CoCorrole-Functionalized PCN-222 for Carbon Monoxide Selective Adsorption.

The high risk of CO poisoning justifies the need for indoor air quality control and warning systems based on the detection of low concentrations (ppm-ppb) of CO. Cobalt corrole complexes selectively bind CO vs. O2, CO2, N2, opening new fields of applications. By combining the CO chemisorption properties of cobalt corroles with the known sorption capacity of MOFs, we hope to obtain high performance sensing materials for CO detection. In addition, the exposed metal sites of MOFs lead to CO2 physisorption, allowing the co-detection of CO and CO2. In this work, PCN-222 a stable Zr-based MOF made from Ni(TCPP) with natural vacancies has been used as a porous matrix for the grafting of electron-poor metallocorroles. The materials were characterized by powder XRD, SEM and optical microscopy, BET analyses and gas adsorption measurements at 298 K. No degradation of the crystalline structure of PCN-222 was observed. At 1 atm, the adsorbed CO(g) volumes measured for the best materials were 12.15 cm3 g-1 and 14.01 cm3 g-1 for CoCorr2@PCN-222 and CoCorr3@PCN-222 respectively, and both materials exhibited high CO chemisorption and selectivity against O2, N2, and CO2 at low pressure due to the highest energy of the chemisorption process vs physisorption. (198 Words).

Synthesis and characterization of new acid-functionalized porphyrins displaying antimicrobial activity against gram positive bacteria, yeasts and filamentous fungi with or without ultra-high irradiance.

The antimicrobial activity of new acid-functionalized porphyrins, with or without ultra-high irradiance, was investigated. Antibacterial efficacy was evaluated against Staphylococcus aureus (methicillin-resistant or methicillin-sensitive strains) and antifungal efficacy was evaluated against the yeast Candida albicans and the filamentous fungi Aspergillus fumigatus. Overall, the porphyrins tested are more effective against S. aureus. The best results were obtained with zinc diacid porphyrins 4 and 5 after only 3 min of ultra-high irradiation (500 mW/cm2, 405 nm), demonstrating that acid-functionalized porphyrins are promising as novel antimicrobial drugs for surface disinfection.

Inverse Hypercorroles.

Ground-state and time-dependent density functional theory (TDDFT) calculations with the long-range-corrected, Coulomb-attenuating CAMY-B3LYP exchange-correlation functional and large, all-electron STO-TZ2P basis sets have been used to examine the potential "inverse hypercorrole" character of meso-p-nitrophenyl-appended dicyanidocobalt(III) corrole dianions. The effect is most dramatic for 5,15-bis(p-nitrophenyl) derivatives, where it manifests itself in intense NIR absorptions. The 10-aryl groups in these complexes play a modulatory role, as evinced by experimental UV-visible spectroscopic and electrochemical data for a series of 5,15-bis(p-nitrophenyl) dicyanidocobalt(III) corroles. TDDFT (CAMY-B3LYP) calculations ascribe these features clearly to a transition from the corrole's a2u-like HOMO (retaining the D4h irrep used for metalloporphyrins) to a nitrophenyl-based LUMO. The outward nature of this transition contrasts with the usual phenyl-to-macrocycle direction of charge transfer transitions in many hyperporphyrins and hypercorroles; thus, the complexes studied are aptly described as inverse hypercorroles.

Altering the Site of Electron Abstraction in Cobalt Corroles via meso-Trifluoromethyl Substituents.

A mono-DMSO cobalt meso-CF3 corrole, formulated as (CF3)3CorCo(DMSO), where (CF3)3Cor is the trianion of 5,10,15-tris(trifluoromethyl)corrole, was synthesized and characterized as to its spectral and electrochemical properties in nonaqueous media with a focus on its coordination chemistry and electronic structure. Cyclic voltammetric measurements showed more facile reductions and difficult oxidations compared to the cobalt triarylcorrole possessing p-CF3Ph units at the meso-positions, a result consistent with the enhanced inductive effect of the electron-withdrawing trifluoromethyl substituents linked directly at the meso-carbon atoms of the macrocycle. The effects of DMSO, pyridine, and cyanide anions (CN-) on the electrochemistry and spectral properties of the compound were investigated, and it was found that only two molar equivalents are needed to form the bis-CN adduct, which exhibited two 1-electron oxidations at 0.27 and 0.95 V vs saturated calomel electrode (SCE) in CH2Cl2/0.1 M TBAP. The sites of electron transfer in the first oxidation and reduction were investigated by spectroelectrochemistry and confirmed that the first electron addition affords a Cor3-CoII complex under all solution conditions independent of the initial coordination and/or electronic configuration (i.e., innocent Cor3-CoIII or noninnocent Cor•2-CoII). In contrast, data for the first oxidation suggests that the site of electron abstraction (ligand or metal) depended upon coordination of the neutral and in situ generated complexes under the various solution conditions, leading to a Co(IV)-corrole3- product for both the bis-pyridine and bis-cyanide adducts.

Evaluation of carboxylic acid-derivatized corroles as novel gram-positive antibacterial agents under non-photodynamic inactivation conditions.

Herein, we report the synthesis and evaluation of carboxylic acid corroles bearing either one, two, three of four carboxylic groups as gram-positive antibacterial agents against two strains of S. aureus, one methicillin-sensible (MSSA) and the other methicillin-resistant (MRSA). Lead compounds 5 and 6 show low minimum inhibitory concentrations (MICs) of 0.78 µg/mL against both MSSA and MRSA. These molecules, previously underexplored as antibacterial agents, can now serve as a new scaffold for antimicrobial development.

Cobalt tris(4-vinylphenyl)corrole: out of the frying pan into the polymer.

A novel cobalt corrole bearing 4-vinylphenyl groups at the 5,10,15-meso-positions of the macrocycle has been synthesized from tris(4-bromophenyl)corrole using a Suzuki coupling reaction. The spectral and electrochemical properties are reported in CH2Cl2 along with its ability to form a highly stable six-coordinate complex and cross-linked corrole-based polymer in a 59% yield.

Hypercorroles Formed via the Tail that Wagged the Dog: Charge Transfer Interactions from Innocent Corroles to Meso-Nitrophenyl Substituents.

A series of cobalt nitrophenylcorroles were spectrally characterized in CH2Cl2, and under certain solution conditions, several compounds were shown to exhibit hypercorrole spectra resulting from charge transfer interactions from the corrole π-system to the redox-active meso-NO2Ph substituents. The resulting spectral pattern has not previously been reported for metallocorroles and in the case of the cobalt derivatives was shown to depend upon the number and position of the meso-nitrophenyl groups on the macrocycle, the position of the NO2 substituent on the meso-phenyl ring(s) (para or meta), and the electronic structure of the corrole, which can exist in its innocent or noninnocent form depending in large part upon the type and number of axial ligands. Cobalt corroles bearing p-nitrophenyl groups at the 5,15- or 5,10,15-positions of the macrocycle exhibited the most marked hypercorrole spectra under solution conditions where the complex was innocent (i.e., Cor3-CoIII), and a systematic analysis of the spectral data suggests the root of this perturbation to be a corrole-to-aryl interaction (i.e., ligand-to-ligand charge transfer or LLCT). The largest interaction between the π-system and the NO2Ph substituents was seen upon coordination of anionic cyanide (CN-) axial ligands to the Co(III) center of the bis-(CN-)-5,15-dinitrophenyl derivative, resulting in a cobalt hypercorrole spectrum where the broad Q-band was red-shifted even further into the NIR region and located at 795 nm in CH2Cl2 and 827 nm in pyridine. Cyclic voltammetry of the bis-CN- adducts showed that the first electrons are added to the LUMOs of the p-NO2Ph substituents rather than the corrole, while the same orbitals for the mono-CN- adducts are nearly degenerate. This redox behavior contrasts with what is seen for the noninnocent nitrophenyl corroles having "normal" unperturbed UV-vis spectra where the first reduction involves the π-system of the macrocycle, followed by reduction of the p-NO2Ph groups at more negative potentials.

Identifying G-Quadruplex-DNA-Disrupting Small Molecules.

The quest for small molecules that strongly bind to G-quadruplex-DNA (G4), so-called G4 ligands, has invigorated the G4 research field from its very inception. Massive efforts have been invested to discover or rationally design G4 ligands, evaluate their G4-interacting properties in vitro through a series of now widely accepted and routinely implemented assays, and use them as innovative chemical biology tools to interrogate cellular networks that might involve G4s. In sharp contrast, only uncoordinated efforts aimed at developing small molecules that destabilize G4s have been invested to date, even though it is now recognized that such molecular tools would have tremendous application in neurobiology as many genetic and age-related diseases are caused by an overrepresentation of G4s. Herein, we report on our efforts to develop in vitro assays to reliably identify molecules able to destabilize G4s. This workflow comprises the newly designed G4-unfold assay, adapted from the G4-helicase assay implemented with Pif1, as well as a series of biophysical and biochemical techniques classically used to study G4/ligand interactions (CD, UV-vis, PAGE, and FRET-melting), and a qPCR stop assay, adapted from a Taq-based protocol recently used to identify G4s in the genomic DNA of Schizosaccharomyces pombe. This unique, multipronged approach leads to the characterization of a phenylpyrrolocytosine (PhpC)-based G-clamp analog as a prototype of G4-disrupting small molecule whose properties are validated through many different and complementary in vitro evaluations.

Antipoxvirus Activity Evaluation of Optimized Corroles Based on Development of Autofluorescent ANCHOR Myxoma Virus.

A series of 43 antiviral corrole-based molecules have been tested on myxoma virus (Lausanne-like T1MYXV strain). An autofluorescent MYXV, with an ANCHOR cassette, has been used for the studies. A2B-fluorocorroles display various toxicities, from 40 being very toxic (CC50 = 1.7 µM) to nontoxic 38 (CC50 > 50 µM), whereas A3-fluorocorroles, with one to three fluorine atoms, are not toxic (with the exception of corroles 9, 10, and 22). In vitro, these compounds show a good selectivity index when used alone. Corrole 35 seems to be the most promising compound, which displays a high selectivity index with the lowest IC50. Interestingly, this "Hit" corrole is easy to synthesize in a two-step reaction. Upscaling production up to 25 g has been carried out for in vivo tests. In vivo studies on New Zealand white rabbits infected with myxoma virus show that symptoms are delayed and animal weight is increased upon treatment, while no acute toxicity of the corrole molecule was detected.

Multimodal Theranostic Cyanine-Conjugated Gadolinium(III) Complex for In Vivo Imaging of Amyloid-ß in an Alzheimer's Disease Mouse Model.

Despite the wide use of magnetic resonance imaging (MRI) as a clinical diagnostic tool, there are still no clinically approved MRI contrast agents that can be applied for cerebral Alzheimer's disease (AD) biomarker imaging. We report here the design and development of the first amyloid-ß (Aß)-targeted, blood-brain barrier (BBB) penetrable theranostic Gd(DOTA)-cyanine dyad, which was synthesized by the conjugation of Gd(DOTA) complex and carbazole-based cyanine dye by the copper(I)-catalyzed azide-alkyne cycloaddition click reaction for imaging of Aß in vivo and ex vivo in AD mouse models. This dyad, as a multimodal probe, possesses desirable multifunctional properties, including good biocompatibility, low cytotoxicity, high Aß selectivity, strong fluorescence enhancement upon binding with Aß species, good paramagnetic properties, high stability, good BBB penetrability, and fast elimination from the mouse. The longitudinal relaxivity (r1) of the dyad was found to be 4.42 mM-1 s-1 at 3 T, suggesting it to be promising as a T1-weighted MRI contrast agent. The probe has been successfully demonstrated to be able to be applied for one- and two-photon excited fluorescence and magnetic resonance (MR) imaging of Aß in transgenic mouse models of AD. In addition, it can inhibit Aß aggregation, protect against toxicity induced by Aß, and suppress Aß-induced reactive oxygen species (ROS) production. Our results demonstrate the highly promising theranostic capability of the dyad for diagnosis and therapy of AD and extraordinary potential for MRI of Aß in humans.

Solvent and Anion Effects on the Electrochemistry of Manganese Dipyrrin-Bisphenols.

A series of "N2O2-type" manganese dipyrrin-bisphenols (DPP), formulated as (Ar)DPPMn, where Ar = pentafluorophenyl (F5Ph), phenyl (Ph), or mesityl (Mes), were electrochemically and spectroscopically characterized in nonaqueous media with and without added anions in the form of tetrabutylammonium salts (TBAX where X = ClO4-, PF6-, BF4-, F-, Cl-, OH-, or CN-). Two major one-electron reductions are observed under most solution conditions, the first of which is assigned as a MnIII/II process and the second as electron addition to the π-ring system as confirmed by spectroelectrochemistry. Each MnIII complex also exhibits one or two one-electron oxidations, the exact number depending upon the positive potential limit of the electrochemical solvent. The two oxidations are separated by 580-590 mV in CH3CN containing 0.1 M TBAPF6 and are assigned as π-ring-centered electron transfers to stepwise form a (Ar)DPPMnIII π-cation radical and dication under these solution conditions. Comparisons are made between redox properties of (Ar)DPPMn and manganese(III) porphyrins, corroles, and corrolazines each of which contains an innocent trianionic complexing ligand. The redox behavior and spectroscopic properties of [(Ar)DPPMn]n where n = 0, -1, or +1 are also compared to that of other structurally related [(Ar)DPPM]n complexes under similar solution conditions where M = CoII, CuII, BIII, or AuIII.

Porous materials applied to biomarker sensing in exhaled breath for monitoring and detecting non-invasive pathologies.

The quantification of specific gases among thousands of VOCs (Volatile Organic Compounds) present in the human breath at the ppm/ppb level can be used to evidence the presence of diseases in the human body. The detection of these biomarkers in human exhaled breath through a noninvasive approach is an important field of research that is still attracting significant attention to this day. A portable device working at room temperature and usable directly on exhaled breath samples is still a challenge requiring a sensing material with high performances. The rich composition of the human breath implies that the sensing material must be highly selective and sensitive (ppm/ppb) in high relative humidity (RH) conditions and preferably at room temperature. The present work intends to provide a review on recent works in this application field through the use of porous materials and discuss the importance of Metal Organic Frameworks (MOFs) for such application. MOFs are highly porous crystalline materials often used for gas detection and capture, thus raising questions about their potential for detection in exhaled breath.

Old Dog, New Tricks: Innocent, Five-coordinate Cyanocobalt Corroles.

Three mono-CN ligated anionic cobalt A3-triarylcorroles were synthesized and investigated as to their spectroscopic and electrochemical properties in CH2Cl2, pyridine (Py), and dimethyl sulfoxide (DMSO). The newly synthesized corroles provide the first examples of air-stable cobalt corroles with an anionic axial ligand and are represented as [(Ar)3CorCoIII(CN)]-TBA+, where Cor is the trivalent corrole macrocycle, Ar is p-(CN)Ph, p-(CF3)Ph, or p-(OMe)Ph, and TBA+ is the tetra-n-butylammonium (TBA) cation. Multiple redox reactions are observed for each mono-CN derivative with a key feature being a more facile first oxidation and a more difficult first reduction in all three solvents as compared to all previously examined corroles with similar meso- and ß-pyrrole substituents. Formation constants (log K) for conversion of the five-coordinate mono-CN complex to its six-coordinate bis-CN form ranged from 102.8 for Ar = p-(OMe)Ph to 104.7 for Ar = p-(CN)Ph in DMSO as determined by spectroscopic methodologies. The in situ generated bis-CN complexes, represented as [(Ar)3CorCoIII(CN)2]2-(TBA+)2, and the mixed ligand complexes, represented as [(Ar)3CorCoIII(CN)(Py)]-TBA+, were also investigated as to their electrochemical and spectroscopic properties. UV-visible spectra and electrode reactions of the synthesized mono-CN derivatives are compared with the neutral mono-DMSO cobalt corrole complexes and the in situ generated bis-CN and bis-Py complexes, and the noninnocent (or innocent) nature of each cobalt corrole system is addressed. The data demonstrate the ability of the CN- axial ligand(s) to stabilize the high-valent forms of the metallocorrole, leading to systems with innocent macrocyclic ligands. Although a number of six-coordinate cobalt(III) corroles with N-donor ligands were characterized in the solid state, a dissociation of one axial ligand readily occurs in nonaqueous solvents, and this behavior contrasts with the high stability of the currently studied bis-CN adducts in CH2Cl2, pyridine, or DMSO. Linear free energy relationships were elucidated between the meso-phenyl Hammett substituent constants (Σσ) and the measured binding constants, the redox potentials, and the energy of the band positions in the mono-CN and bis-CN complexes in their neutral or singly oxidized forms, revealing highly predictable trends in the physicochemical properties of the anionic corroles.

A3- and A2B-nitrocorroles: synthesis and antiviral activity evaluation against human cytomegalovirus infection.

Human cytomegalovirus (hCMV) is responsible for several pathologies impacting immunocompromised patients and can trigger life-threatening infection. Several antivirals are available and are used in the clinic, but hCMV resistant strains have appeared and patients have encountered therapeutic failure. Hence, there is a constant need for new best in class or first in class antiviral molecules. We have previously shown that nitrocorroles could be used as a potent anti-hCMV agent without acute toxicity in mice. They therefore represent an excellent platform to perform structure-activity relationship (SAR) studies and to increase efficiency or reduce toxicity. We have generated original A2B- and A3-substituted nitrocorroles and have discovered optimized compounds with selectivity indices above 200. These compounds are easily synthesized in only one to two-step reactions; they are up-scalable and cost efficient. They are therefore excellent candidates for hCMV therapies and they pave the way for a new generation of molecules.

A3- and A2B-fluorocorroles: synthesis, X-ray characterization and antiviral activity evaluation against human cytomegalovirus infection.

Twenty-nine fluorinated corroles were prepared, spectroscopically characterized, and studied for their antiviral activity against human cytomegalovirus infection. Six corroles were also fully characterized by X-ray crystallography giving insights on their geometrical features. The halogenated corroles reported herein exhibit significantly improved antiviral activity over their non-halogenated counterparts and over nitro-corrole analogs previously reported. Full activity of thirteen A3-corroles is achieved with four fluorine atoms present on the meso-phenyl ring reaching a selectivity index above 300. The maximum activity is achieved for A2B-corroles with selectivity indexes above 400. We thus demonstrate that the fluorocorrole is a highly potent platform to synthesize a new generation of anti hCMV molecules.

Synthesis and the Effect of Anions on the Spectroscopy and Electrochemistry of Mono(dimethyl sulfoxide)-Ligated Cobalt Corroles.

A new series of cobalt A3-triarylcorroles were synthesized and the compounds examined as to their electrochemical and spectroscopic properties in CH2Cl2 or dimethyl sulfoxide (DMSO) containing 10 different anions added to the solution in the form of tetrabutylammonium salts. The investigated anions were PF6-, BF4-, HSO4-, ClO4-, Br-, I-, Cl-, OAc-, F-, OTs-, and CN-, all but three of which were found to facilitate reduction of the cobalt corrole in dilute CH2Cl2 solutions, as determined by a combination of UV-vis spectroscopy and spectroelectrochemistry. The synthesized corroles are represented as (Ar)3CorCo(DMSO), where Ar is a meso-phenyl group containing one of 10 different electron-donating or -withdrawing substituents. The axial DMSO ligand was found to dissociate in dilute (10-5 M) CH2Cl2 solutions, but this was not the case at the higher electrochemical concentration of 10-3 M, where the investigated corroles exhibit a rich redox reactivity, undergoing up to five reversible one-electron-transfer reactions under the different solution conditions. The reversible half-wave potentials for generation of the singly oxidized corroles varied by over 1.0 V with a change in the electron-donating or -withdrawing meso-phenyl substituents and type of anion added to the solution, ranging from E1/2 = 0.83 V in one extreme to -0.42 V in the other. Much smaller shifts in the potentials (on the order of ∼210 mV) were observed for the reversible first reduction as a function of changes of the anion and/or corrole substituents, with the only exception being in the case of CN-, where the E1/2 values in CH2Cl2 ranged from +0.08 V in solutions containing 0.1 M TBAClO4 to >-1.8 V upon the addition of CN-.

Porous organic polymers based on cobalt corroles for carbon monoxide binding.

Porous organic polymers (POPs), known for their high surface area and porosity, were prepared starting from tetraphenyl tetrahedral-shaped building blocks and corrole macrocyclic linkers either as free bases or cobalt complexes. This synthetic method allowed us to construct new porous frameworks with high carbon monoxide adsorption properties. Two synthetic strategies were developed for incorporating cobalt corroles into the porous matrix. The first method is based on the copper-free Sonogashira cross-coupling reaction between a free base diodo-corrole with a tetrahedral shaped derivative followed by cobalt complexation of the resulting material, leading to POP-CorCo-1. The second strategy consists of preparing POP-CorCo-2 by directly using in the coupling reaction the metalated cobalt corrole temporarily protected by two ammine ligands at the axial position. The design principles as well as the relationship between the structure and the selective CO adsorption performance are presented. The adsorption capacities and selectivities of CO were calculated from a multisite Langmuir isotherm model and using IAST theory. Spectroscopic studies (NMR, FTIR, UV-visible), kinetic sorption measurements and microscopic analyses made possible to provide a fairly complete description of the structure of the POPs, their porosity and the nature of solid-gas interactions. The POPs prepared by both methods show a high permanent porosity and outstanding CO sorption properties with a high selectivity over N2, O2 and CO2, up to 15 700, 4000 and 1800, respectively. The two POP-CorCo therefore offer confined molecular spaces for ascertaining a high accessibility of the metallocorrole active sites for gas binding on the cobalt atom, thus featuring high potential for applications in selective capture or sensing of CO versus N2, O2 and CO2.

Ligand Noninnocence in Cobalt Dipyrrin-Bisphenols: Spectroscopic, Electrochemical, and Theoretical Insights Indicating an Emerging Analogy with Corroles.

Three cobalt dipyrrin-bisphenol (DPPCo) complexes with different meso-aryl groups (pentafluorophenyl, phenyl, and mesityl) were synthesized and characterized based on their electrochemistry and spectroscopic properties in nonaqueous media. Each DPPCo undergoes multiple oxidations and reductions with the potentials, reversibility, and number of processes depending on the specific solution conditions, the specific macrocyclic substituents, and the type and number of axially coordinated ligands on the central cobalt ion. Theoretical calculations of the compounds with different coordination numbers are given in the current study in order to elucidate the cobalt-ion oxidation state and the innocence or noninnocence of the macrocyclic ligand as a function of the changes in the solvent properties and degree of axial coordination. Electron paramagnetic resonance spectra of the compounds are obtained to experimentally assess the electron spin state. An X-ray structure of the six-coordinate complex is also presented. The investigated chemical properties of DPPCo compounds under different solution conditions are compared to those of cobalt corroles, where the macrocycle and metal ion also possess formal 3- and 3+ oxidation states in their air-stable forms.

Gold dipyrrin-bisphenolates: a combined experimental and DFT study of metal-ligand interactions.

Given that noninnocent and metalloradical-type electronic structures are ubiquitous among dipyrrin-bisphenolate (DPP) complexes, we synthesized the gold(iii) derivatives as potentially innocent paradigms against which the properties of other metallo-DPP derivatives can be evaluated. Electronic absorption spectra, electrochemical studies, a single-crystal X-ray structure, and DFT calculations all suggest that the ground states of the new complexes indeed correspond to an innocent AuIII-DPP3-, paralleling a similar description noted for Au corroles. Interestingly, while DFT calculations indicate purely ligand-centered oxidations, reduction of AuDPP is predicted to occur across both the metal and the ligand.