient metalloenzymes. In this study, we evaluated the influence of porphyrin-based organic scaffold, on the catalysis, emergence and putative molecular evolution of prebiotic metalloporphyrins. We studied the effect of porphyrins on the transition metal ion-mediated oxidation of hydroquinone (HQ). We report a change in the catalytic activity of the metal ions in the presence of porphyrin. This was observed to be facilitated by the coordination between metal ions and porphyrins or by the formation of non-coordinated complexes. The metal-porphyrin complexes also oxidized NADH, underscoring its versatility at oxidizing more than one substrate. Our study highlights the selective advantage that some of the metal ions would have had in the presence of porphyrin, underscoring their role in shaping the evolution of protometalloenzymes.

The Red Color of Life Transformed - Synthetic Advances and Emerging Applications of Protoporphyrin IX in Chemical Biology.

Protoporphyrin IX (PPIX) is the porphyrin scaffold of heme b, a ubiquitous prosthetic group of proteins responsible for oxygen binding (hemoglobin, myoglobin), electron transfer (cytochrome c) and catalysis (cytochrome P450, catalases, peroxidases). PPIX and its metallated derivatives frequently find application as therapeutic agents, imaging tools, catalysts, sensors and in light harvesting. The vast toolkit of accessible porphyrin functionalization reactions enables easy synthetic modification of PPIX to meet the requirements for its multiple uses. In the past few years, particular interest has arisen in exploiting the interaction of PPIX and its synthetic derivatives with biomolecules such as DNA and heme‐binding proteins to evolve molecular devices with new functions as well as to uncover potential therapeutic toeholds. This review strives to shine a light on the most recent developments in the synthetic chemistry of PPIX and its uses in selected fields of chemical biology.

Octapodal Corannulene Porphyrin-Based Assemblies: Allosteric Behavior in Fullerene Hosting.

An octapodal corannulene-based supramolecular system has been prepared by introducing eight corannulene moieties in a porphyrin scaffold. Despite the potential of this double picket fence porphyrin for double-tweezer behavior, NMR titrations show exclusive formation of 1:1 adducts. The system exhibits very strong affinity for C60 and C70 (K1 = (2.71 ± 0.08) × 104 and (2.13 ± 0.1) × 105 M-1, respectively), presenting selectivity for the latter. Density functional theory (DFT) calculations indicate that, in addition to the four corannulene units, the relatively flexible porphyrin tether actively participates in the recognition process, resulting in a strong synergistic effect. This leads to a very strong interaction with C60, which in turn also induces a large structural change on the other face (second potential binding site), leading to a negative allosteric effect. We also introduced Zn2+ in the porphyrin core in an attempt to modulate its flexibility. The resulting metalloporphyrin also displayed single-tweezer behavior, albeit with slightly smaller binding constants for C60 and C70, suggesting that the effect of the coordination of fullerene to one face of our supramolecular platform was still transmitted to the other face, leading to the deactivation of the second potential binding site.

Synthesis and Characterization of Novel Quinolyl Porphyrins as Receptors. Study of their Association with Halophenols and 4‐Nitrophenol as a Reference

In this work, new receptors built on the porphyrin scaffold were synthesized for halophenols recognition. A quinolyl group was introduced on the porphyrin's periphery as binding site, to form two series of molecules based on two distinct porphyrin frames and which were obtained in free base and zinc forms. The binding between these porphyrin‐based receptors and halophenols (2,3,4,6‐tetrachlorophenol, 2,4,6‐trichlorophenol or 2,4,6‐tribromophenol) was studied. As established by 1H NMR spectroscopy, the binding constants are in the range of two‐digit numbers, which value is correlated with the porphyrin structure (substitutive pattern, form of the free base or ZnII complex) and the pKa of the respective phenol. These data, supplemented by a X‐ray structure of one adduct complex, indicate a single interaction between the phenolic proton and the nitrogen of the quinolyl group. The binding with p‐nitrophenol was tested for comparison. The association constant increases at a scale of one order of magnitude. This net stabilization of the adduct complex in this case is explained by additional hydrogen bonds implying the nitro function, as also witnessed by X‐ray diffractometry.

An anticancer gold(III)-activated porphyrin scaffold that covalently modifies protein cysteine thiols

Cysteine thiols of many cancer-associated proteins are attractive targets of anticancer agents. Herein, we unequivocally demonstrate a distinct thiol-targeting property of gold(III) mesoporphyrin IX dimethyl ester (AuMesoIX) and its anticancer activities. While the binding of cysteine thiols with metal complexes usually occurs via M-S bond formation, AuMesoIX is unique in that the meso-carbon atom of the porphyrin ring is activated by the gold(III) ion to undergo nucleophilic aromatic substitution with thiols. AuMesoIX was shown to modify reactive cysteine residues and inhibit the activities of anticancer protein targets including thioredoxin, peroxiredoxin, and deubiquitinases. Treatment of cancer cells with AuMesoIX resulted in the formation of gold-bound sulfur-rich protein aggregates, oxidative stress-mediated cytotoxicity, and accumulation of ubiquitinated proteins. Importantly, AuMesoIX exhibited effective antitumor activity in mice. Our study has uncovered a gold(III)-induced ligand scaffold reactivity for thiol targeting that can be exploited for anticancer applications.

Synthesis and Characterization of Novel Fluoro-glycosylated Porphyrins that can be Utilized as Theranostic Agents.

Invited for this month's cover picture is the group of Professor Peter Nilsson at the Department of Physics, Chemistry and Biology at Linköping University (Sweden). The cover picture shows a fluoro‐glycoporphyrin that selectively targets cancer cells. The selectivity towards cancer cells are afforded due to proper functionalization of the porphyrin scaffold with specific carbohydrates, and the cancer cells can be visualized because of the intrinsic fluorescence from the porphyrin. The molecule also exhibits properties for photodynamic therapy and the incorporation of fluorine, in the form of 2‐fluoro‐2‐deoxy glucose (FDG), offers the possibility to apply these compounds as 18F positron emission tomography (PET) tracers. Thus, fluoro‐glycoporphyrins display multimodal properties and can be employed as theranostic agents targeting cancer cells. Read the full text of their Full Paper at https://doi.org/10.1002/open.201800020.

A Self-Assembled Cofacial Cobalt Porphyrin Prism for Oxygen Reduction Catalysis.

Herein we report the first study of the oxygen reduction reaction (ORR) catalyzed by a cofacial porphyrin scaffold accessed in high yield (overall 53%) using coordination-driven self-assembly with no chromatographic purification steps. The ORR activity was investigated using chemical and electrochemical techniques on monomeric cobalt(II) tetra(meso-4-pyridyl)porphyrinate (CoTPyP) and its cofacial analogue [Ru8(η6-iPrC6H4Me)8(dhbq)4(CoTPyP)2][OTf]8 (Co Prism) (dhbq = 2,5-dihydroxy-1,4-benzoquinato, OTf = triflate) as homogeneous oxygen reduction catalysts. Co Prism is obtained in one self-assembly step that organizes six total building blocks, two CoTPyP units and four arene-Ru clips, into a cofacial motif previously demonstrated with free-base, Zn(II), and Ni(II) porphyrins. Turnover frequencies (TOFs) from chemical reduction (66 vs 6 h-1) and rate constants of overall homogeneous catalysis (kobs) determined from rotating ring-disk experiments (1.1 vs 0.05 h-1) establish a cofacial enhancement upon comparison of the activities of Co Prism and CoTPyP, respectively. Cyclic voltammetry was used to initially probe the electrochemical catalytic behavior. Rotating ring-disk electrode studies were completed to probe the Faradaic efficiency and obtain an estimate of the rate constant associated with the ORR.

Extensive methodology screening of meso-tetrakys-(furan-2-yl)-porphyrin microwave-assisted synthesis

meso-Tetrakys-(furan-2-yl)-porphyrin has been prepared by a one step, microwave assisted, fast procedure. The Diels–Alder reaction is proposed to further decorate the porphyrin scaffold.

Diamondoid framework solid with Sn(OCH₃)₂-tetrapyridylporphyrin linkers, CuI nodes and [CuICl₂]⁻ counter-ions.

We report on the synthesis of a new metal-organic framework (MOF) composed of Sn(OCH3)2-tetrakis(pyridin-4-yl)porphyrin linkers, Cu(+) connecting nodes and [CuCl2](-) counter-ions, namely poly[[bis(methanolato-κO)[μ5-5,10,15,20-tetrakis(pyridin-4-yl)porphyrin-κ(8)1κN(5):1'κN(10):1''κN(15):1'''κN(20):2κ(4)N(21),N(22),N(23),N(24)]copper(I)tin(II)] dichloridocuprate(I)], [CuSn(C40H24N8)(CH3O)2][CuCl2]. Its crystal structure consists of a single-framework coordination polymer of the organic ligand and the Cu(I) ions. The latter are characterized by a tetrahedral coordination geometry [with CN (coordination number) = 4], linking to the pyridyl N-atom sites of four different ligands and imparting to the positively charged polymeric assembly a diamondoid PtS-type topology. Correspondingly, every porphyrin unit is coordinated to four different Cu(I) connectors. The [CuCl2](-) anions occupy the intra-lattice voids, along with disordered molecules of the water crystallization solvent. The asymmetric unit of this structure consists of two halves of the porphyrin scaffold, located on centres of crystallographic inversion, and the Cu(+) and [CuCl2](-) ions. This report provides unique structural evidence for the formation of tetrapyridylporphyrin-based three-dimensional MOFs with a diamondoid architecture that have been observed earlier only on rare occasions.

Host-guest interactions derived multilayer perylene diimide thin film constructed on a scaffolding porphyrin monolayer.

The development of methods to grow well-ordered chromophore thin films on solid substrates is of importance because such surface-associated arrays have potential applications in the generation of functional electronic and optical materials and devices. In this article, we demonstrate a straightforward layer-by-layer (LBL) supramolecular deposition strategy to prepare numerous layers (up to 19) of functionalized perylene diimide (PDI) chromophores built upon a covalent scaffolding multivalent porphyrin monolayer. Our thin film formation strategy employs water as the immersion solvent and exploits the β-cyclodextrin-adamantane host-guest couple in addition to PDI based aromatic stacking. Within the resultant film the porphyrin scaffold is oriented close to parallel to the glass substrate while the PDI chromophores are aligned closer to the surface normal. Together, the porphyrin monolayer and the multi-PDI layers exhibit a large absorption bandwidth in the visible spectrum. Importantly, because a self-assembly strategy was utilized, when a single monolayer of PDI is deposited on the porphyrin scaffolding layer, this PDI monolayer can be readily disassembled by washing with DMF leading to the regeneration of the porphyrin monolayer. The PDI thin film can subsequently be regrown from the regenerated porphyrin surface. The reported LBL strategy will be of broad interest for researchers developing well-organized chromophoric films and materials due to its simplicity as well as the added advantage of being performed in sustainable and cost-effective aqueous media.

Axially bonded pentads constructed on the Sn(iv) porphyrin scaffold

Three covalently linked dyads such as porphyrin-ferrocene, porphyrin-BODIPY and porphyrin-sapphyrin containing one hydroxyphenyl group at the meso-position of porphyrin were synthesized by coupling the trans-functionalized porphyrin building block, 5-(4-hydroxyphenyl)-10-(4-iodophenyl)-15,20-diphenyl porphyrin, with the ethynyl functionalized redox/chromophore building block under mild Pd(0) coupling conditions. The dyads were then reacted with SnTTP(OH)2 in benzene in a 2 : 1 ratio at reflux temperature for 12 hours followed by simple alumina column chromatographic purification which afforded three pentads containing three different types of redox/chromophore components in 62-80% yields. The pentads are very stable and freely soluble in all common organic solvents. The pentads formation were confirmed by MALDI-TOF mass spectrometry and 1D and 2D NMR studies. Absorption and electrochemical studies suggested that the three components in pentads retain their independent characteristic features without significant alterations in their properties thus acting like supramolecular assemblies. The steady state fluorescence studies indicated a possibility of energy/electron transfer among the three types of components in pentads.

N-Heterocyclic carbene bonding to cobalt porphyrin complexes

N-Heterocyclic carbene (NHC) coordination to a cobalt(III) center embedded in a porphyrin scaffold has been accomplished by decarboxylation from N,N′-dimethylimidazolium-2-carboxylate in the presence of Co(TPP)Cl (TPP=5,10,15,20-tetraphenylporphyrin). The distal chloride ligand in the resulting complex Co(NHC)(TPP)Cl was successfully substituted with imidazoles and alcohols. Single crystal X-ray diffraction of the latter complexes Co(NHC)(TPP)(ROH) (R=Me, Et) revealed a pronounced ruffling of the porphyrin macrocycle due to the two ortho methyl groups in the carbene ligand and because of the relatively short distance between the cobalt center and the carbene ligand. Spectroscopic investigations support a substantial porphyrin dearomatization upon NHC bonding.

Supramolecular Crystal Chemistry of Tetra(3-pyridyl)porphyrin. 2. Two- and Three-Dimensional Coordination Networks with Cobalt and Cadmium Ions

New hybrid coordination polymers have been self-assembled with the conformationally versatile tetra(3-pyridyl)porphyrin (T3PyP) scaffold. Hydrothermal reactions with cobalt ions resulted in metalation of the porphyrin core and self-coordination of the CoT3PyP units through their endocyclic metal centers into two-dimensional (2D) polymeric arrays. These crystallized into interdigitated, either solvent-free or N,N-dimethylformamide-solvated, structures. Interaction of the T3PyP with cadmium ions yielded three-dimensional (3D) framework solids tessellated by exocyclic CdCl2 connectors to the peripheral pyridyl sites of neighboring units of either the freebase porphyrin or its CdT3PyP analogue. The complementary tetradenate nature of the porphyrin linkers and CdCl2 nodes resulted in pseudodiamondoid polymerization schemes.

Appending zinc tetraphenylporphyrin with an amine receptor at β-pyrrolic carbon for designing a selective histamine chemosensor

Adopting the rarely used β-functionalisation strategy in porphyrin-based sensor design, an amine receptive site is appended onto the zinc(II) porphyrin molecular framework affording a ditopic chemosensor 4. The assembled chemosensor interacts selectively with histamine in toluene via a ‘two-site’ binding mode. Association constant of the complex evaluated from the respective UV–vis spectra is found to be (2.32 ± 0.57) × 106, which is approximately 4-fold greater than those complexes derived from 4 and nicotine/histidine. On the basis of a combined spectroscopic method and molecular modelling, the binding model of the porphyrin host and biogenic guest molecules is established. Our results clearly demonstrate the viability of the design and development of the porphyrin-based chemosensor by appending a receptor at the β-pyrrolic carbon of the porphyrin scaffold.