Journal of Porphyrins and Phthalocyanines

Combinatorial libraries of substituted tetrapyrrole macrocycles, which can now be prepared via a variety of approaches, typically are rich in isomers. Terminology for describing such isomers (due to distinct patterns of peripheral substituents) is delineated in several illustrative examples. A hierarchical relationship exists of molecular formula, condensed formula(s) of substituents, set(s) of pyrrole collocates (conveying each pair of β-pyrrolic substituents), and isomers of substituted tetrapyrrole macrocycles. Isomers with identical pyrrole collocate sets can arise owing to distinct positions or orientations of the (homo- or hetero-substituted) pyrrolic units in a macrocycle. Consideration of a handful of virtual combinatorial libraries illustrates tradeoffs of library size, chemical richness, and isomeric content. As one example, octa-derivatization of a tetrapyrrole scaffold with eight reactants A–H affords 2,099,728 members (99.7% isomers, 82,251 pyrrole collocate sets, and 6,435 condensed formulas) whereas the reversible self-condensation of four pyrroles that bear the same eight entities (AB, CD, EF, GH) affords 538 members (93.5% isomers, 35 pyrrole collocate sets, and 35 condensed formulas). Derivatization affords all combinations and permutations whereas self-condensation of substituted pyrroles carries collocational restrictions. Understanding such tradeoffs and the structural origin of isomerism are important aspects in the design of tetrapyrrole combinatorial libraries.

The present article examines the binding affinity of the newly designed Zn₂-bisporphyrin molecule, syn-1, towards C₆₀ and C₇₀ in toluene medium. The investigation is carried out by UV-vis spectrophotometric, steady state and time-resolved fluorescence spectroscopic techniques. The bisporphyrin, syn-1, serves as an effective and selective molecular tweezer for C₇₀ as average value of binding constants (K) for the non-covalent complexes of syn-1 with C₆₀ and C₇₀ are estimated to be 1.65 × 10⁴ and 1.05 × 10⁵ dm³ · mol^-1, respectively. Binding of C₇₀ in the cleft of syn-1 is clearly demonstrated by the quantum chemical calculations at ab initio level of theory. Molecular electrostatic potential maps demonstrate significant redistribution of charges in these supramolecules. Proton NMR studies suggest that the C₇₀ moiety remains at the shallow part of the cleft of syn-1.

The activation of cobalamin requires a reduction from cobalamin(III) to cobalamin(II). The reduction by glutathione and dithiothreitol was followed using visible spectroscopy and electron paramagnetic resonance. In addition the oxidation of glutathione was monitored. Glutathione first reacts with oxidized cobalamin(III). The binding of a second glutathione required for the reduction to cobalamin(II) is presumably located in the dimethyl benzimidazole ribonucleotide ligand cavity. The reduction of cobalamin(III) by dithiothreitol, which contains two thiols, is much faster even though no stable cobalamin(III) complex is formed. The reduction, by both thiol reagents, results in the formation of thiyl radicals, some of which are released to form oxidized thiol products and some of which remain associated with the reduced cobalamin. In the reduced state the intrinsic lower affinity for the benzimidazole base, coupled with a trans effect from the initial glutathione bound to the β-axial site and a possible lowering of the pH results in an equilibrium between base-on and base-off complexes. The dissociation of the base facilitates a closer approach of the thiyl radical to the cobalamin(II) α-axial site resulting in a complex with ferromagnetic exchange coupling between the metal ion and the thiyl radical. This is a unique example of "internal spin trapping" of a thiyl radical formed during reduction. The finding that the reduction involves a peripheral site and that thiyl radicals produced during the reduction remain associated with the reduced cobalamin provide important new insights into our understanding of the formation and function of cobalamin enzymes.

The two-dimensional ¹H, ¹³C and ¹H, ¹⁵N heteronuclear single quantum coherence (HSQC) and heteronuclear multiple bond correlation (HMBC) NMR techniques were applied to investigate the formation of N-protonated cationic species of methyl pyropheophorbide a in methanolic hydrochloric acid (CD₃OH-HCl). The ¹H, ¹³C HSQC and ¹H, ¹⁵N HMBC NMR spectra, recorded at the temperature of 278 K, verified that the CD₃OH-HCl solution with [H]⁺ = 0.021 M, contained the N22-protonated monocations of methyl pyropheophorbide a, whereas the CD₃OH-HCl solution with [H]⁺ = 5.0 M contained the N22, N24-protonated dications of the phorbin. No further protonations to form the trication or tetracation were observed. Consequently, the two middle electronic spectra, which were previously tentatively interpreted as representing the dication and trication, were now attributed to conformational alterations originating from steric hindrance between the central hydrogens and changes in counter-ion and solvation interactions and/or conformational alterations intimately connected to NH-tautomerism. These possibilities to explain the previously observed middle electronic spectra are briefly discussed.

Results are reported from investigations of the interactions between MS2 bacteriophages and a cationic porphyrin with potential use in photodynamic therapy. Based on the naturally strong binding between porphyrins and nucleic acids, it is suggested that this non-enveloped capsid could act as a self-loading, nanoscale carrier of porphyrins. By applying size exclusion chromatography in conjunction with UV-vis and fluorescence spectroscopy, it is demonstrated that approximately 250 porphyrin molecules could associate and co-elute with a single capsid. Additionally, there is an observed red shift in the Soret peak of the porphyrin, indicating that the majority of the cationic porphyrin is capable of interacting with RNA on the interior of the capsid. It is also observed that removal of RNA from the interior of the MS2 capsid significantly reduces loading capacity of the porphyrin. Furthermore, MS2 bacteriophages loaded with porphyrins were shown to photogenerate singlet oxygen. These findings suggest that icosahedral viruses, such as MS2 bacteriophages, are able to function as self-packaging "nanoscale containers" and efficiently load cationic porphyrins, with potential benefits in areas such as targeted photodynamic therapy.

The photodynamic properties of eight hydrophobic monocationic methyl and ruthenium polypyridine complex derivatives of free-base and zinc(II) meso-triphenyl-monopyridylporphyrin series were evaluated and compared using HeLa cells as model. The cream-like polymeric nanocapsule formulations of marine atelocollagen/xanthan gum, prepared by the coacervation method, exhibited high phototoxicity but negligible cytotoxicity in the dark. Interestingly, the formulations of a given series presented similar photodynamic activities but the methylated free-base derivatives were significantly more phototoxic than the respective ruthenated photosensitizers, reflecting the higher photoinduced singlet oxygen quantum yields of those monocationic porphyrin dyes.

The present study is designed to investigate the effect of lipophilicity of ¹⁰⁹Pd-porphyrin complexes on their biological properties which were evaluated in tumor-bearing animal model. The insight obtained could be utilized to develop other radiometalated porphyrin complexes with optimum tumor uptake and tumor to background ratio as potential agents for targeted tumor therapy. ¹⁰⁹Pd was produced by thermal neutron bombardment on enriched (in ¹⁰⁹Pd) metallic palladium target at a flux of 3 × 10¹³ n/cm².s for 3 d. ¹⁰⁹Pd complexes of three different porphyrin derivatives, namely, 5,10,15,20-tetrakis[3,4- bis(carboxymethyleneoxy)phenyl]porphyrin(I), 5,10,15,20-tetrakis[3,4-bis(carboethoxymethyleneoxy)phenyl]porphyrin(II) and 5,10,15,20-tetrakis[4-carboxymethyleneoxyphenyl]porphyrin(III), which differ in their peripheral substituents, were synthesized. The biological behavior of the complexes was studied in Swiss mice bearing fibrosarcoma tumors. ¹⁰⁹Pd was produced with a specific activity of ~1.85 GBq/mg (50 mCi/mg) and radionuclidic purity of 100%. All the ¹⁰⁹Pd complexes were obtained in high yield (>97%) and they exhibited satisfactory in vitro stability at room temperature. The lipophilicity of the complexes follows the order ¹⁰⁹Pd-II ≫ ¹⁰⁹Pd-III > ¹⁰⁹Pd-I. Biodistribution studies revealed that the most lipophilic ¹⁰⁹Pd-II complex exhibited highest initial tumor uptake but poor tumor/liver ratio, while ¹⁰⁹Pd-III complex exhibited the best tumor/liver ratio with reasonably good tumor accumulation. The lipophilicity of ¹⁰⁹Pd-porphyrin complexes was found to have considerable effect on their biological characteristics and radiometal-porphyrin complexes with optimum tumor uptake and adequately high tumor to background ratio could be synthesized by optimization of the lipophilicity through proper selection of peripheral substituents.

A series of simple logic gates based on a water-soluble porphyrin molecule, 5,10,15,20-tetrakis-(4-sulfonatophenyl)porphyrin (TPPS₄) is designed. Logic operations, including OR, NOR, INHIBIT and AND, have been built by two inputs of acid/base or metal ions (Al³⁺ and/or Sn⁴⁺) and two outputs of UV-vis absorption and fluorescent spectra. An OFF–ON switch triggered by Al³⁺ ion in vitro is developed based on TPPS₄.

In order to develop a novel near infrared fluorescence agent, glucose conjugated zinc phthalocyanine, [2,9(10),16(17),23(24)-tetrakis((1-(β-D-glucopyranose-2-yl)-1H-1,2,3-triazol-4-yl)methoxyl)phthalocyaninato]zinc(II), was synthesized via Click reaction. Their chemical structures were characterized by mass spectrometry, nuclear magnetic resonance spectrum. Their light stability and fluorescence quantum yield were evaluated by UV-visible and fluorescent spectroscopic method. Optical imaging in vivo was performed with this saccharide conjugated phthalocyanine as probe on liver tumor-bearing nude mice. Near-infrared imaging effect, organ aggregation as well as distribution of probe in vivo were evaluated by in vivo fluorescence imaging technique. Results show that glucose conjugated zinc phthalocyanine has favorable water solubility, good optical stability and high emission ability in near infrared region. Imaging results demonstrate that saccharide conjugated phthalocyanine has possess obvious imaging effect in vivo, which implies its potential in cancer diagnosis as near infrared optical probe.

5,10,15,20-tetrakis(4-amidinophenyl)porphyrin (Por 1), its Zn complex (Por 2) and its conjugate with a tetraphenylporphyrin to form a bisporphyrin (Por 3) were prepared. The monomeric Por 1 and Por 2 showed both intercalative and external binding with DNA whereas only external DNA binding was seen in the bisporphyrin, Por 3 by circular dichroism and UV-vis. The DNA photocleavage activities of these porphyrins followed the order: Por 1 ~ Por 2 > Por 3, which did not correlate with their measured ¹O₂ production rates. It suggests 4-amidinophenylporphyrins are promising new photodynamic therapeutic agents.

A variety of aromatic and aliphatic aldehydes were oxidized to the corresponding carboxylic acids in the presence of platinum porphyrin, sunlight and air in acetonitrile solvent under mild conditions. Nitrobenzaldehydes were found to be very efficient ¹O₂ scavengers that quench the formation of acids from any aldehyde in the presence of free-base porphyrin sensitizers. However, nitrobenzaldehydes were converted to the corresponding acids in the presence of platinum porphyrins. The platinum porphyrins are very good and efficient catalysts for a wide range of applications in the aerobic conversion of aldehydes to acids.

Several cationic beta-vinyl-pyridinium and beta-vinyl-quinolinium-meso-tetraphenylporphyrin derivatives were synthesized starting from 2-formyl-meso-tetraphenylporphyrin, and the corresponding Zn(II) complex, and different N-alkyl derivatives of 2- and 4-methylpyridine and 2- and 4-methylquinoline. The new compounds were obtained in a one-step process via base catalyzed aldol-type condensation reactions. Electrospray ionization mass spectrometry (ESI-MS) and ultraviolet-visible (UV-vis) spectroscopy were used to investigate the binding mode of the synthesized cationic beta-vinyl-pyridinium and beta-vinyl-quinolinium-meso-tetraphenylporphyrin derivatives with a short GC duplex oligonucleotide. Analysis of the obtained mass spectrometry results indicates the probable occurrence of outside binding. UV-vis spectroscopy data also points to non-intercalation. The potential photosensitizing capacity of these compounds was also ascertained from preliminary photophysical studies.

We prepared [meso-tetrakis(4-carboxylatophenyl)porphyrinato]oxovanadium(IV) tetrasodium, ([VO(tcpp)]Na₄), and investigated its in vitro insulin-mimetic activity and in vivo metallokinetic feature in healthy rats. The results were compared with those of previously proposed insulin-mimetic oxovanadium(IV)porphyrin complexes and oxovanadium(IV) sulphate. The in vitro insulin-mimetic activity and bioavailability of [VO(tcpp)]Na₄ were considerably better than those of [meso-tetrakis (1-methylpyridinium-4-yl)porphyrinato]oxovanadium(IV)(4+) tetraperchlorate ([VO(tmpyp)](ClO₄)₄) and oxovanadium(IV) sulphate. On the other hand, [VO(tcpp)]Na₄ and [meso-tetrakis(4-sulfonatophenyl) porphyrinato]oxidovanadate(IV)(4-)([VO(tpps)]) showed very similar in vitro insulin-mimetic activity and in vivo metallokinetic feature in healthy rats. In particular, the order of in vitro insulin-mimetic activity of the complexes was determined to be: [VO(tcpp)]Na₄ ≈ [VO(tpps)] > ([VO(tmpyp)](ClO₄)₄ > oxovanadium(IV) sulphate.

A series of novel chlorophyll-a homologs with long wavelength absorption were synthesized via modification of methyl pyropheophorbide-a used as starting material. For introducing electron-withdrawing group methylenemalononitrile moiety was established on the periphery of modified chlorin by Knoevenagel reaction of malononitrile with formyl group at 3-, 15-position and 13¹-carbonyl group on the exocyclic ring. All of chlorins containing the methylenemalononitrile structure show Qy-absorption at more than 700 nm. Moreover, we have examined a preliminary in vitro photodynamic anticancer effect of these new derivatives on mouse sarcoma S-180 cell line.

In this work we report on electrochemical behavior of nickel phthalocyanine derivatives tetrasubstituted peripherally and non-peripherally with hydroxy and used to modify single walled carbon nanotubes. Nickel phthalocyanine complex octasubstituted at the peripheral positions with hydroxy groups was also used to modify single walled carbon nanotubes. Nickel phthalocyanine complex tetrasubstituted with amino groups at peripheral position was covalently and non-covalently linked to single walled carbon nanotubes. All the conjugates of nickel phthalocyanine derivatives with single walled carbon nanotubes were used for the electro oxidation of 4-chlorophenol. The nickel phthalocyanine octabsubstituted with hydroxy groups at the non-peripheral positions gave the best current response and the best resistance against electrode fouling for the oxidation of 4-chlorophenol.

We present our results from the experimental and modeling studies of picosecond (ps) and femtosecond (fs) nonlinearities of two novel corroles (a) tritolyl corrole (TTC) (b) triphenyl corrole (TPC) using the Z-scan technique. Both open and closed aperture Z-scan curves were recorded with ~2 ps/~40 fs laser pulses at a wavelength of 800 nm and nonlinear optical coefficients were extracted for both studies. Both the molecules possessed negative nonlinear refractive index (n₂) as revealed by signature of the closed aperture data in both (ps and fs) time domains. Picosecond nonlinear absorption data of TPC obtained at a concentration of 5 × 10^-4 M demonstrated complex behavior with switching from reverse saturable absorption (RSA) within saturable absorption (SA) at lower peak intensities to RSA at higher peak intensities. TTC data recorded at the similar concentration exhibited saturable absorption (SA) type of behavior at lower peak intensities to switching from RSA with in SA at higher peak intensities. At a concentration of 2.5 × 10^-4 M, the ps open aperture data at higher peak intensities illustrated effective three-photon absorption (3PA) for both the molecules. We also report the picosecond spectral dependent Z-scan studies performed at 680 nm, 700 nm, and 740 nm. Nonlinear absorption and refraction of both the samples at these three wavelengths were studied in detail. Femtosecond nonlinear absorption data of TPC and TTC demonstrated the behavior of saturable absorption (SA) at a concentration of 1 × 10^-3 M. Solvent contribution to the nonlinearity was also identified. We have also evaluated the sign and magnitude of third order nonlinearity. We discuss the nonlinear optical performance of these organic molecules.

The epoxidation of cis-stilbene by n-Bu₄NHSO₅ was studied in the presence of two different manganese porphyrin complexes, [MnTPFPP(Cl) and MnTPP(Cl)], and various n-Bu₄NX (X = OAc, F, Cl, Br, OCN, NO₃, BF₄). In general direct correlation was found between stereoselectivity of the epoxidation reaction and the nucleophilic properties of these anionic co-catalysts. Also epoxidation of naphthalene was carried out in high yield and good selectivity by n-Bu₄NHSO₅ in the presence of MnTPFPP(Cl) in association with n-Bu₄NOAc or n-Bu₄NF co-catalysts.

The reduction of magnesium phthalocyanine (MgPc) with 2.2 equivalents of potassium graphite in 1,2-dimethoxyethane (DME) gives [K₂(DME)₄]PcMg(OH)(1) in 67% yield. Compound 1 was structurally characterized using single crystal X-ray crystallography and was found to be a monomeric, heterometallic complex consisting of a μ₃-OH ligand that bridges a [Mg^IIPc^3-]^- anion to two potassium cations solvated by four DME molecules. An absorption spectrum of 1 confirms the Pc ligand is singly reduced and has a 3–charge. The solid-state structure of 1 does not indicate breaking of the aromaticity of the Pc ligand. Compound 1 is only the second Pc^3- complex and the first reduced MgPc to be isolated and structurally characterized.

This work reports on the synthesis of novel metal free, zinc, aluminum, gallium and indium tetra and octa (2,6-di-iso-propylphenoxy)-substituted phthalocyanine derivatives. UV-visible and ¹H NMR analyses confirm that a non-planar conformation, adapted by the phenoxy substituents due to steric interaction in both derivative series, perfectly discourage cofacial aggregation. Fluorescence quantum yields vary as a function of the number of substituents on the ring periphery, while the fluorescence lifetimes display no distinct trend. Triplet quantum yields are significantly larger for the tetra 2,6-di-iso-propylphenoxy- substituted derivatives relative to their corresponding octa-substituted species. However there was no overall trend in the triplet lifetime values. For almost all of the phthalocyanine derivatives, singlet oxygen was produced with relatively good quantum yields. This study explores the possibility of fine-tuning their physicochemical properties by simple structural modification.