The Excited-State N-H Tautomerization Rate in Free-Base Corroles.

Corrole is a tetrapyrrolic dye with a structure that resembles porphyrin, apart from a single missing carbon. The absence of this carbon results in the re-arrangement of the double bonds within the macrocycle, and the presence of three pyrrolic protons in the central cavity in its free-base form. These protons lead to the existence of two distinct tautomeric structures that exist in a dynamic equilibrium. Although the ground-state energies of the tautomers are similar, the excited states show a significant difference in energy which unbalances the equilibrium between the tautomers and results in rapid excited-state tautomerization, favouring one tautomeric species over the other. Although the excited-state tautomerization process has been known for a long time, very few studies have been performed on it, leaving many key aspects of the process poorly understood. Herein we show how ultrafast photoluminescence can be used to experimentally determine the rates of excited-state tautomerization and activation energies of three free-base corrole derivatives thus allowing us to completely describe the excited-state dynamics of the unusual excited state of free-base corrole and opening the door to the development of new materials that can exploit its unique characteristics.

Hallmarks of anticancer and antimicrobial activities of corroles.

Corroles provide a remarkable opportunity for the development of cancer theranostic agents among other porphyrinoids. While most transition metal corrole complexes are only therapeutic, post-transition metallocorroles also find their applications in bioimaging. Moreover, corroles exhibit excellent photo-physicochemical properties, which can be harnessed for antitumor and antimicrobial interventions. Nevertheless, these intriguing, yet distinct properties of corroles, have not attained sufficient momentum in cancer research. The current review provides a comprehensive summary of various cancer-relevant features of corroles ranging from their structural and photophysical properties, chelation, protein/corrole interactions, to DNA intercalation. Another aspect of the paper deals with the studies of corroles conducted in vitro and in vivo with an emphasis on medical imaging (optical and magnetic resonance), photo/sonodynamic therapies, and photodynamic inactivation. Special attention is also given to a most recent finding that shows the development of pH-responsive phosphorus corrole as a potent antitumor drug for organelle selective antitumor cytotoxicity in preclinical studies. Another biomedical application of corroles is also highlighted, signifying the application of water-soluble and completely lipophilic corroles in the photodynamic inactivation of microorganisms. We strongly believe that future studies will offer a greater possibility of utilizing advanced corroles for selective tumor targeting and antitumor cytotoxicity. In the line with future developments, an ideal pipeline is envisioned on grounds of cancer targeting nanoparticle systems upon decoration with tumor-specific ligands. Hence, we envision that a bright future lies ahead of corrole anticancer research and therapeutics.

Synthesis of Pyrrole-Sharing Fused Porphyrinoid Hybrids by Post-fabrication of Ni(II) Porphyrins.

Pyrrole-sharing fused hybrids of NiII porphyrin with PdII N-confused(NC)-corrole and PdII NC-oxaporphyrin were synthesized by post-fabrication of NiII porphyrins. Specifically this consists of Friedel-Crafts type aromatic substitution reaction of meso-free NiII porphyrin with α,α'-dibromotripyrrin and Pd(OAc)2 assisted cyclization, and final heating to induce a Pd-C bond formation. NiII porphyrins fused with PdII NC-corrole and with PdII NC-oxaporphyrins show coplanar structures with a shared pyrrole unit. In these hybrids, the PdII NC-oxaporphyrin is aromatic and the PdII NC-corrole is moderately antiaromatic and these local electronic properties interact to influence the whole network.

Palladium Complexes of N-Methylcorroles.

Alkylation of one of the inner-core nitrogen atoms is one possible approach to obtain dianionic corrole ligands, suitable for the coordination of divalent metal ions, such as PdII . Inner-core N-methylation can be obtained by treating the corrole with CH3 I, but the reaction conditions should be optimized to limit the formation of the dimethylated derivative. Two regioisomers, the N-21 and the N-22 methyl derivatives are obtained from the reaction, with the first product achieved in a higher amount. Structural characterization of the reaction products evidenced the distortion induced by the introduction of the methyl groups; the N-methylcorroles are chiral compounds, and the enantiomers were separated by chromatography, with their absolute configuration assigned by ECD computation. Palladium insertion was achieved in the case of monosubstituted corroles, but not with the dimethylated macrocycle; X-ray characterization of the complexes showed the distortion of the macrocycles. The Pd complexes do not show luminescence emission, but are able to produce singlet oxygen upon irradiation. The PdII complexes were also inserted in human serum albumin (HSA) and dispersed in water; in this case, the protein protects the corroles from photobleaching, and a switch from the type II to the type I mechanism in reactive oxygen species (ROS) production is observed.

One Carbon Ring Expansion of Bipyrrole to Bipyridine Enables Access to a π-Extended, Non-innocent, Corrole-like Ligand.

A π-extended, diaza-triphenylene embedded, mono-anionic corrole analogue and its NiII complex were synthesized from a diaza-triphenylene precursor, which was obtained from a double one-carbon insertion into a naphthobipyrrole diester. Following conversion to the corresponding activated diol and acid-catalyzed condensation with pyrrole, subsequent reaction with pentafluorobenzaldehyde afforded mono-anionic, π-extended bipyricorrole-like macrocycle. Attempted NiII insertion with Ni(OAc)2 ⋅ 4H2 O resulted an ESR active, NiII bipyricorrole radical complex, which was converted to a stable cationic NiII complex upon treatment with [(Et3 O)+ (SbCl6 )- ]. Both complexes were characterized by 1 H and 13 C NMR, UV/Vis spectroscopy and single crystal X-ray diffraction analysis. The NiII bipyricorrole radical complex is converted to a cationic NiII complex by single-electron reduction using cobaltocene. Both the cationic NiII complex and the radical NiII complex exhibited ligand-centered redox behavior, whereas the NiII remains in the +2 oxidation state.

Deciphering Electronic and Structural Effects in Copper Corrole/Graphene Hybrids.

Non-covalent hybrid materials based on graphene and A3 -type copper corrole complexes were computationally investigated. The corroles complexes contain strong electron-withdrawing fluorinated substituents at the meso positions. Our results show that the non-innocent character of corrole moiety modulates the structural, electronic, and magnetic properties once the hybrid systems are held. The graphene-corrole hybrids displayed outstanding stability via the interplay of dispersion and electrostatic driving forces, while graphene act as an electron reservoir. The hybrid structures exposed an intriguing magneto-chemical performance, compared to the isolated counterparts, that evidenced how structural and electronic effects contributed to the magnetic response for both ferromagnetic and antiferromagnetic cases. Directional spin polarization and spin transfer from the corrole to the graphene surface participate in the amplification. Finally, there are relations between the spin transfer, the magnetic response, and the copper distorted ligand field, offering exciting hints about modulating the magnetic response. Therefore, this work shows that copper corroles emerged as versatile building blocks for graphene hybrid materials, especially in applications requiring a magnetic response.

Effects of Substituents on the Photophysical/Photobiological Properties of Mono-Substituted Corroles.

The trans-A2B-corrole series was prepared starting with 5-(pentafluorophenyl)dipyrromethene, which was then reacted with respective aryl-substituted aldehyde by Gryko synthesis. It was further characterized by HRMS and electrochemical methods. In addition, we investigated experimental photophysical properties (absorption, emission by steady-state and time-resolved fluorescence) in several solvents and TDDFT calculations, aggregation, photostability and reactive oxygen species generation (ROS), which are relevant when selecting photosensitizers used in photodynamic therapy and many other photo-applications. In addition, we also evaluated the biomolecule-binding properties with CT-DNA and HSA by spectroscopy, viscometry and molecular docking calculations assays.

A Bifunctional Electrocatalyst for OER and ORR based on a Cobalt(II) Triazole Pyridine Bis-[Cobalt(III) Corrole] Complex.

As alternative energy sources are essential to reach a climate-neutral economy, hydrogen peroxide (H2 O2 ) as futuristic energy carrier gains enormous awareness. However, seeking for stable and electrochemically selective H2 O2 ORR electrocatalyst is yet a challenge, making the design of-ideally-bifunctional catalysts extremely important and outmost of interest. In this study, we explore the application of a trimetallic cobalt(II) triazole pyridine bis-[cobalt(III) corrole] complex CoII TP[CoIII C]2 3 in OER and ORR catalysis due to its remarkable physicochemical properties, fast charge transfer kinetics, electrochemical reversibility, and durability. With nearly 100 % selective catalytic activity towards the two-electron transfer generated H2 O2 , an ORR onset potential of 0.8 V vs RHE and a cycling stability of 50 000 cycles are detected. Similarly, promising results are obtained when applied in OER catalysis. A relatively low overpotential at 10 mA cm-2 of 412 mV, Faraday efficiency 98 % for oxygen, an outstanding Tafel slope of 64 mV dec-1 combined with superior stability.

Controlling Electronic Events Through Rational Structural Design in Subphthalocyanine-Corrole Dyads: Synthesis, Characterization, and Photophysical Properties.

Porphyrinoids are considered perfect candidates for their incorporation into electron donor-acceptor (D-A) arrays due to their remarkable optoelectronic properties and low reorganization energies. For the first time, a series of subphthalocyanine (SubPc) and corrole (Cor) were covalently connected through a short-range linkage. SubPc axial substitution strategies were employed, which allowed the synthesis of the target molecules in decent yields. In this context, a qualitative synthetic approach was performed to reverse the expected direction of the different electronic events. Consequently, in-depth absorption, fluorescence, and electrochemical assays enabled the study of electronic and photophysical properties. Charge separation was observed in cases of electron-donating Cors, whereas a quantitative energy transfer from the Cor to the SubPc was detected in the case of electron accepting Cors.

Metal Complexes of Singly, Doubly and Triply Linked Porphyrins and Corroles: An Insight into the Physicochemical Properties.

Metal complexes of multi-porphyrins and multi-corroles are unique systems that display a host of extremely interesting properties. Availability of free meso and ß 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.

Fluorine Atoms on C6H5-Corrole Affect the Interaction with Mpro and PLpro Proteases of SARS-CoV-2: Molecular Docking and 2D-QSAR Approaches.

The chymotrypsin-like cysteine protease (3CLpro, also known as main protease-Mpro) and papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been used as the main targets for screening potential synthetic inhibitors for posterior in vitro evaluation of the most promising compounds. In this sense, the present work reports for the first time the evaluation of the interaction between Mpro/PLpro with a series of 17 porphyrin analogues-corrole (C1), meso-aryl-corrole (C2), and 15 fluorinated-meso-aryl-corrole derivatives (C3-C17) via molecular docking calculations. The impact of fluorine atoms on meso-aryl-corrole structure was also evaluated in terms of binding affinity and physical-chemical properties by two-dimensional quantitative structure-activity relationship (2D-QSAR). The presence of phenyl moieties increased the binding capacity of corrole for both proteases and depending on the position of fluorine atoms might impact positively or negatively the binding capacity. For Mpro the para-fluorine atoms might decrease drastically the binding capacity, while for PLpro there was a certain increase in the binding affinity of fluorinated-corroles with the increase of fluorine atoms into meso-aryl-corrole structure mainly from tri-fluorinated insertions. The 2D-QSAR models indicated two separated regions of higher and lower affinity for Mpro:C1-C17 based on dual electronic parameters (σI and σR), as well as one model was obtained with a correlation between the docking score value of Mpro:C2-C17 and the corresponding 13C nuclear magnetic resonance (NMR) chemical shifts of the sp2 carbon atoms (δC-1 and δC-2) of C2-C17. Overall, the fluorinated-meso-aryl-corrole derivatives showed favorable in silico parameters as potential synthetic compounds for future in vitro assays on the inhibition of SARS-CoV-2 replication.

Metal-Corrole-Based Porous Organic Polymers for Electrocatalytic Oxygen Reduction and Evolution Reactions.

Integrating molecular catalysts into designed frameworks often enables improved catalysis. Compared with porphyrin-based frameworks, metal-corrole-based frameworks have been rarely developed, although monomeric metal corroles are usually more efficient than porphyrin counterparts for the electrocatalytic oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). We herein report on metal-corrole-based porous organic polymers (POPs) as ORR and OER electrocatalysts. M-POPs (M=Mn, Fe, Co, Cu) were synthesized by coupling metal 10-phenyl-5,15-(4-iodophenyl)corrole with tetrakis(4-ethynylphenyl)methane. Compared with metal corrole monomers, M-POPs displayed significantly enhanced catalytic activity and stability. Co-POP outperformed other M-POPs by achieving four-electron ORR with a half-wave potential of 0.87 V vs. RHE and reaching 10 mA cm-2 OER current density at 340 mV overpotential. This work is unparalleled to develop and explore metal-corrole-based POPs as electrocatalysts.

Synergistic Dual-Atom Molecular Catalyst Derived from Low-Temperature Pyrolyzed Heterobimetallic Macrocycle-N4 Corrole Complex for Oxygen Reduction.

A heterobimetallic corrole complex, comprising oxygen reduction reaction (ORR) active non-precious metals Co and Fe with a corrole-N4 center (PhFCC), is successfully synthesized and used to prepare a dual-atom molecular catalyst (DAMC) through subsequent low-temperature pyrolysis. This low-temperature pyrolyzed electrocatalyst exhibited impressive ORR performance, with onset potentials of 0.86 and 0.94 V, and half-wave potentials of 0.75 and 0.85 V, under acidic and basic conditions, respectively. During potential cycling, this DAMC displayed half-wave potential losses of only 25 and 5 mV under acidic and alkaline conditions after 3000 cycles, respectively, demonstrating its excellent stability. Single-cell Nafion-based proton exchange membrane fuel cell performance using this DAMC as the cathode catalyst showed a maximum power density of 225 mW cm-2 , almost close to that of most metal-N4 macrocycle-based catalysts. The present study showed that preservation of the defined CoN4 structure along with the cocatalytic Fe-Cx site synergistically acted as a dual ORR active center to boost overall ORR performance. The development of DAMC from a heterobimetallic CoN4-macrocyclic system using low-temperature pyrolysis is also advantageous for practical applications.

How does tautomerization affect the excited-state dynamics of an amino acid-derivatized corrole?

In the first two decades of the XXI century, corroles have emerged as an important class of porphyrinoids for photonics and biomedical photonics. In comparison with porphyrins, corroles have lower molecular symmetry and higher electron density, which leads to uniquely complementary properties. In macrocycles of free-base corroles, for example, three protons are distributed among four pyrrole nitrogens. It results in distinct tautomers that have different thermodynamic energies. Herein, we focus on the excited-state dynamics of a corrole modified with L-phenylalanine. The tautomerization in the singlet-excited state occurs in the timescales of about 10-100 picoseconds and exhibits substantial kinetic isotope effects. It, however, does not discernably affect nanosecond deactivation of the photoexcited corrole and its basic photophysics. Nevertheless, this excited-state tautomerization dynamics can strongly affect photoinduced processes with comparable or shorter timescales, considering the 100-meV energy differences between the tautomers in the excited state. The effects on the kinetics of charge transfer and energy transfer, initiated prior to reaching the equilibrium thermalization of the excited-state tautomer population, can be indeed substantial. Such considerations are crucially important in the design of systems for artificial photosynthesis and other forms of energy conversion and charge transduction.

Selective and Additive-Free Hydrogenation of Nitroarenes Mediated by a DMSO-Tagged Molecular Cobalt Corrole Catalyst.

We report on the first cobalt corrole that effectively mediates the homogeneous hydrogenation of structurally diverse nitroarenes to afford the corresponding amines. The given catalyst is easily assembled prior to use from 4-tert-butylbenzaldehyde and pyrrole followed by metalation of the resulting corrole macrocycle with cobalt(II) acetate. The thus-prepared complex is self-contained in that the hydrogenation protocol is free from the requirement for adding any auxiliary reagent to elicit the catalytic activity of the applied metal complex. Moreover, a containment system is not required for the assembly of the hydrogenation reaction set-up as both the autoclave and the reaction vessels are readily charged under a regular laboratory atmosphere.

Trifluoromethyl Hydrolysis En Route to Corroles with Increased Druglikeness.

Heme-like metal-chelating macrocycles, including expanded and contracted porphyrins, are of everlasting interest as drug candidates for numerous diseases. Still, all reported corrole derivatives (and most other heme analogues) do not fulfill the most basic standards expected for oral drug administration: a combination of low molecular weight and reasonable water solubility. We now disclose a very straightforward synthetic method that relies on surprisingly facile trifluoromethyl hydrolysis for gaining access to a new class of corroles that do satisfy all druglikeness criteria. The relevance is briefly exemplified for the iron corroles by demonstrating the ability to affect their association with plasma proteins and their performance for catalase-like decomposition of hydrogen peroxide.

Corroles: The Hitherto Elusive Parent Macrocycle and its Metal Complexes.

Corroles, macrocycles that owe their name to the cobalt-chelating prosthetic group of vitamin B12 and share numerous features with the iron-chelating porphyrin present in heme proteins/enzymes, constantly cross new boundaries ever since stable derivatives became easily accessible. Particularly important is the increasing utilization of corroles and the corresponding metal complexes for the benefit of mankind, in terms of new drug candidates for treating various diseases and as catalysts for sustainable energy relevant processes. One challenge is to gain access to the plain macrocycle, as to allow for full elucidation of the most fundamental properties of corroles. We have obtained the substituent-free corrole by several surprising and conceptually different pathways. Selected features of the corresponding metal complexes are illuminated, for pointing towards unique phenomena that are anticipated to largely expand the horizon regarding their utilization for contemporary catalysis.

Ligand Non-innocence and Single Molecular Spintronic Properties of AgII Dibenzocorrole Radical on Ag(111).

A facile method for the quantitative preparation of silver dibenzo-fused corrole Ag-1 is described. In contrast to the saddle conformation resolved by single-crystal X-ray analysis for Ag-1, it adopts an unprecedented domed geometry, with up and down orientations, when adsorbed on an Ag(111) surface. Sharp Kondo resonances near Fermi level, both at the corrole ligand and the silver center were observed by cryogenic STM, with relatively high Kondo temperature (172 K), providing evidence for a non-innocent AgII -corrole.2- species. Further investigation validates that benzene ring fusion and molecule-substrate interactions play pivotal roles in enhancing Ag(4d(x2 -y2 ))-corrole (π) orbital interactions, thereby stabilizing the open-shell singlet AgII -corrole.2- on Ag(111) surface. Moreover, this strategy used for constructing metal-free benzene-ring fused corrole ligand gives rise to inspiration of designing novel metal-corrole compound for multichannel molecular spintronics devices.

Palladium Complexes of Corroles and Sapphyrins.

Palladium complexes of corrole and sapphyrin were prepared in high yield and fully characterized. The corrole provides a tetradentate/trianionic square planar coordination sphere for PdII , charge balanced by pyridinium. Both one and two PdII ions may be accommodated by the pentapyrrolic skeleton of the sapphyrin, and in each case the macrocycle acts as bidentate/monoanionic ligand and the inner-sphere square planar geometry is completed by allyl anions coordinated in an η3 fashion. NMR spectroscopy and X-ray crystallography data analyses uncovered the presence of interesting stereoisomers due to the flexibility of the ally ligands and also the pyrrole ring(s) that is/are not involved in metal binding.

Corroles and Hexaphyrins: Synthesis and Application in Cancer Photodynamic Therapy.

Corroles and hexaphyrins are porphyrinoids with great potential for diverse applications. Like porphyrins, many of their applications are based on their unique capability to interact with light, i.e., based on their photophysical properties. Corroles have intense absorptions in the low-energy region of the uv-vis, while hexaphyrins have the capability to absorb light in the near-infrared (NIR) region, presenting photophysical features which are complementary to those of porphyrins. Despite the increasing interest in corroles and hexaphyrins in recent years, the full potential of both classes of compounds, regarding biological applications, has been hampered by their challenging synthesis. Herein, recent developments in the synthesis of corroles and hexaphyrins are reviewed, highlighting their potential application in photodynamic therapy.