Corrole Derivatives Research Articles

The photophysical, photobiological, and light-up calf-thymus-DNA sensor activity of Pd(II) and Pt(II) polypyridyl derivatives coordinated to vinyl-pyridyl corroles

A series of mono-cationic corroles containing bipyridyl derivatives coordinated with Pd(II) and Pt(II) polypyridyl complexes is reported here. These corroles were characterized by microanalysis, UV–Vis absorption, steady-state and time-resolved fluorescence emission, theoretical DFT calculations, and electrochemical techniques. Photobiological parameters, such as photostability and ROS production, were also assessed. Spectroscopic and viscometry studies, along with molecular docking calculations, revealed each corrole derivative's ability to interact with the minor grooves of calf-thymus DNA. Additionally, the potential of these derivatives to act as emissive optical sensors for CT-DNA was evaluated.

Red-emission, photobiological properties and antimicrobial photodynamic assays using mono-substituted corroles contain carboxylic acid and ester units

The mono-substituted corrole derivatives COOH-Cor and COOMe-Cor were obtained by Gryko methodology and characterized by microanaysis. In addition, we investigated experimental photophysical properties (absorption, emission by steady-state and time-resolved fluorescence) in some solvents and TDDFT calculations. Photobiological parameters such as aggregation, photostability and reactive oxygen species generation (ROS) was conducted. In addition, we also evaluated the preliminary antimicrobial photodynamic assays (aPDT) between studied corroles and bacteria strains, by white-light conditions.

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.

The photophysical, photobiological, and DNA/HSA-binding properties of corroles containing carbazole and phenothiazine moieties

This study characterized four corrole derivatives, namely Cbz-Cor, MetCbz-Cor, PTz-Cor, and PTzEt-Cor, examining their photophysical, electrochemical, photobiological, and biomolecule-binding properties. Experimental photophysical data of absorption and emission elements correlated with a theoretical analysis obtained through time-dependent density functional theory (TD-DFT). As for the photophysical properties, we observed lower fluorescence quantum yields and discernible differences between the excited and ground states, as indicated by Stokes shift values. Natural Transition Orbit (NTO) plots presented high occupied molecular orbital - low unoccupied molecular orbital (HOMO-LUMO) densities around the tetrapyrrolic macrocycle in all examples. Our findings demonstrate that corroles maintain stability in solution and offer photostability (<20 %), predominantly in DMSO(5 %)/Tris-HCl (pH 7.4) buffer solution. Furthermore, the singlet oxygen (1O2) quantum yield and log POW values underscore their potential application in photoinactivation approaches, as these corroles serve as effective ROS generators with more lipophilic features. We also evaluated their biomolecular binding capacity towards salmon sperm DNA and human serum albumin using spectroscopic techniques and molecular docking analysis for sustenance. Concerning biomolecule interaction profiles, the corrole derivatives showed a propensity for interacting in the minor grooves of the double helix DNA due to secondary forces, which were more pronounced in site III of the human serum protein.

Tailoring intersystem crossing in phosphorus corroles through axial chalcogenation: a detailed theoretical study.

Intersystem crossing (ISC) of visible-light absorbing metal-free corrole macrocycles can be greatly tuned by means of suitable chemical functionalization. Axially chalcogenated phosphorus corrole derivatives (XPCs; X = O, S, Se) are expected to show large spin-orbit coupling (SOC) via the heavy-atom effect and therefore a much improved ISC. Excited-state deactivation of XPCs including PC is studied using time-dependent optimally tuned range-separated hybrid functionals combined with a polarizable continuum model with toluene as a dielectric medium to account for polar solvent effects. PC and all XPCs are dynamically stable and also show favourable thermodynamic formation feasibility as confirmed by Gibbs free energy analysis. In spite of the relatively smaller contribution of P and X to the frontier molecular orbitals compared to the tetrapyrrolic ring, SOC is considerably improved due to the heavy-atom effect. While PC shows a one-order larger ISC rate of ∼107 s-1 than fluorescence, competitive fluorescence and ISC rates of ∼107 s-1 are found for OPC. In contrast, both SPC and SePC exhibit significantly larger ISC rates of ∼109 s-1 and ∼1013 s-1, respectively, with much smaller fluorescence rates of ∼107 s-1. Importantly, the first report of anti-Kasha's emission in metal-free corroles is predicted for OPC with a radiative rate of ∼109 s-1. Furthermore, calculated phosphorescence and ISC rates from the near-degenerate lowest excited triplets to the ground-state suggest millisecond to microsecond triplet lifetimes, signalling towards long-lived excited triplet formation. Overall, all three XPCs including PC could act as triplet photosensitizers and especially both SPC and SePC are predicted to be the highly efficient ones.

Panchromatic and Perturbed Absorption Spectral Features and Multiredox Properties of Dicyanovinyl- and Dicyanobutadienyl-Appended Cobalt Corroles.

Four new β-functionalized π-extended cobalt corroles with one and two dicyanovinyl (DCV) or dicyanobutadienyl (DCBD) moieties at the 3- and 3,17-positions have been synthesized and characterized by various spectroscopic techniques. Interestingly, the synthesized DCV- and DCBD-appended cobalt corroles displayed panchromatic and near-infrared absorption in the range 300-1100 nm in CH2Cl2 and pyridine solvents. (MN)2-(Cor)Co and A2MN2-(Cor)Co exhibited 8-9 times enhancement in the molar absorptivity of the Q band compared to the parent corrole ((Cor)Co). The unique absorption spectral features of these β-functionalized cobalt corroles are splitting, broadening, and red-shifting in the Soret and Q bands. One DCV unit brings a 30-46 nm red shift, whereas one DCBD unit brings a 40-75 nm red shift in the Q band compared to the corresponding precursors. This is rare that the intensity of the longest Q band is greater than or equal to the Soret-like bands. These corrole derivatives exhibit UV-vis spectral features similar to those of chlorophyll a. A 220 mV positive shift per DCV group and 160 mV positive shift per DCBD group were observed in the first oxidation potentials compared to (Cor)Co in the desired direction for the utility of these cobalt complexes in electrocatalysis. DFT studies revealed that HOMO and LUMO were stabilized after appending DCV and DCBD groups on the corrole macrocycle and exhibited a "push-pull" behavior leading to promising material applications in nonlinear optics (NLO) and catalysis.

A novel colorimetric NIR fluorescent probe for turn-on detection and imaging of hydrogen sulfide

A near-infrared emission fluorescent turn-on probe FC-DNBS for H2S detection was synthesized based on assembling hydroxyphenyl substituted corrole derivative with 2,4-dinitrobenzenesulfonyl moiety. FC-DNBS could recognize H2S through thiolysis reaction triggered by HS- to liberate 5,15-di(4-fluorophenyl)-10-(4-hydroxylphenyl)-corrole (FC-OH), which produced a strong red fluorescent signal (652 nm). The sensing mechanism was checked by 1H NMR, MS and the DFT calculations. FC-DNBS displayed ultra-fast response (18 s), high selectivity and sensitivity (LOD: 48 nM), large Stokes shift (228 nm), and “naked eye” visualization for tracing H2S. Thanks to these unique features, FC-DNBS has been successfully applied for NIR fluorescence for detection and imaging of H2S in natural waters, red wines, living cells and zebrafish, demonstrating its value of practical applications in food samples and biological systems.

Photodynamic antitumor activity of dihydroxyl A2B triaryl corrole and its gallium(III) and phosphorus(V) complexes

Two new dihydroxyl A2B triaryl corroles 10-(2,4-dihydroxyphenyl)-5,15-bis(pentafluorophenyl)corrole (1) and 10-(3,4-dihydroxyphenyl)-5,15-bis(pentafluorophenyl)corrole (2) and their gallium(III) and phosphorus(V) complexes (1-Ga, 2-Ga, 1-P and 2-P) were synthesized and investigated as photodynamic antitumor agents. All synthesized corrole derivatives could generate singlet oxygen smoothly under illumination at 620–625 nm and showed remarkable in vitro photodynamic antitumor activity. Excited, phosphorus(V) corrole 1-P even exhibited better phototoxicity towards A549 and MDA-MB-231 tumor cell line (IC50, 0.08 and 0.12 µM) than clinical drug Foscan® (IC50, 0.27 µM). The laser confocal microscopy results showed that the cellular absorbed 1-P was located in the cytoplasm. Under illumination, intracellular reactive oxygen species (ROS) could be detected, which would triger the destruction of the mitochondrial membrane potential and finally lead to apoptosis. Furthermore, the 1-P photodynamic treatment would cause the cancer cells arrested at sub-G1 stage.

Fluorescence detection of hydrazine in an aqueous environment by a corrole derivative.

Broadly, the industrial applications of hydrazine cause environmental pollution and damage to living organisms because of the high toxicity of hydrazine. Therefore, monitoring hydrazine in the environmental system is of great significance to human health. Here, a new fluorescent probe PC-N2 H4 based on corrole dye was developed for the detection of hydrazine that had excellent specificity, low limit of detection (LOD: 88 nM), and a wide pH range (6-12). Upon addition of hydrazine into the probe solution, the strong red fluorescence was 'turned on' centred at 653 nm with a 127-fold fluorescence intensity enhancement. The detection mechanism was proved using ESI-MS, 1 H NMR, and density functional theoretical calculations. Importantly, the probe was utilized to fabricate a ready-to-use test strip to realize the visual inspection of hydrazine. Furthermore, PC-N2 H4 was successfully applied for practical detection of hydrazine in water samples with satisfactory recoveries ranging from 96.2% to 105.0%, and indicating that the designed PC-N2 H4 is highly promising for hydrazine detection in an aqueous environment. Considering the diverse toxicological functions of hydrazine, PC-N2 H4 was also successfully used to image exogenous hydrazine in HeLa cells and zebrafish.

Photophysical, photobiological, and biomolecule-binding properties of new tri-cationic meso-tri(2-thienyl)corroles with Pt(II) and Pd(II) polypyridyl derivatives

We report the synthesis and characterization of new tri-cationic corrole derivatives, containing Pt(II) or Pd(II) complexes attached at the peripheral position of thienyl moieties. Corrole derivatives were characterized through microanalysis, electrochemical, spectrometry and spectroscopy analysis. Singlet and triplet excited-states are investigated by photophysical/theoretical calculation methods and photobiological parameters were also evaluated spectroscopic techniques (UV–Vis and EPR). Also, the binding capacity of each corrole derivative with nucleic acids (DNA) and human serum albumin (HSA) was determined by UV–Vis, steady-state, and time-resolved fluorescence spectroscopy, combined with molecular docking analysis. Moreover, the new corroles containing peripheral complexes improve their interactions with biomacromolecules, generate reactive oxygen species under light source irradiation studied and has potential for application in photodynamic therapeutic processes.

Tuning the Molecular Structure of Corroles to Enhance the Antibacterial Photosensitizing Activity.

The increase in the antibiotic resistance of bacteria is a serious threat to public health. Photodynamic inactivation (PDI) of micro-organisms is a reliable antimicrobial therapy to treat a broad spectrum of complex infections. The development of new photosensitizers with suitable properties is a key factor to consider in the optimization of this therapy. In this sense, four corroles were designed to study how the number of cationic centers can influence the efficacy of antibacterial photodynamic treatments. First, 5,10,15-Tris(pentafluorophenyl)corrole (Co) and 5,15-bis(pentafluorophenyl)-10-(4-(trifluoromethyl)phenyl)corrole (Co-CF3) were synthesized, and then derivatized by nucleophilic aromatic substitution with 2-dimethylaminoethanol and 2-(dimethylamino)ethylamine, obtaining corroles Co-3NMe2 and Co-CF3-2NMe2, respectively. The straightforward synthetic strategy gave rise to macrocycles with different numbers of tertiary amines that can acquire positive charges in an aqueous medium by protonation at physiological pH. Spectroscopic and photodynamic studies demonstrated that their properties as chromophores and photosensitizers were unaffected, regardless of the substituent groups on the periphery. All tetrapyrrolic macrocycles were able to produce reactive oxygen species (ROS) by both photodynamic mechanisms. Uptake experiments, the level of ROS produced in vitro, and PDI treatments mediated by these compounds were assessed against clinical strains: methicillin-resistant Staphylococcus aureus and Klebsiella pneumoniae. In vitro experiments indicated that the peripheral substitution significantly affected the uptake of the photosensitizers by microbes and, consequently, the photoinactivation performance. Co-3NMe2 was the most effective in killing both Gram-positive and Gram-negative bacteria (inactivation > 99.99%). This work lays the foundations for the development of new corrole derivatives having pH-activable cationic groups and with plausible applications as effective broad-spectrum antimicrobial photosensitizers.

The role of solvents and concentrations in the properties of oxime bearing A2B corroles.

A comprehensive study on the electronic spectral, photophysical and acid-base properties of phenyl- and methyl-oxime corrole derivatives and of triphenylcorrole (model corrole) has been performed, aiming to shed light on the existing species in the ground and excited states. Solvents and corrole concentration are found to govern the properties of the studied compounds and are determinants of their applicability in in vivo studies. In THF, the neutral corrole has two tautomeric forms (T1 and T2). In DMSO, the deprotonated form shows a characteristic long-wavelength Q band slightly shifted to blue when compared with the T1 tautomer and a higher fluorescence quantum yield. In ACN, with the increase of the corrole concentration formation of an aggregate due to homoconjugation (with dimer characteristics) is observed, and pioneeringly reported using UV-Vis and fluorescence studies and confirmed by carrying out titrations with TFA. The effect of the oxime group on the pK values of a corrole is found to influence the formation of a homoconjugate, namely by precluding its formation (at higher concentrations) when compared with the model corrole. TDDFT electronic quantum calculations support the experimental observations, namely the existence of tautomers and deprotonated species, with their respective electronic spectral features, further allowed proposing a structure for the homoconjugate complex in ACN. The characteristics of the oxime-corroles, namely a pK of ∼ 5, absorption and emission at ca. 650 nm and solvent dependent properties, make them good candidates for their use in biological systems either as probes, sensors, or as new sensitizers for photodynamic therapy.

Reaction of Corroles with Sarcosine and Paraformaldehyde: A New Facet of Corrole Chemistry.

Details on the unexpected formation of two new (dimethylamino)methyl corrole isomers from the reaction of 5,10,15-tris(pentafluorophenyl)corrolatogallium(III) with sarcosine and paraformaldehyde are presented. Semi-empirical calculations on possible mechanism pathways seem to indicate that the new compounds are probably formed through a Mannich-type reaction. The extension of the protocol to the free-base 5,10,15-tris(pentafluorophenyl)corrole afforded an unexpected new seven-membered ring corrole derivative, confirming the peculiar behavior of corroles towards known reactions when compared to the well-behaved porphyrin counterparts.

A near-infrared fluorescent probe based on corrole derivative with large Stokes shift for detection of hydrogen sulfide in water and living cells

A distinct near-infrared (NIR) fluorescent probe (COR-DNBS), based on corrole derivative, was designed and synthesized for detection of hydrogen sulfide (H2S) by the photoinduced electron transfer (PET) mechanism. Probe COR-DNBS was constructed by 5,15-di(4-chlorophenyl)-10-(4-hydroxylphenyl)-corrole (COR-OH) as fluorophore and 2,4-dinitrobenzenesulfonyl ether (DNBS) as recognition site. The chemical structure of COR-DNBS was fully characterized by 1H NMR, 13C NMR, EA, IR and mass spectrometry. COR-DNBS showed a high selectivity and an excellent sensitivity to H2S with a detection limit of 28 nM together with a fast response (46 s). Importantly, it also exhibited a large Stokes shift (231 nm) and red emission (656 nm), which is highly desirable for bioimaging applications. The sensing mechanism was proved to be H2S triggered thiolysis reaction by 1H NMR, HRMS and the DFT calculations. In the present work, successful detection and bioimaging of H2S in water and living cells was achieved. Moreover, COR-DNBS could be used as a paper test strip for monitoring and screening of H2S in environment.

Structure-sensitive marker bands of metallocorroles: A resonance Raman study of manganese and gold corrole derivatives

Soret-excited resonance Raman spectra (λex 413.1 nm) were acquired for manganese(III) and gold(III) tris(pentafluorophenyl)corrole, each as four different isotopomeric samples: natural abundance, fully pyrrole-15N-substituted, fully meso-13C-substituted, and fully pyrrole-15N-meso-13C-substituted. The spectra were modeled with density functional theory-based vibrational analyses, which in general did an excellent job of reproducing both the absolute frequencies and isotope shifts. The results led to the assignment and visualization of approximately 10 prominent Raman bands. A key finding was that the bands could be categorized into two broad classes: Class A, exhibiting large 15N isotope shifts, assignable to vibrations with predominant Cα-N character, and Class B, exhibiting large meso-13C isotope shifts, assignable to vibrations with predominant Cα-Cmeso character. Preliminary evidence suggests that the class A bands may serve as core size markers, while class B bands may correlate with the innocence or otherwise of the corrole macrocycle.

Corroles at work: a small macrocycle for great applications.

Corrole chemistry has witnessed an impressive boost in studies in the last 20 years, thanks to the possibility of preparing corrole derivatives by simple synthetic procedures. The investigation of a large number of corroles has highlighted some peculiar characteristics of these macrocycles, having features different from those of the parent porphyrins. With this progress in the elucidation of corrole properties, attention has been focused on the potential for the exploitation of corrole derivatives in different important application fields. In some areas, the potential of corroles has been studied in certain detail, for example, the use of corrole metal complexes as electrocatalysts for energy conversion. In some other areas, the field is still in its infancy, such as in the exploitation of corroles in solar cells. Herein, we report an overview of the different applications of corroles, focusing on the studies reported in the last five years.

Comparing Isoelectronic, Quadruple-Bonded Metalloporphyrin and Metallocorrole Dimers: Scalar-Relativistic DFT Calculations Predict a >1 eV Range for Ionization Potential and Electron Affinity.

A scalar-relativistic DFT study of isoelectronic, quadruple-bonded Group 6 metalloporphyrins (M = Mo, W) and Group 7 metallocorroles (M = Tc, Re) has uncovered dramatic differences in ionization potential (IP) and electron affinity (EA) among the compounds. Thus, both the IPs and EAs of the corrole derivatives are 1 eV or more higher than those of the porphyrin derivatives. These differences largely reflect the much lower orbital energies of the δ- and δ*-orbitals of the corrole dimers relative to those of the porphyrin dimers, which in turn reflect the higher (+III as opposed to +II) oxidation states of the metals in the former compounds. Significant differences have also been determined between Mo and W porphyrin dimers and between Tc and Re corrole dimers. These differences are thought to largely reflect greater relativistic destabilization of the 5d orbitals of W and Re relative to the 4d orbitals of Mo and Tc. The calculated differences in IP and EA should translate to major differences in electrochemical redox potentials-a prediction that in our opinion is well worth confirming.

Unveiling the photophysical, biomolecule binding and photo-oxidative capacity of novel Ru(II)-polypyridyl corroles: A multipronged approach

Two fluorinated corrole derivatives, namely H3MebpyCor and RuMebpyCor, were synthesized and characterized in terms of their photophysical, electrochemical, and photooxidation behavior. Their biomolecular binding capacity toward Human Serum Albumin (HSA) and calf thymus DNA (CT-DNA) was also evaluated. The experimental data were correlated with theoretical analysis via Time Dependent Density Functional Theory (TDDFT) and Molecular Docking calculations. We found an extremely low fluorescence quantum yield for both corroles dissolved in acetonitrile (CH3CN) and dimethyl sulfoxide (DMSO), which suggests a relaxation pathway through nonradiative processes, such as internal conversion. However, the internal conversion channel in RuMebpyCor competes with the energy transfer to the Ru(II) moiety, placing triplet state formation as a second mechanism of relaxation for this structure. Both corroles showed no aggregation and good photostability. The singlet oxygen (1O2) quantum yield (ΦΔ) values also highlight their potential application in photoinactivation approaches. Theoretical analysis suggests that the introduction of Ru(II) ion coordinated in the bipyridyl unit significantly alters the optically induced electronic transitions, and that the solvents play an important role in defining the optical spectra of the two corroles. Additionally, they interact spontaneously and moderate to strong via ground-state association (static process) with HSA and CT-DNA. However, for the HSA binding assays the dynamic fluorescence quenching mechanism can also occur at high corrole concentrations. Finally, in silico calculations suggest that the main binding region into CT-DNA is the minor groove, while subdomain IIA (site I) is the main binding region for HSA:H3MebpyCor (experimental proportion 1:1) and both subdomains IIA and IB (sites I and III, respectively) for HSA:RuMebpyCor (experimental proportion 1:2).

Functionalized Corroles for Sensor Applications

Corrole continues to attract the interest of different research groups, since this macrocycle shows peculiar and intriguing characteristics, which open its application in different fields.In the last few years, we have been interested to exploit corrole derivatives as receptors in chemical sensors, because the peculiar coordination chemistry of this contracted macrocycle can allow the preparation of optimized cross sensitive sensor arrays.For this reason, the functionalization of the corrole is a fundamental step for the optimization of the macrocycle features for the target application.We have been interested in the introduction at the peripheral positions of the corrole ring of different substituents, because they can allow the preparation of hybrid materials. These hybrid materials have been successfully exploited to develop chemical sensors.The characterization of these species, together the applications of the functionalized corroles will be presented and discussed.

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.