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.

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.

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.

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.

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.

Supramolecular Control of Photonic Response and Sensing of Nitricoxide using Iron(III) Corrole Monolayers and Their Stacks.

In this work, we assemble amphiphilic iron(III) corroles at air-water interfaces into well-defined quasi-two-dimensional molecular monolayers and theirs stacks for sensing of nitric oxide (NO). For this purpose, we use the Langmuir-Blodgett (LB) technique, which allows varying the packing density of iron(III) corroles anchored to the aqueous subphase via one molecular side. The stacks of ten down to three molecular monolayers on the front and back sides of the substrates are sufficiently optically dense to detect NO binding to the layers photometrically. This sensing with few layers demonstrates the potential for electronic detection, where very thin surface functionalizations enable efficient electronic communication between the layer and the (semi)conductor. Despite increasing optical densities, the spectral responses to NO exposure become smaller with increasing packing density until the collapse point of the monolayers is reached. This demonstrates that the highest molecular efficiency for binding and detection of NO is achieved at the smallest packing densities. This finding is relevant to all molecular sensor films with axial binding of analytes to the sensor molecules and demonstrates the advantage of sensor molecule assembly into monolayers on water-air interfaces using the LB technique.

Corrole Nanoparticles for Chemotherapy of Castration-Resistant Prostate Cancer and as Sonodynamic Agents for Pancreatic Cancer Treatment.

A nanoparticle-based system, composed of the gallium(III) complex of a minimally substituted corrole that is coated by transferrin as a targeting vehicle (3-Ga NPs), has been used for pre-clinical evaluation of its efficacy against human metastatic castration-resistant prostate cancer (mCRPC) tumor xenografts. All mice (N = 9) responded to a dose of 10 mg/kg, with a remarkable tumor growth inhibition of 400% following 2 weeks of treatment; Ames and hERG tests excluded potential concerns regarding mutagenicity and cardiotoxicity, respectively. Also demonstrated is the potential application of these 3-Ga NPs as sonodynamic agents for the preclinical treatment of pancreatic cancer. 10 mg/kg 3-Ga NPs combined with exposure to ultrasound waves (2 min of 1 MHz 0.1 w/cm2 twice a week) induced up to 77% tumor shrinkage. Consistently, tumor/tissue distribution and serum levels of 3-Ga NPs in mice revealed high tumor specificity, favorable pharmacokinetics, fast absorption, slower redistribution, and very slow drug clearance.

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.

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.

Doubly Stimulated Corrole for Organelle-Selective Antitumor Cytotoxicity.

Balancing between safety and efficacy of cancer chemotherapeutics is achievable by relying on internal and/or external stimuli for selective and on-demand antitumor cytotoxicity. We now introduce the difluorophosphorus(V) corrole PC-Im, a theranostic agent with a pH-sensitive N-methylimidazole moiety. Structure/activity relationships, via comparison with the permanently charged PC-ImM+ and the lipophilic PC, uncovered the exceptional features of PC-Im: nanoparticular and monomeric at neutral and low pH, respectively, 10-fold increased light-induced singlet oxygen production at acidic pH, internalization into malignant cells within minutes, and selective accumulation within lysosomes. Submillimolar PC-Im concentrations are tolerable in the dark, while illumination induces nanomolar cytotoxic effects due to a multiplicity of cellular deleterious events: endoplasmic reticulum fragmentation, lysosome fusion and exocytosis, calcium leakage, mitochondrial fission, and swelling. PC-Im emerges as an antitumor agent, whose potency is triggered by endogenous and exogenous stimuli, assuring its cytotoxicity will occur selectively upon lysosomal accumulation and solely upon light activation.

A chromophore-supported structural and functional model of dinuclear copper enzymes, for facilitating mechanism of action studies.

Type III dicopper centres are the heart of the reactive sites of enzymes that catalyze the oxidation of catechols. Numerous synthetic model complexes have been prepared to uncover the fundamental chemistry involved in these processes, but progress is still lagging much behind that for heme enzymes. One reason is that the latter gain very much from the informative spectroscopic features of their porphyrin-based metal-chelating ligand. We now introduce sapphyrin-chelated dicopper complexes and show that they may be isolated in different oxidation states and coordination geometries, with distinctive colors and electronic spectra due to the heme-like ligands. The dicopper(i) complex 1-Cu2 was characterized by 1H and 19F NMR spectroscopy of the metal-chelating sapphyrin, the oxygenated dicopper(ii) complex 1-Cu2O2 by EPR, and crystallographic data was obtained for the tetracopper(ii)-bis-sapphyrin complex [1-Cu2O2]2. This uncovered a non-heme [Cu4(OH)4]4- cluster, held together with the aid of two sapphyrin ligands, with structural features reminiscent of those of catechol oxidase. Biomimetic activity was demonstrated by the 1-Cu2O2 catalyzed aerobic oxidation of catechol to quinone; the sapphyrin ligand aided very much in gaining information about reactive intermediates and the rate-limiting step of the reaction.

Ultrafast Electron Transfer in a Self-Assembling Sulfonated Aluminum Corrole-Methylviologen Complex.

Photoinduced electron transfer systems can mimic certain features of natural photosynthetic reaction centers, which are crucial for solar energy production. Among other tetra-pyrroles, the versatile chemical and photophysical properties of corroles make them very promising donors applicable in donor-acceptor complexes. Here, we present a first comprehensive study of ultrafast photoinduced electron transfer in a self-assembling sulfonated aluminum corrole-methylviologen complex combining visible and mid-IR transient absorption spectroscopy. The noncovalent D-A association of the corrole-methylviologen complex has the great advantage that photoinduced charge separation becomes possible even though the back electron transfer (BET) rate is large. Initial forward electron transfer from corrole to methylviologen is observed on an ∼130 fs time scale. Subsequent back electron transfer takes place with τBET = (1.8 ± 0.5) ps, revealing very complex relaxation dynamics. Direct probing in the mid-IR allows us to unravel the back electron transfer and cooling dynamics/electronic reorganization. Upon tracing the dynamics of the methylviologen-radical marker band at 1640 cm-1 and the C═C stretching of corrole at around 1500 cm-1, we observe that large amounts of excess energy survive the back transfer, leading to the formation of hot ground state absorption. A closer examination of the signal after 300 ps, surviving the back transfer, exhibits a charge-separation yield of 10-15%.

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.

Hydrogen evolution catalysis by terminal molybdenum-oxo complexes.

Stable complexes with terminal triply bound metal-oxygen bonds are usually not considered as valuable catalysts for the hydrogen evolution reaction (HER). We now report the preparation of three conceptually different (oxo)molybdenum(V) corroles for testing if proton-assisted 2-electron reduction will lead to hyper-reactive molybdenum(III) capable of converting protons to hydrogen gas. The upto 670 mV differences in the [(oxo)Mo(IV)]-/[(oxo)Mo(III)]-2 redox potentials of the dissolved complexes came into effect by the catalytic onset potential for proton reduction thereby, significantly earlier than their reduction process in the absence of acids, but the two more promising complexes were not stable at practical conditions. Under heterogeneous conditions, the smallest and most electron-withdrawing catalyst did excel by all relevant criteria, including a 97% Faradaic efficiency for catalyzing HER from acidic water. This suggests complexes based on molybdenum, the only sustainable heavy transition metal, as catalysts for other yet unexplored green-energy-relevant processes.

A Synthetic SOD/Catalase Mimic Compound for the Treatment of ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. To date, the etiology of the disease is still unclear, with evidence of reactive oxygen species, mitochondrial dysfunction, iron homeostasis perturbation, protein misfolding and protein aggregation as key players in the pathology of the disease. Twenty percent of familial ALS and two percent of sporadic ALS instances are due to a mutation in Cu/Zn superoxide dismutase (SOD1). Sporadic and familial ALS affects the same neurons with similar pathology; therefore, the underlying hypothesis is that therapies effective in mutant SOD1 models could be translated to sporadic ALS. Corrole metal complexes have lately been identified as strong and potent catalytic antioxidants with beneficial effects in oxidative stress-related diseases such as Parkinson's disease, Alzheimer's disease, atherosclerosis, diabetes and its complications. One of the most promising candidates is the iron complex of an amphiphilic corrole, 1-Fe. In this study we used the SOD1 G93R mutant zebrafish ALS model to assess whether 1-Fe, as a potent catalytic antioxidant, displays any therapeutic merits in vivo. Our results show that 1-Fe caused a substantial increase in mutant zebrafish locomotor activity (up to 30%), bringing the locomotive abilities of the mutant treated group close to that of the wild type untreated group (50% more than the mutated untreated group). Furthermore, 1-Fe did not affect WT larvae locomotor activity, suggesting that 1-Fe enhances locomotor ability by targeting mechanisms underlying SOD1 ALS specifically. These results may pave the way for future development of 1-Fe as a viable treatment for ALS.

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.

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.

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).

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.