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 -CF 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.

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.

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

An eight-member series of CF-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-CF groups on the macrocycle's periphery. The synthetic pathway to these CF-substituted derivatives, beginning with (tpfc)PF, involves two different initial routes: (i) direct electrophilic CF incorporation using FSOCFCOMe and copper iodide, or (ii) bromination to achieve the 2,3,8,17,18-pentabrominated compound using excess bromine in methanol.

Cell-Penetrating Protein/Corrole Nanoparticles.

Recent work has highlighted the potential of metallocorroles as versatile platforms for the development of drugs and imaging agents, since the bioavailability, physicochemical properties and therapeutic activity can be dramatically altered by metal ion substitution and/or functional group replacement. Significant advances in cancer treatment and imaging have been reported based on work with a water-soluble bis-sulfonated gallium corrole in both cellular and rodent-based models. We now show that cytotoxicities increase in the order Ga < Fe < Al < Mn < Sb < Au for bis-sulfonated corroles; and, importantly, that they correlate with metallocorrole affinities for very low density lipoprotein (VLDL), the main carrier of lipophilic drugs.

In vitro photodynamic inactivation (PDI) of pathogenic germs inducing onychomycosis.

Onychomycosis is a fungal nail infection caused primarily by the dermatophytes Trichophyton rubrum and Trichophyton interdigitale or, less frequently, by molds like Aspergillus spp. and Scopulariopsis brevicaulis. Photodynamic treatment of onychomycosis is considered a promising future therapy to overcome the frequent failure of currently used antifungals.

Rhodium Complexes of a New-Generation Sapphyrin: Unique Structures, Axial Chirality, and Catalysis.

Rhodium insertion into the new 5,10,15,20-tetrakis(trifluoromethyl)sapphyrin was found to be much more facile than for other analogues, owing to NH⋅⋅⋅F hydrogen-bonding interactions that stabilise the pyrrole-inverted structure characteristic of the metallated product. The thus-obtained rhodium(I) complexes have axial chirality, and the enantiomers were resolved. The latter were found to interconvert quite rapidly in a process that involves a tautomerisation-like movement of the metal fragment between the five N atoms.

Singlet oxygen luminescence kinetics under PDI relevant conditions of pathogenic dermatophytes and molds.

A treatment of onychomycosis using the photodynamic effect would be a favorable alternative to currently used antimycotic drugs. This study should be considered as a first step towards development and control of an efficient photodynamic inactivation of onychomycosis causative pathogens. Here, we evaluate the usage of time-resolved 2D singlet oxygen luminescence detection in combination with 2D fluorescence scanning as a tool to understand the behavior of the photosensitizer when applied to fungi on Petri dishes.

One-Pot Synthesis of Contracted and Expanded Porphyrins with meso-CF Groups.

Corrole and sapphyrin with the smallest meso-substituents reported so far were prepared in a one-pot synthesis that relies on a non-aldehydic precursor for introducing CF groups. The substantial amounts of products obtained by this facile pathway allowed for the full characterization of 5,10,15-tris(trifluoromethyl)corrole, the access to a variety of stable chelates thereof and investigations that disclose the unique structural and chemical properties induced by the CF substituents. The novel 5,10,15,20-tetra(trifluoromethyl)sapphyrin undergoes only single protonation, which according to its crystal structure is stabilized by favorable non-bonding F/H interaction between the meso-CF and the inverted pyrrolic NH.

Neurorescue by a ROS Decomposition Catalyst.

The effect of the bis-sulfonated iron(III) corrole (1-Fe), a potent decomposition catalyst of reactive oxygen species, on rescuing SN4741 cells that were damaged by 6-hydroxydopamine (6-OHDA) was investigated as an in vitro model system for studying cell death of dopaminergic neurons in the substantia nigra. Important findings that accompanied the ability to rescue dopaminergic neurons were increased expression of phenotypic dopaminergic proteins, such as tyrosine hydroxylase (TH) and dopamine transporter (DAT), which were significantly depleted upon 6-OHDA-mediated damage. 1-Fe also elevated expression levels of aldehyde dehydrogenase 1 (ALDH-1), previously disclosed as a cardinal protein in the pathogenesis of Parkinson's disease.

Development of Singlet Oxygen Luminescence Kinetics during the Photodynamic Inactivation of Green Algae.

Recent studies show the feasibility of photodynamic inactivation of green algae as a vital step towards an effective photodynamic suppression of biofilms by using functionalized surfaces. The investigation of the intrinsic mechanisms of photodynamic inactivation in green algae represents the next step in order to determine optimization parameters. The observation of singlet oxygen luminescence kinetics proved to be a very effective approach towards understanding mechanisms on a cellular level.

Porphyrins and Corroles with 2,6-Pyrimidyl Substituents.

Corroles and porphyrins with 2,6-pyrimidyl substituents are reported for the first time, together with the spectroscopic data and the crystal structures of the free-base porphyrin and of the phosphorus and cobalt complexes of the corrole.

Photodynamic inactivation of mold fungi spores by newly developed charged corroles.

The photodynamic effect, originally used in photodynamic therapy (PDT) for the treatment of different diseases, e.g. of cancer, has recently been introduced for the inactivation of bacteria.

Time-resolved electron paramagnetic resonance and phosphorescence studies of the lowest excited triplet states of Rh(III) corrole complexes.

The lowest excited triplet (T(1)) ππ* states of gallium (Ga) and various rhodium (Rh) 5,10,15-trispentafluorophenyl corroles (Cors) were studied in the liquid crystal (LC) E-7 and in rigid glasses by time-resolved electron paramagnetic resonance (TR-EPR) spectroscopy. The triplet sublevel energies were experimentally determined by the alignment of the molecules in the LC and by magnetophotoselection in the glass. The sublevel scheme of GaCor was determined by calculating the zero field splitting (ZFS) parameters.

Differential cytostatic and cytotoxic action of Metallocorroles against human cancer cells: potential platforms for anticancer drug development.

A gallium(III)-substituted amphiphilic corrole noncovalently associated with a targeting protein was previously found by us to confer promising cytotoxic and antitumor activities against a breast cancer cell line and a mouse xenograft breast cancer model. To further explore potential anticancer applications, the cytostatic and cytotoxic properties of six nontargeted metallocorroles were evaluated against seven human cancer cell lines. Results indicated that toxicity toward human cancer cells depended on the metal ion as well as corrole functional group substitution.

Metallocorroles as cytoprotective agents against oxidative and nitrative stress in cellular models of neurodegeneration.

Water-soluble iron, and manganese(III) complexes of corroles and porphyrins were examined with regard to their neuroprotective/neurorescue activities by using various neuronal cytotoxic models of oxidative and nitrative stress. The present study demonstrates that the metallocorroles significantly protect human neuroblastoma SH-SY5Y and mouse motor neuron-neuroblastoma fusion NSC-34 cell lines against neurotoxicity induced by either the peroxynitrite donor 3-morpholinosydnonimine or the parkinsonism-related neurotoxin 6-hydroxydopamine. The neuronal survival effect is further reflected by the prevention of 3-morpholinosydnonimine-induced protein nitration, inhibition of caspase 3 activation, as well as attenuation of 6-hydroxydopamine-mediated decrease in growth associated protein-43 levels.

Time-resolved electron paramagnetic resonance study of rhodium(III) corrole excited states.

Photoexcited states of three Rh(III) 5,10,15-tris(pentafluorophenyl)corroles coordinated by different axial ligands; namely, triphenylphosphine P(C(6)H(5))(3) group (1), pyridine C(6)H(5)N group (2), and two pyridine groups (3) were studied by X- and Q-band time-resolved electron paramagnetic resonance (TREPR) in frozen toluene and liquid crystal E-7. Transient mutations were utilized to identify multiplicity of the detected paramagnetic species. The spectra of 1 and 2 were assigned to triplet ((3)pipi*) states, while contributions of triplet ((3)dd and charge transfer (3)CT) and quintet ((5)dd) states were revealed in the spectrum of 3.

Superoxide dismutase activity of corrole metal complexes.

The first report regarding SOD activity of metallocorroles, investigated via the combination of the cytochrome C assay, pulse radiolysis, and electrochemistry, is used for identifying the main criteria needed for achieving good performance, as well as for elucidating mechanistic aspects of their action.

High-resolution NMR spectroscopic trends and assignment rules of metal-free, metallated and substituted corroles.

Major advances over the last few years have facilitated the synthesis of a large variety of meso-only substituted corroles that display interesting catalytic, therapeutic and photophysical properties. This work is the first to study extensively the NMR spectral characteristics of both metallated and non-metallated triarylcorroles in various organic solvents and provide guidelines for easy and reliable assignments of 1D 1H spectra from trends of J coupling constants and chemical shifts. An excellent correlation is found between C=C bond lengths derived from 3J(H,H) values and experimental lengths determined by x-ray crystallography of the same molecules.

Selective substitution of corroles: nitration, hydroformylation, and chlorosulfonation.

This work demonstrates the feasibility and power of electrophilic substitution on the peripheral carbon atoms of triarylcorroles as a synthetic tool to new derivatives. The large difference in the reactivity of the various carbon atoms on the macrocycle was shown to be of electronic rather than steric origin. A careful choice of reagents and a delicate control of reaction conditions allowed the selective syntheses of novel derivatives, in all of which substitution took place selectively in only the directly joined pyrrole rings of the macrocycle.

The First Direct Synthesis of Corroles from Pyrrole.

The solvent-free, catalyst-free condensation of pyrrole and aldehydes provides an extremely facile synthetic pathway to novel corroles [Eq. (1); Ar=C F , 2,6-F C H , 2,6-Cl C H ]. The product containing pentafluorophenyl groups is an excellent precursor of other derivatives, including an ionic, water-soluble corrole.