Porphyrin Analogues Research Articles

The Breaking and Mending of meso-Tetraarylporphyrins: Transmuting the Pyrrolic Building Blocks.

Naturally occurring porphyrins and hydroporphyrins vary with respect to their ring substituents and oxidation states, but their tetrapyrrolic frameworks remain fully preserved across all kingdoms of life; there are no naturally occurring porphyrin-like macrocycles known that contain nonpyrrolic building blocks. However, the study of porphyrin analogues in which one or two pyrroles were replaced with nonpyrrolic building blocks might shed light on the correlation between structural modulation and ground and excited state optical properties of the "pigments of life", unlocking their mechanisms of function. Also, porphyrinoids with strong absorbance and emission spectra in the NIR are sought after in technical (e.g., light-harvesting) and biomedical (e.g., imaging and photochemotherapy) applications. These porphyrin analogues, the so-called pyrrole-modified porphyrins (PMPs), are synthetically accessible using total syntheses. Alternatively-and most handily-they can also be formed by conversion of synthetic porphyrins. Guided by older reports of the fortuitous modifications of porphyrins into PMPs, our research program generalized the so-dubbed "Breaking and Mending of Porphyrins" approach toward PMPs. This method to convert a pyrrole in meso-tetraarylporphyrins to a nonpyrrolic building block with high precision relies on a number of distinct steps. Step 1: The porphyrin is functionalized in a way that activates one or two peripheral double bonds toward breakage; in all cases surveyed here, this step is an osmium tetroxide-mediated dihydroxylation to generate dihydroxychlorin and tetrahydroxybacteriochlorins. Step 2: The activated, dihydroxylated β,β'-bond is "broken". Step 3: The functional groups resulting from the ring-cleavage reactions are utilized in subsequent "mending" steps to form the PMPs, that themselves may be subject to further modifications, Step 4. Thus, PMPs in which a pyrrole was degraded to an imine linkage, contracted to a four-membered ring, or expanded by oxygen, sulfur, carbon, or nitrogen atoms to form six-membered building blocks have become accessible. This approach also allowed the replacement of a single β-carbon atom by a nitrogen or oxygen atom. Depending on the ring size, conformation, conformational flexibility, the oxidation state of the pyrrole replacements, or the presence of substituents that π-extend the chromophores, the PMPs possess porphyrin- or hydroporphyrin-like optical spectra, or they show altogether unique electronic properties. Some PMP classes allow the fine-tuning of their absorption range; others exhibit panchromatic absorption spectra from the UV to the NIR. Several PMPs take up persistent chiral helimeric conformations that could be resolved. This Account summarizes the scopes of the "Breaking and Mending" methodology with a special focus on laying out the structural diversity of PMPs accessible from meso-tetraarylporphyrins and highlighting their optical properties, with the aim of encouraging their further study and application.

Out of the Blue! Azuliporphyrins and Related Carbaporphyrinoid Systems.

First reported in 1997, azuliporphyrins have proven to be a truly remarkable family of porphyrin analogues. In this system, although the porphyrin framework is retained, one of the pyrrolic moieties has been replaced by an azulene unit. Azulene favors electrophilic substitution at the 1,3-positions, which are structurally analogous to the α-positions in pyrrole, and this property facilitates the construction of azulene-containing porphyrinoid systems. Azuliporphyrins were first prepared from tripyrranes and 1,3-azulenedicarbaldehyde using a "3 + 1" variant on the MacDonald reaction. Subsequently, azulenes were shown to react with acetoxymethylpyrroles under acidic conditions to generate azulitripyrranes that could be utilized in a back-to-front "3 + 1" methodology to form azuliporphyrins and related heteroporphyrinoids. In addition, the favorability of azulenes toward 1,3-substitution was applied to one-pot syntheses of tetraarylazuliporphyrins and calix[4]azulenes. Azuliporphyrins have significant diatropic character that is greatly enhanced upon protonation. They have been shown to form organometallic complexes with Ni(II), Pd(II), Pt(II), Ir(III), Rh(III), and Ru(II) and undergo selective oxidations at the internal carbon with copper(II) or silver(I) salts to afford 21-oxyazuliporphyrins. In addition, oxidative ring contractions readily occur under basic conditions in the presence of peroxides to give benzocarbaporphyrins, and this reactivity provides access to tetraarylbenzocarbaporphyrins and their organometallic derivatives. A diazulenylmethane dialdehyde has been shown to react with dipyrrylmethanes in the presence of HCl or HBr to give diazuliporphyrins that were isolated in a monoprotonated form, and metalation with palladium(II) acetate afforded a stable zwitterionic palladium(II) complex. Equally intriguing dicarbaporphyrinoids incorporating indene and azulene rings have been reported, and these systems exhibit significant aromatic character. Recent studies have demonstrated that calixazulenes form supramolecular complexes with quaternary ammonium salts and afford a 1:1 complex with C60. In addition, conjugated structures have been prepared from calixazulenes that are structurally related to quatyrin, the theoretically important hydrocarbon analogue of the porphyrins. Examples of expanded azuliporphyrinoids have also been described. These azulene-containing porphyrinoids exhibit unique and complex reactivity that compares favorably with better studied porphyrin analogue systems such as the N-confused porphyrins, and azuliporphyrin derivatives show promise in the development of new catalytic systems.

New carbazole appended subporphyrin displaying intramolecular charge transfer and solid state fluorescence

A new subporphyrin namely, hydroxo-5,10,15-tri([Formula: see text]-propyl-3-carbazolyl)subporphyri natoboron(III) 6 has been synthesized via the reported litreture procedure by the condensation of pyridine-tri-[Formula: see text]-pyrrolylborane with 9-propyl-9H-carbazole-3-carbaldehyde. Its porphyrin analog [Formula: see text]. 5,10,15,20-tetra([Formula: see text]-propyl-3-carbazolyl)porphyrin has also been isolated from the reaction mixture, formed due to scrambling process and complexed with Zn(II). Photophysical properties of both subporphyrin and Zn(II)porphyrin have been studied in detail to confirm the intramolecular charge transfer process in subporphyrin analog. In addition, the ring contracted congener 6 also displays solid state fluorescence.

Modulation of singlet oxygen generation and amphiphilic properties of trihydroxylated monohalogenated porphyrins

Two of the properties important for photodynamic therapy applications are systematically investigated on a trihydroxylated monohalogenated porphyrin core. Singlet oxygen generation can be increased thanks to the heavy atom effect, frequently provided by the introduction of halogen atoms on the photosensitizer. We compare the effect of the presence of the four halogen atoms with the analogous halogen-free porphyrin. Cell uptake is crucial as well for successful photodynamic outcome and is directly related to the amphiphilicity of the molecule. The five derivatives bearing H, F, Cl, Br or I atoms are compared in this regard. The presence of iodine atom induces a sharp difference in singlet oxygen generation compared to all the other derivatives investigated, but increases its lipophilicity, still in the limits suitable for biomedical applications.

Effects of Immersion Solvent on Photovoltaic and Photophysical Properties of Porphyrin-Sensitized Solar Cells.

Memory effects in self-assembled monolayers (SAMs) of zinc porphyrin carboxylic acid on TiO2 electrodes have been demonstrated for the first time by evaluating the photovoltaic and electron transfer properties of porphyrin-sensitized solar cells prepared by using different immersion solvents sequentially. The structure of the SAM of the porphyrin on the TiO2 was maintained even after treating the porphyrin monolayer with different neat immersion solvents (memory effect), whereas it was altered by treatment with solutions containing different porphyrins (inverse memory effect). Infrared spectroscopy shows that the porphyrins in the SAM on the TiO2 could be exchanged with the same or analogous porphyrin, leading to a change in the structure of the porphyrin SAM. The memory and inverse memory effects are well correlated with a change in porphyrin geometry, mainly the tilt angle of the porphyrin along the long molecular axis from the surface normal on the TiO2, as well as with kinetics of electron transfer between the porphyrin and TiO2. Such a new structure-function relationship for DSSCs will be very useful for the rational design and optimization of photoelectrochemical and photovoltaic properties of molecular assemblies on semiconductor surfaces.

Static polarization of the supramolecular dyads of fullerene C60 with porphyrin derivatives

The nonlinear optical properties of four supramolecular dyads consisting of fullerene C 60 non-covalently bonded to porphyrin, porphyrazine, tetrabenzoporphyrin and phthalocyanine were investigated by calculating their electronic polarizability and first- and second-order hyperpolarizabilities using the finite field method and the density functional theory with the Grimme dispersion correction. Large first- and second-order hyperpolarizabilities result in nonlinear dependence of the polarization of dyads on the strength of external electric field. The increase in the size of the π-conjugated electron system of the porphyrin analogs leads to the increase of the polarizability and first- and second-order hyperpolarizabilities of the dyads. The absence of the covalent bonds between the components of the dyads prevents the field-induced electron transfer from porphyrin analogs to fullerene. The main reason for the nonlinear behavior of the polarization of dyads is the mutual polarization of fullerene and porphyrin analogs amplified by the external electric field.

Meso-Phenyl-triazole bridged porphyrin-coumarin dyads: Synthesis, characterization and photophysical properties

Novel zinc (II) meso-phenyl-triazole bridged porphyrin-coumarin dyads have been synthesized in good to excellent yields through copper (I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction of zinc (II) 5-(4-azidophenyl)-10,15,20-triphenylporphyrin with diverse coumarinoalkynes in dimethylformamide containing ascorbic acid at 80 °C. These compounds successfully underwent demetallation in the presence of concentrated hydrochloric acid to afford the corresponding free-base porphyrins which on treatment with nickel acetate in chloroform-acetic acid mixture produced various nickel (II) meso-triazole bridged porphyrin-coumarin dyads in good yields. All the newly synthesized products were characterized on the basis of spectral data and elemental analyses. The preliminary photophysical results revealed a significant intramolecular energy transfer between porphyrin core and coumarin moiety in the case of zinc porphyrin analogues.

Out of the Blue! Azuliporphyrins and Related Azulene-Containing Porphyrinoids

Carbaporphyrinoids, porphyrin analogues that have one or more of the usual pyrrolic units replaced by carbocyclic rings, have been widely studied in recent years. These systems exhibit a wide range of properties and varying degrees of macrocyclic aromaticity. Azuliporphyrins have an azulene ring incorporated into the porphyrin framework and exhibit intermediary aromatic character. They were first prepared by reacting tripyrranes with 1,3-azulenedicarbaldehyde under acid-catalyzed conditions, although several alternative routes have been developed for preparing this intriguing carbaporphyrinoid system. Azuliporphyrins are easily protonated and this greatly enhances the diatropic properties for the macrocycle. Azuliporphyrins are also superior organometallic ligands and afford stable derivates with Ni(II), Pd(II), Pt(II), Ir(III) and Rh(III). Furthermore, tetraarylazuliporphyrins have been shown to undergo an oxidative metalation with copper(II) salts to generate a nonaromatic copper(II) complex. Treatment of azuliporphyrins with tert-butyl hydroperoxide under basic conditions triggers a ring contraction reaction to afford benzocarbaporphyrins. This appears to involve initial nucleophilic attack onto the seven-membered ring, followed by a Cope rearrangement and elimination of tert-butyl alcohol. These observations have led to investigations into related macrocyclic systems, including heteroazuliporphyrins with furan, thiophene or selenophene rings. In addition, an azulisapphyrin has also been reported. Dicarbaporphyrinoids with azulene-subunits have also been investigated. Azulene-containing fulvene dialdehydes have been shown to react with dipyrrylmethanes under acidic conditions to give 22-carbaporphyrins, and this system also shows intermediary aromatic character. In addition, a bis-azulenylmethane dialdehyde was shown to react with dipyrrylmethanes to give, following oxidation with DDQ, examples of diazuliporphyrins. This system was only stable in a protonated form but retained a degree of diatropic character. Reaction with palladium(II) acetate gave an unusual zwitterionic palladium(II) organometallic complex. These results demonstrate that azulene-containing porphyrinoids have unique properties and are superior precursors to organometallic derivatives.

New Push-Pull, Multicomponent Phthalocyanine-Based Photsensitizers for DSSCs

In the last few years, phthalocyanines (Pcs) have attracted strong interest in the field of dye-sensitized solar cells (DSSCs).1 A3B phthalocyanines such as TT40,2 functionalized with non-aggregating bulky substituents at three isoindole rings (i.e. A) and a highly directional carboxylic acid linker at the other isoindole (i.e. B), have reached photovoltaic power conversion efficiencies over 6% in hybrid devices with mesoporous TiO2. Although Pcs are more stable and strongly absorbing than porphyrin (Por) analogues, the latter have shown much more efficient as dyes for DSSCs, especially those with a “push-pull” substitution pattern, such as SM315.3 In the search for new hints for the rational molecular design and optimization routes, we aim to explore if this “push-pull “ pattern also applies to Pcs as a tool to achieve efficient sensitization of TiO2. Therefore, we have synthesized donor-π-acceptor Zn(II)Pcs such as 2, holding one electron-donor, aminophenyl–type unit and a carboxyethynyl moiety as acceptor and anchoring group, starting from ABAB Pc 1 recently reported by us.4 This Pc consist of two opposite isoindoles functionalized with bulky bis(trifluoromethyl)phenyl groups, which afford solubility to the molecule and hamper its aggregation, and two faced isoindoles containing iodine atoms, which can be used for further chemical transformation into the target donor-π-acceptor system 2. Additionally, we have undertaken the preparation of Zn(II)Por-Zn(II)Pc dyads 3, which absorb a broad part of the visible spectrum and show cascade-charge transfer capabilities, for the sensitization of TiO2. In these ensembles, the Zn(II)Por unit, functionalized with three arylamino moieties, features as the ultimate electron donor unit, and the carboxy Zn(II)Pc is responsible of the direct injection of electrons to the semiconducting film. 1 Martinez-Diaz, M. V.; de la Torre, G.; Torres, T. Chem. Commun. , 2010, 46, 7090. 2 Ragoussi, M.-E. ; Cid, J.-J. ; Yum, J.-H. ; de la Torre, G. ; Di Censo, D. ; Grätzel, M. ; Nazeeruddin, M. K.; Torres, T. Angew. Chem. Int. Ed. 2012, 51, 4375. 3 Mathew, S.; Yella, A.; Gao, P.; Humphry-Baker, R.; Curchod, B. F. E.; Ashari-Astani, N.; Tavernelli, I.; Rothlisberger, U.; Nazeeruddin, M. K. ; Grätzel, M.; Nature Chem. 2014, 6, 242. 4 Fazio, E. Jaramillo-Garcia, J.; de la Torre, G.; Torres, T. Org. Lett., 2014, 16, 4706. Figure 1

Chemistry of Novel Non-Aromatic, Meso-Alkylidenyl Carbaporphyrinoids

We developed new class of porphyrinoids and core-modified porphyrinoids that have not been well studied previously. So called, meso-alkylidenyl porphyrins and their congeners are rather recently developed porphyrinoid family that have shown several unique properties including tautomerization, unusual protonation selectivity and spectroscopic properties. We here report the chemistry of meso-diethyl malonylidene-(m-benzi)porphyrin and meso-diethyl malonylidene-(m-benzi)pentaphyrins such the reaction with in-situ generated azomethine ylides and redox reactions. This 1,3-dipolar cycloaddition reaction has well documented and become an important alternative to the synthesis of pi-extended porphyrin analogs. The versatility and synthetic utilities associated with these reactions is useful in the synthesis of pi-extended analogs of the meso-alkylidenyl porphyrinoids. Successive 1,3-dipolar cycloaddition reaction combined with oxidation could be good tool for the pi-extended porphyrin analogs bearing region-selectively fused pyrrole rings. The 1,3-dipolar cycloaddition of the corresponding Pd(II) complexes also resulted in bis-cyclized adducts which are resistant to DDQ oxidation. All adducts are liable to core N-methylation. The adducts exhibit large bathochromic shift of absorption.

Ring-Expanded Phthalocyanines Fused with Fluorene Skeleton for Light-Harvesting in the Near-IR Region

Organic photovoltaic devices (OPVs) based on thin films of organic semiconductors have been intensely investigated as a promising candidate for low-cost, lightweight, and scalable solar cells. While OPVs have achieved high conversion efficiencies, their organic semiconductors mainly absorb the light in visible range. To enhance their efficiency, the expansion of light-harvesting range is a key issue in this field. Phthalocyanines (Pcs) and their metal complexes (MPcs), synthetic porphyrin analogues, have been widely investigated as near-IR absorbing dyes because of their intense Q band (600-700 nm), high molar extinction coefficients (e > 100000 M-1 cm-1), and excellent thermal, chemical, and photolytic stabilities. The electronic structure and properties of MPcs can be tailored by modifying the macrocyclic ligands and changing the central metals [1]. We present here designed and synthesized novel ring-expanded zinc phthalocyanine (ZnFc , Figure1), in which four fluorene rings were fused with porphyrazine ring. Fusing fluorene rings with the porphyrazine rings lead to red-shifting the Q band and tailoring of the HOMO and LUMO energy levels as well as an expansion of p-system. We demonstrated the expansion of the light-harvesting area in BHJ solar cells based on poly(3-hexylthiophen) (P3HT) and 1-(3-methoxycalbonyl)-propyl-1-phenyl-(6,6)C61 (PCBM) by co-sensitizing with ZnFc. When the ZnFc decorated with eight alkyl chains was added to P3HT/PCBM BHJ solar cells, the solar cells showed a higher device efficiency with 16 % enhancement of JSC as compared with that of the reference P3HT/PCBM BHJ solar cells due to the expansion of light-harvesting range [2]. We also synthesized an asymmetrical fluorene-fused phthalocyanine (FcS1, Figure1), which containing three fused fluorene rings and one carboxylic acid. FcS1 indicated a potential for near-IR sensitizer in DSSCs. The absorption spectrum of FcS1 adsorbed onto a nano-crystalline TiO2 film suggested the formation of J-aggregation with tilted orientation of macrocyclic ligands. While the DSSC cells sensitized by FcS1 showed a modest efficiency of 3.2 % under simulated air mass 1.5 global sunlight, FcS1 could convert the red and near-IR light regions between 600 and 860 nm [3]. Reference [1] J. Mack, N. Kobayashi, Chem. Rev. 2011, 111, 281-321. [2] S. Yamamoto, M. Kimura, ACS Appl. Mater. Interfaces 2013, 5, 4367-4373. [3] S. Yamamoto, T. Ikeuchi, S. Mori, M. Kimura, Asian J. Org. Chem. 2014, 10, 1083-1088. Figure 1

Octaethyl-1,3-oxazinochlorin: A β-Octaethylchlorin Analogue Made by Pyrrole Expansion.

Treatment of the oxime of octaethyloxochlorin 4, available from octaethylporphyrin 3, under Beckmann conditions provided not the expected lactam, but octaethyl-1,3-oxazinochlorin 8, in which a pyrrole moiety of the parent oxochlorin was expanded by an oxygen atom to an 1,3-oxazinone moiety. Its mechanism of formation was demonstrated to occur along an "abnormal Beckmann" pathway, followed by intramolecular ring closure and hydrolysis. The work expands the methodologies known to convert octaethylporphyrin to pyrrole-modified porphyrin analogues.

Corroles-porphyrins: a teamwork for gas sensor arrays.

Porphyrins provide an excellent material for chemical sensors, and they have been used for sensing species both in air and solution. In the gas phase, the broad selectivity of porphyrins is largely dependant on molecular features, such as the metal ion complexed at the core of the aromatic ring and the peripheral substituents. Although these features have been largely exploited to design gas sensor arrays, so far, little attention has been devoted to modify the sensing properties of these macrocycles by variation of the molecular aromatic ring. In this paper, the gas sensing properties of a porphyrin analog, the corrole, are studied in comparison with those of the parent porphyrin. Results show that changes in the aromatic ring have important consequences on the sensitivity and selectivity of the sensors and that porphyrins and corroles can positively cooperate to enhance the performance of sensor arrays.

Allosteric regulation of the Plasmodium falciparum cysteine protease falcipain-2 by heme

During the erythrocytic cycle of Plasmodium falciparum malaria parasites break down host hemoglobin, resulting in the release of free heme (ferriprotoporphyrin IX). Heme is a generator of free radicals that cause oxidative stress, but it is detoxified by crystallization into hemozoin inside the food vacuole. We evaluated the interaction of heme and heme analogues with falcipain-2, a P. falciparum food vacuole cysteine protease that plays a key role in hemoglobin digestion. Heme bound to falcipain-2 with a 1:1 stoichiometry, and heme inhibited falcipain-2 activity against both human hemoglobin and chromogenic peptide substrates through a noncompetitive-like mechanism. A series of porphyrin analogues was screened for inhibition of falcipain-2, demonstrating a minor contribution of iron to heme–falcipain-2 interaction, and revealing dependence on both propionic and vinyl groups for inhibition of falcipain-2 by heme. Docking and molecular dynamics simulation unveiled a novel, inducible heme-binding moiety in falcipain-2 adjacent to the catalytic site. Kinetic data suggested that the noncompetitive-like inhibition was substrate inhibition induced by heme. Collectively these data suggest that binding of heme to falcipain-2 may limit the accumulation of free heme in the parasite food vacuole, providing a means of heme detoxification in addition to crystallization into hemozoin.

Theoretical studies on the absorption spectra and intramolecular charge transfer of push-pull zinc porphyrin dyes for dye-sensitized solar cells

The electronic structures, absorption spectra and intramolecular charge transfer properties of five push-pull zinc porphyrin analogs with different donor group and π bridge have been investigated by density functional theory(DFT) and TD(time-dependent)-DFT approach. The results show that the asymmetrical substituted diphenylamine group is favorable to the Q-band absorption of porphyrin dyes. The absence of the acetylenic bond in the π bridge part leads to the result that the B-band and the Q-band are blue-shifted and their absorption strength become weaker compared with that containing acetylenic bond, respectively. The introduction of the benzothiadiazole into the π bridge improves the intramolecular charge transfer.

Photophysical properties of β-substituted free-base corroles.

Corroles are an emergent class of fluorophores that are finding an application and reaction chemistry to rival their porphyrin analogues. Despite a growing interest in the synthesis, reactivity, and functionalization of these macrocycles, their excited-state chemistry remains undeveloped. A systematic study of the photophysical properties of β-substituted corroles was performed on a series of free-base β-brominated derivatives as well as a β-linked corrole dimer. The singlet and triplet electronic states of these compounds were examined with steady-state and time-resolved spectroscopic methods, which are complemented with density functional theory (DFT) and time-dependent DFT calculations to gain insight into the nature of the electronic structure. Selective bromination of a single molecular edge manifests in a splitting of the Soret band into x and y polarizations, which is a consequence of asymmetry of the molecular axes. A pronounced heavy atom effect is the primary determinant of the photophysical properties of these free-base corroles; bromination decreases the fluorescence quantum yield (from 15% to 0.47%) and lifetime (from 4 ns to 80 ps) by promoting enhanced intersystem crossing, as evidenced by a dramatic increase in knr with bromine substitution. The nonbrominated dimer exhibits absorption and emission features comparable to those of the tetrabrominated derivative, suggesting that oligomerization provides a means of red-shifting the spectral properties akin to bromination but without decreasing the fluorescence quantum yield.

Two-Photon Spectroscopy of the Q-Bands of meso-Tetraphenyl-Porphyrin and -Chlorin Framework Derivatives

The two-photon absorption and excitation spectra in the Q-band region (900–1360 nm) were measured for a number of porphyrinoids, including simple porphyrins (porphin, meso-tetraphenyl-porphyrin), chlorins (meso-tetraphenyl-2,3-dimethoxychlorin), and porphyrin and chlorin-like analogues (meso-tetraphenyl-porpholactone and meso-tetraphenyl-porpholactol, respectively). These molecules were chosen to provide a series of compounds that differed structurally only in “single points”. Vibronic structure is observed in the two-photon spectra for all porphyrinoids investigated, but their relative intensities show distinct differences from the vibronic development observed in the corresponding one-photon spectra. A Franck–Condon analysis provides insight into the observed differences. The calculations also indicate that the two-photon absorptivities are associated primarily with Type I processes involving multiple intermediate states, and that accurate assignment requires a summation over at least 30 intermediate st...

Cyclic 2,12-porphyrinylene nanorings as a porphyrin analogue of cycloparaphenylenes.

β-to-β Directly linked cyclic Ni(II) porphyrin trimer, tetramer, and pentamer ([3]CP, [4]CP, and [5]CP) have been synthesized by reaction of a 2,12-diborylated Ni(II) porphyrin with Pt(cod)Cl2 followed by reductive elimination. The structures of these cyclic porphyrin arrays have been revealed by X-ray diffraction analysis. The strain energies of these cyclic oligomers are calculated to be 77, 57, and 47 kcal/mol for [3]CP, [4]CP, and [5]CP, respectively. Intramolecular excitation energy hopping was observed between the (3)(d,d) states of the Ni(II) porphyrins with rates of 3.0, 4.4, and 4.6 ps for [3]CP, [4]CP, and [5]CP, respectively, reflecting the close proximity of the Ni(II) centers.

Molecular structures, redox properties, and photosubstitution of ruthenium(II) carbonyl complexes of porphycene

Two ruthenium(II) carbonyl complexes of porphycene, (carbonyl)(pyridine)(2,7,12,17-tetra-n-propylporphycenato)ruthenium(II) (1) and (carbonyl)(pyridine)(2,3,6,7,12,13,16,17-octaethylpor-phycenato)ruthenium(II) (2), have been structurally characterized by single-crystal X-ray diffraction analysis. Cyclic voltammetry has revealed that the porphycene complexes undergo multiple oxidations and reductions in dichloromethane and the reduction potentials are highly positive compared to porphyrin analogs. UV-light irradiation (400 nm or shorter wavelength region) of a benzene solution of 1 and 2 containing external pyridine leads to dissociation of the carbonyl ligand from the ruthenium(II) centers to give the corresponding bis-pyridine complexes. The identical reaction has been also studied for a porphyrin derivative (carbonyl)(pyridine)(2,3,7,8,12,13,17,18-octaethylporphyriato)ruthenum(II) (3). The first-order kinetic analysis has revealed that the photosubstitution of all of the compounds occurs in the order of 10-3 s-1 at 298 K but proceeds faster for complexes of porphycene (1 and 2) than that of porphyrin (3).

Abstract 2510: A porphodimethene chemical inhibitor of uroporphyrinogen decarboxylase

Abstract Uroporphyrinogen decarboxylase (UROD), a heme biosynthetic pathway enzyme that converts uroporphyrinogen to coproporphyrinogen, was recently identified as a potential anticancer target. UROD inhibition leads to an increase in reactive oxygen species (ROS), likely mediated by the Fenton reaction, which decreases cancer cell viability and sensitizes cells to cisplatin and radiation. Because there is no known chemical UROD inhibitor suitable for translational research, we aimed to design, synthesize, and characterize such a compound. In silico design and docking was used to identify a potential porphyrin analogue. Subsequent synthesis produced a porphodimethene (named PI-16) that inhibited UROD in an enzymatic assay (IC50 = 9.9 µM). PI-16 did not affect porphobilinogen deaminase (at 62.5 µM), thereby exhibiting some specificity. In cellular assays, PI-16 reduced FaDu and ME-180 cancer cell viability with half maximal effective concentrations of 22.7 µM and 26.9 µM, respectively, whereas normal oral epithelial (NOE) cells were only minimally affected. PI-16 combined effectively with cisplatin and radiation, with potent synergy being observed with cisplatin (Chou-Talalay combination index < 1). This work presents the first known synthetic UROD inhibitor, and sets the foundation for the design, synthesis, and characterization of higher affinity and more effective compounds. Citation Format: Kenneth W. Yip, Zhan Zhang, Noriko Sakemura-Nakatsugawa, Jui-Wen Huang, Shijun Yue, Yulia Jitkova, Terence To, Emil Pai, Aaron Schimmer, Jonathan Lovell, Jonathan Sessler, Fei-Fei Liu. A porphodimethene chemical inhibitor of uroporphyrinogen decarboxylase. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2510. doi:10.1158/1538-7445.AM2014-2510