Reversible Reactions of Nitric Oxide with a Binuclear Iron(III) Nitrophorin Mimic.

Construction of functional synthetic systems that can reversibly bind and transport the most biologically important gaseous molecules, oxygen and nitric oxide (NO), remains a contemporary challenge. Myoglobin and nitrophorin perform these respective tasks employing a protein-embedded heme center where one axial iron site is occupied by a histidine residue and the other is available for small molecule ligation, structural features that are extremely difficult to mimic in protein-free environments. Indeed, the hitherto reported designs rely on sophisticated multistep syntheses for limiting access to one of the two axial coordination sites in small molecules. We have shown previously that binuclear Ga(III) and Al(III) corroles have available axial sites, and now report a redox-active binuclear Fe(III) corrole, (1-Fe)2 , in which each (corrolato)Fe(III) center is 5-coordinate, with one axial site occupied by an imidazole from the other corrole. The binuclear structure is further stabilized by attractive forces between the corrole π systems. Reaction of NO with (1-Fe)2 affords mononuclear iron nitrosyls, and of functional relevance, the reaction is reversible: nitric oxide is released upon purging the nitrosyls with inert gases, thereby restoring (1-Fe)2 in solutions or films.

Redox Active Ligands for Catalyzing the Hydrogen Evolution Reaction.

Boron subphthalocyanines with chloride and fluoride axial ligands and three antimony complexes chelated by corroles that differ in size and electron-richness were examined as electrocatalysts for reduction of protons to hydrogen. Experiment- and computation-based investigations revealed that all redox events are ligand-centered and that the meso-C of the corroles and the peripheral N atoms of the subphthalocyanines are the largely preferred proton-binding sites.

Surprising Route to a Monoazaporphyrin and Full Characterization of Its Complexes with Five Different 3d Metals.

In the search for mild agents for the oxidative cyclization of tetrapyrromethane to the corresponding corrole, we discovered a route that leads to a monoazaporphyrin with three meso-CF3 groups. Optimization studies that allowed access to appreciable amounts of this new macrocycle paved the way for the preparation of its cobalt, copper, nickel, zinc, and iron complexes. All complexes were fully characterized by various spectroscopic methods and X-ray crystallography. Their photophysical and electrochemical properties were determined and compared to those of analogous porphyrins in order to deduce the effect of the peripheral N atom. Considering the global efforts for designing efficient alternatives to platinum group metal (PGM) catalysts, they were also absorbed onto a porous carbon electrode material and studied as electrocatalysts for the oxygen reduction reaction (ORR). The cobalt complex was found to be operative at a quite positive catalytic onset potential and with good selectivity for the desirable 4-electrons/4-protons pathway.

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.

Milestones in corrole chemistry: historical ligand syntheses and post-functionalization.

Corroles are synthetic porphyrin analogs that contain one meso carbon atom lesser and bear a trianionic N4 metal-chelating core. They require in-depth preparative chemistry, demonstrate unique coordination chemistry and have impressive and diverse physical properties, and these are commonly compared to their respective porphyrins. The corrole's macrocyclic system is inherently electron rich and chelates metal ions in a more compact, less symmetric tetranitrogen cavity compared to that of porphyrins. Herein, we cover the highlights of the corrole research through the decades by first reviewing, in a chronological sense, multi-step syntheses; some routes have since been discontinued. This is followed by describing post-functionalization of already formed corroles via reactions performed on either the macrocycle's periphery or the inner nitrogen atoms or on the existing substituents. We do also mention milestones in literature reviewing, publication of encyclopedias, and the creation of professional organizations and conferences (ICPP) which make up the corrole/porphyrin research landscape. Also highlighted are still existing challenges and future perspectives.

Milestones and Most Recent Advances in Corrole's Science and Technology.

The renaissance in corrole chemistry is strongly correlated with synthetic breakthroughs that started in 1999, regarding the one-pot rather than multistep syntheses of this heme-like N4 macrocycle. This largely improved synthetic accessibility allowed for technological advances wherein the corresponding metal complexes have since been introduced as key elements. Great emphasis was devoted to the elucidation of the unique fundamental features that distinguish corrole ligands, among them outstanding electron donation (σ by the N atoms and π by the macrocycle) to transition metals chelated by them. Such investigations remain crucial for enabling the by-demand tuning of metallocorrole properties for distinctly different applications. These range from the catalysis of organic reactions, through bioimaging and disease prevention/treatment strategies, to photo- and electrocatalysis for clean energy. Surveyed are the original reports that impacted these developments, together with some of the most recent advances.

Size and Electronic Effects on the Performance of (Corrolato)cobalt-Modified Electrodes for Oxygen Reduction Reaction Catalysis.

Considering the worldwide efforts for designing catalysts that are not based on platinum group metals while still reserving the many advantages thereof, this study focused on the many variables that dictate the performance of cathodes used for fuel cells, regarding the efficient and selective reduction of oxygen to water. This was done by investigating two kinds of porous carbon electrodes, modified by molecular cobalt(III) complexes chelated by corroles that differ very much in size and electron-withdrawing capability. Examination of the electronic effect uncovered shifts in the CoII/CoIII redox potentials and also large differences in the affinity of the cobalt center to external ligands. Spontaneous absorption of the catalysts was found to depend on the size of the corrole's substituents (C6F5 ≫ CF3 ≫ H) and the metal's axial ligands (PPh3 versus pyridine), as well as on the porosity of the carbon electrodes (BP2000 > Vulcan). The better-performing cobalt-based catalysts were almost as active and selective as 20% platinum on Vulcan in terms of the onset potential and the only 2-10% undesirable formation of hydrogen peroxide. Durability was also addressed by using the best-performing modified cathode in a proper anion-exchange membrane fuel cell setup, revealing very little voltage change during 12 h of operation.

Electronic Coupling and Electrocatalysis in Redox Active Fused Iron Corroles.

Conjugated arrays composed of corrole macrocycles are increasingly more common, but their chemistry still lags behind that of their porphyrin counterparts. Here, we report on the insertion of iron(III) into a ß,ß-fused corrole dimer and on the electronic effects that this redox active metal center has on the already rich coordination chemistry of [H3tpfc] COT, where COT = cyclo-octatetraene and tpfc = tris(pentafluorophenyl)corrole. Synthetic manipulations were performed for the isolation and full characterization of both the 5-coordinate [FeIIItpfc(py)]2COT and 6-coordinate [FeIIItpfc(py)2]2COT, with one and two axial pyridine ligands per metal, respectively. X-Ray crystallography reveals a dome-shaped structure for [FeIIItpfc(py)]2COT and a perfectly planar geometry which (surprisingly at first) is also characterized by shorter Fe-N (corrole) and Fe-N (pyridine) distances. Computational investigations clarify that the structural phenomena are due to a change in the iron(III) spin state from intermediate (S = 3/2) to low (S = 1/2), and that both the 5- and 6-coordinated complexes are enthalpically favored. Yet, in contrast to iron(III) porphyrins, the formation enthalpy for the coordination of the first pyridine to Fe(III) corrole is more negative than that of the second pyridine coordination. Possible interactions between the two corrole subunits and the chelated iron ions were examined by UV-Vis spectroscopy, electrochemical techniques, and density functional theory (DFT). The large differences in the electronic spectra of the dimer relative to the monomer are concluded to be due to a reduced electronic gap, owing to the extensive electron delocalization through the fusing bridge. A cathodic sweep for the dimer discloses two redox processes, separated by 230 mV. The DFT self-consistent charge density for the neutral and cationic states (1- and 2-electron oxidized) reveals that the holes are localized on the macrocycle. A different picture emerges from the reduction process, where both the electrochemistry and the calculated charge density point toward two consecutive electron transfers with similar energetics, indicative of very weak electron communication between the two redox active iron(III) sites. The binuclear complex was determined to be a much better catalyst for the electrochemical hydrogen evolution reaction (HER) than the analogous mononuclear corrole.

Dimeric Corrole Analogs of Chlorophyll Special Pairs.

Chlorophyll special pairs in photosynthetic reaction centers function as both exciton acceptors and primary electron donors. Although the macrocyclic natural pigments contain Mg(II), the central metal in most synthetic analogs is Zn(II). Here we report that insertion of either Al(III) or Ga(III) into an imidazole-substituted corrole affords an exceptionally robust photoactive dimer. Notably, attractive electronic interactions between dimer subunits are relatively strong, as documented by signature changes in NMR and electronic absorption spectra, as well as by cyclic voltammetry, where two well-separated reversible redox couples were observed. EPR spectra of one-electron oxidized dimers closely mimic those of native special pairs, and strong through-space interactions between corrole subunits inferred from spectroscopic and electrochemical data are further supported by crystal structure analyses (3 Å interplanar distances, 5 Å lateral shifts, and 6 Å metal to metal distances).

Solvent Effects on the Phosphorescence of Gold(III) Complexes Chelated by ß-Multisubstituted Corroles.

A set of gold corrole complexes containing four different ß-substituent groups (Br/I/CF3), namely, 4Br-Au, 4I-Au, and 4CF3-Au, were investigated; all showed room temperature phosphorescence. The phosphorescence quantum yields of the corroles were determined using tetraphenylporphyrin as a reference: Φph (4I-Au, 0.75%) > Φph (4Br-Au, 0.64%) > Φph (4CF3-Au, 0.38%). 4CF3-Au exhibited near-IR emission (858 nm, aerobic); absorbance intensity for the Q-band was higher than that for the Soret band. Complex 4I-Au showed a longer phosphorescence lifetime (82 µs) compared to those of 4Br-Au (53 µs) and 4CF3-Au (28 µs; N2, tol). Thermally activated delayed fluorescence (TADF) emission of 4I/Br-Au complexes was observed: stronger emission intensity correlated with increasing temperature. Good negative correlations for 4I/Br-Au were observed between the Soret band absorption energy and the solvent polarizability: excited states of 4I/Br-Au are more polar than their ground states. TD-DFT calculations revealed very fast intersystem crossing (ISC) rate constants, 2.20 × 1012 s-1 (4CF3-Au) > 1.96 × 1011 s-1 (4Br-Au) > 1.15 × 1011 s-1 (4I-Au), and importantly, the reverse intersystem crossing (rISC) rate constants are determined as 1.68 × 107 s-1 (4I-Au) > 2.40 × 103 s-1 (4Br-Au) ≫ 8.09 × 10-8 s-1 (4CF3-Au). The exceptionally low rISC rate constant of 4CF3-Au is attributed to its more steric and deformed structure bearing a larger energy gap between the S1 and T1 states.

Custom Tokenization Dictionary, CUSTODI: A General, Fast, and Reversible Data-Driven Representation and Regressor.

Custom tokenization dictionary (CUSTODI) is introduced as a novel way for tackling the problem of molecular representations, and especially the challenge of molecular property prediction. Herein, the motivational theory and the actual representation and model are presented and shown to have performance that is in line with benchmark methodologies. The uniqueness of CUSTODI is its applicability on small training sets and the developed theory suggests its possible use for a-priori estimation of future fit quality on any given dataset, regardless of the method used for fitting.

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.

Elucidation of Factors That Govern the 2e-/2H+ vs 4e-/4H+ Selectivity of Water Oxidation by a Cobalt Corrole.

Considering the importance of water splitting as the best solution for clean and renewable energy, the worldwide efforts for development of increasingly active molecular water oxidation catalysts must be accompanied by studies that focus on elucidating the mode of actions and catalytic pathways. One crucial challenge remains the elucidation of the factors that determine the selectivity of water oxidation by the desired 4e-/4H+ pathway that leads to O2 rather than by 2e-/2H+ to H2O2. We now show that water oxidation with the cobalt-corrole CoBr8 as electrocatalyst affords H2O2 as the main product in homogeneous solutions, while heterogeneous water oxidation by the same catalyst leads exclusively to oxygen. Experimental and computation-based investigations of the species formed during the process uncover the formation of a Co(III)-superoxide intermediate and its preceding high-valent Co-oxyl complex. The competition between the base-catalyzed hydrolysis of Co(III)-hydroperoxide [Co(III)-OOH]- to release H2O2 and the electrochemical oxidation of the same to release O2 via [Co(III)-O2•]- is identified as the key step determining the selectivity of water oxidation.

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.

Clean Ar-Me conversion to Ar-aldehyde with the aid of carefully designed metallocorrole photocatalysts.

Toluene, p-xylene and mesitylene were cleanly converted to their corresponding monoaldehydes via mild photooxygenation utilizing transition metal and main group ß-CF3-substituted corroles. Aldehyde yield increased as more electron-donating CH3 groups are present on the substrate. 4-P was most efficient (TON ∼ 1072, mesitylene) via the singlet oxygen vis the superoxide mechanism.

Axial/Peripheral Chloride/Fluoride-Substituted Boron Subphthalocyanines as Electron Acceptors.

Chloroboron subphthalocyanines (Cl-BsubPc) are robust compounds that can be readily modified at the axial and peripheral positions. Peripherally chlorinated derivatives were recently found to be advantageous regarding integration into organic electronic devices. We now report on the effects of fluorides introduced on both the peripheral and axial positions of BsubPcs. Specific attention on the reduction of these compounds revealed that the much fewer electronegative chlorides still shift the redox potentials as much as fluorides. The main advantage of the fluorinated derivatives was deduced to be their stability, allowing for the spectroscopic characterization of mono-anionic and even bis-anionic subphthalocyanines. This study sets the precedence for further tuning of the electrochemical properties of BsubPcs through molecular design, thus increasing their applicability regarding organic electronic devices that undergo multiple redox cycles during operational lifetime.

Tuning Chemical and Physical Properties of Phosphorus Corroles for Advanced Applications.

Although the affinity of metallocorroles to axial ligands is quite low, this is not the case when the chelated element is phosphorus. This work is hence focused on the mechanism of ligand exchange of six-coordinate phosphorus corroles as a tool for affecting their chemical and physical properties. These fundamental investigations allowed for the development of facile methodologies for the synthesis of a large series of complexes and the establishment of several new structure/activity profiles that may be used to understand and predict spectroscopic features and for tailor-made modification of photophysical and electrochemical properties. This is exemplified by the facile access to complexes with terminal groups that are of large potential for practical applications based on click chemistry, optical imaging, and surface science.

Structures and Spectroscopic Properties of Metallocorrole Nanoparticles.

In aqueous media, hydrophobic metallocorroles form nanoparticles that are potential theranostic anticancer agents. We have analyzed the electronic and Raman spectra of Al(III), Ga(III), and Au(III) corrole nanoparticles (and made comparisons with DFT-validated assignments of the IR spectra of corresponding monomers) in order to estimate the strengths of corrole-corrole electronic couplings in these assemblies. We find that these spectra are virtually unchanged upon aggregation, confirming that the intermolecular interactions in these nanoparticles are very weak.

Maximizing Property Tuning of Phosphorus Corrole Photocatalysts through a Trifluoromethylation Approach.

An eight-member series of CF3-substituted difluorophosphorus corroles was prepared for establishing a structure-activity profile of these high-potential photosensitizers. It consisted of preparing all four possible isomers of the monosubstituted corrole and complexes with 2-, 3-, 4-, and 5-CF3 groups on the macrocycle's periphery. The synthetic pathway to these CF3-substituted derivatives, beginning with (tpfc)PF2, involves two different initial routes: (i) direct electrophilic CF3 incorporation using FSO2CF2CO2Me and copper iodide, or (ii) bromination to achieve the 2,3,8,17,18-pentabrominated compound using excess bromine in methanol. Crystallographic investigations revealed that distortion of the original planar macrocycle is evident even in the monosubstituted case and that it becomes truly severe for the penta-CF3-substituted derivative 5. There is a shift in redox potentials of about 193 mV per -CF3 group, which decreases to only 120 mV for the fifth one in 5. Differences in the electronic spectra suggest that the Gouterman four orbital model decreases in relevance upon gradual -CF3 substitution, a conclusion that was corroborated by DFT calculations. The very significant energy lowering of the frontier orbitals suggested that photoexcitation should lead to a highly oxidizing photocatalyst. This hypothesis was proven true by finding that the most synthetically accessible CF3-substituted derivative is an excellent catalyst for the photoinduced conversion of bromide to bromine (phenol, toluene, and benzene assay).