bacteriochlorin and chlorin

Topics: Porphyrins; Pyrroles; Tetrapyrroles

Erlotinib was covalently linked to 3-(1'-hexyloxy)ethyl-3-devinylpyropheophorbide-a (HPPH) and structurally related chlorins and bacteriochlorins at different positions of the tetrapyrrole ring. The functional consequence of each modification was determined by quantifying the uptake and subcellular deposition of the erlotinib conjugates, cellular response to therapeutic light treatment in tissue cultures, and in eliminating of corresponding tumors grown as a xenograft in SCID mice. The experimental human cancer models the established cell lines UMUC3 (bladder), FaDu (hypopharynx), and primary cultures of head and neck tumor cells. The effectiveness of the compounds was compared to that of HPPH. Furthermore, specific functional contribution of the carboxylic acid side group at position 17

Topics: Animals; Cell Line, Tumor; Cell Survival; Coculture Techniques; Erlotinib Hydrochloride; Female; Head and Neck Neoplasms; Humans; Mice; Mice, SCID; Photochemotherapy; Photosensitizing Agents; Porphyrins; Stereoisomerism; Structure-Activity Relationship; Survival Rate

Molecules or ions are either paramagnetic (unpaired electrons) or diamagnetic (all electrons are paired). Switching between the two states under ambient conditions was considered a typical solid state phenomenon and has been termed spin crossover. The first single-molecule spin state switches operated with light in solution were developed a decade ago and offer a number of technical applications that are not accessible to solid state systems. Magnetic switching in biological environments, however, requires water solubility, and for

Topics: Isomerism; Porphyrins

A series of chlorin-bacteriochlorin dyads (derived from naturally occurring chlorophyll-a and bacteriochlorophyll-a), covalently connected either through the meso-aryl or β-pyrrole position (position-3) via an ester linkage have been synthesized and characterized as a new class of far-red emitting fluorescence resonance energy transfer (FRET) imaging, and heavy atom-lacking singlet oxygen-producing agents. From systematic absorption, fluorescence, electrochemical, and computational studies, the role of chlorin as an energy donor and bacteriochlorin as an energy acceptor in these wide-band-capturing dyads was established. Efficiency of FRET evaluated from spectral overlap was found to be 95 and 98 % for the meso-linked and β-pyrrole-linked dyads, respectively. Furthermore, evidence for the occurrence of FRET from singlet-excited chlorin to bacteriochlorin was secured from studies involving femtosecond transient absorption studies in toluene. The measured FRET rate constants, k

Topics: Fluorescence Resonance Energy Transfer; Porphyrins; Pyrroles; Singlet Oxygen

C3-(Trans-2-arylethenyl)carbonylated chlorophyll derivatives possessing a bacteriochlorin or chlorin π-system were synthesized by cross-aldol (Claisen-Schmidt) condensation of methyl pyrobacteriopheophorbide-a or 3-acetyl-3-devinyl-pyropheophorbide-a bearing the C3-acetyl group with p-(un)substituted benzaldehydes under basic conditions. The corresponding porphyrin-type chlorophyll derivatives were prepared by the oxidation (17,18-didehydrogenation) of the chlorin-type. Their Qy absorption and fluorescence emission maxima in dichloromethane correlated well with Hammett substituent constants of the p-substituents. Several electron-withdrawing p-substituents suppressed the emission due to photoinduced electron transfer quenching in a molecule. The substitution sensitivities for their maxima and fluorescence quantum yields decreased in the order of bacteriochlorin-, chlorin- and porphyrin-type derivatives.

Topics: Chalcone; Chlorophyll; Mass Spectrometry; Porphyrins; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet

Optical data (UV-vis absorption and fluorescence emission spectra, including fluorescence yields and lifetimes) and electrochemical measurements are used to quantify the modulation of the electronic properties of meso-tetrakis(pentafluorophenyl)-chlorin diol and -bacteriochlorin tetraols upon intramolecular chromene-annulation, including the investigation of regio- and stereoisomers. The small modulations of the frontier orbitals of the porphyrinoids are rationalized using DFT computations and can be traced to small electronic effects due to the co-planarized meso-aryl groups in combination with conformational effects.

Topics: Benzopyrans; Electrons; Models, Molecular; Molecular Conformation; Molecular Structure; Porphyrins; Quantum Theory; Stereoisomerism

Topics: Animals; Cell Survival; Dose-Response Relationship, Drug; Esophageal Neoplasms; Female; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Structure; Neoplasms, Experimental; Photochemotherapy; Photosensitizing Agents; Porphyrins; Structure-Activity Relationship; Tumor Cells, Cultured

A Diels-Alder strategy is reported to synthesize the complete set of hydroporphyrins: chlorins, bacteriochlorins, isobacteriochlorins, and pyrrocorphins. Porphyrins and Ni-porphyrins react with isobenzofuran in very high yields at 70 °C to form the corresponding chlorins. Electron-deficient porphyrins react with a second equivalent of isobenzofuran yielding exclusively bacteriochlorin (82%), and Ni-porphyrin gives only isobacteriochlorin (99%). All cycloadditions are completely regio- and stereoselective. The regiochemistry is correctly predicted using the ACID method.

Topics: Models, Molecular; Molecular Structure; Porphyrins; Stereoisomerism

The combination of a photosensitizer (PS) with a cisplatin-like unit represents a challenging strategy to increase the effectiveness of photodynamic therapy and to afford a dual-action anticancer treatment. Recently, new tetra-Pt

Topics: Antineoplastic Agents; Coloring Agents; Coordination Complexes; Light; Models, Molecular; Photosensitizing Agents; Platinum; Porphyrins; Quantum Theory

Achieving tunable, intense near-infrared absorption in molecular architectures with properties suitable for solar light harvesting and biomedical studies is of fundamental interest. Herein, we report the photophysical, redox, and molecular-orbital characteristics of nine hydroporphyrin dyads and associated benchmark monomers that have been designed and synthesized to attain enhanced light harvesting. Each dyad contains two identical hydroporphyrins (chlorin or bacteriochlorin) connected by a linker (ethynyl or butadiynyl) at the macrocycle β-pyrrole (3- or 13-) or meso (15-) positions. The strong electronic communication between constituent chromophores is indicated by the doubling of prominent absorption features, split redox waves, and paired linear combinations of frontier molecular orbitals. Relative to the benchmarks, the chlorin dyads in toluene show substantial bathochromic shifts of the long-wavelength absorption band (17-31 nm), modestly reduced singlet excited-state lifetimes (τS = 3.6-6.2 ns vs 8.8-12.3 ns), and increased fluorescence quantum yields (Φf = 0.37-0.57 vs 0.34-0.39). The bacteriochlorin dyads in toluene show significant bathochromic shifts (25-57 nm) and modestly reduced τS (1.6-3.4 ns vs 3.5-5.3 ns) and Φf (0.09-0.19 vs 0.17-0.21) values. The τS and Φf values for the bacteriochlorin dyads are reduced substantially (up to ∼20-fold) in benzonitrile. The quenching is due primarily to the increased S1 → S0 internal conversion that is likely induced by increased contribution of charge-resonance configurations to the S1 excited state in the polar medium. The fundamental insights gained into the physicochemical properties of the strongly coupled hydroporphyrin dyads may aid their utilization in solar-energy conversion and photomedicine.

Topics: Porphyrins; Spectrometry, Fluorescence

Syntheses and optical properties of mono- and bis-chromene-annulated bacteriochlorins are described. Known monochromene-annulated meso-(pentafluorophenyl)chlorin is susceptible to a regioselective OsO4-mediated dihydroxylation, generating two monochromene-annulated trihydroxybacteriochlorin stereoisomers: either the newly introduced vic-cis-diol functionality is on the same side as the vic-cis-diol moiety the chromene-annulation was based on or on the opposite side. Treatment of the two isomers with heat or base generates different sets of bis-chromene-annulated bacteriochlorin stereo- and regioisomers. Detailed 1D and 2D (1)H and (19)F NMR spectroscopic investigations allowed the characterization of the isomers that formed. The regioselectivity of the second annulation reaction was rationalized computationally on steric grounds. The bacteriochlorin-type optical spectra of the mono- and bis-chromene-annulated bacteriochlorins are modulated as a result of the annulation, with each isomer possessing a unique spectrum, attributed to the effects the regiochemically distinct annulations have on the conformation of the chromophore. The formation of a bis-chromene-annulated chlorin from the bacteriochlorins is also described, including its X-ray crystal structure, revealing some details of the metrics of the chromene-annulated moiety. The vic-diol functionality of monochromene-annulated trihydroxybacteriochlorins is also susceptible to oxidation and ring-expansion reactions, generating chromene-annulated pyrrole-modified chlorins incorporating oxazolone and morpholine moieties. The work expands the body of work on the synthesis and optical fine-tuning of meso-aryl-substituted bacteriochlorins.

Topics: Benzopyrans; Crystallography, X-Ray; Isomerism; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Oxazolone; Oxidation-Reduction; Porphyrins; Pyrroles

Efficient light harvesting for molecular-based solar-conversion systems requires absorbers that span the photon-rich red and near-infrared (NIR) regions of the solar spectrum. Reported herein are the photophysical properties of a set of six chlorin-imides and nine synthetic chlorin analogues that extend the absorption deeper (624-714 nm) into these key spectral regions. These absorbers help bridge the gap between typical chlorins and bacteriochlorins. The new compounds have high fluorescence quantum yields (0.15-0.34) and long singlet excited-state lifetimes (4.2-10.9 ns). The bathochromic shift in Qy absorption is driven by substituent-based stabilization of the lowest unoccupied molecular orbital, with the largest shifts for chlorins that bear an electron-withdrawing, conjugative group at the 3-position in combination with a 13,15-imide ring.

Topics: Electrons; Fluorescence; Imides; Molecular Structure; Photochemical Processes; Porphyrins; Quantum Theory

Lipid vesicles are used as the organizational structure of self-assembled light-harvesting systems. Following analysis of 17 chromophores, six were selected for inclusion in vesicle-based antennas. The complementary absorption features of the chromophores span the near-ultraviolet, visible, and near-infrared region. Although the overall concentration of the pigments is low (~1 μM for quantitative spectroscopic studies) in a cuvette, the lipid-vesicle system affords high concentration (≥10 mM) in the bilayer for efficient energy flow from donor to acceptor. Energy transfer was characterized in 13 representative binary mixtures using static techniques (fluorescence-excitation versus absorptance spectra, quenching of donor fluorescence, modeling emission spectra of a mixture versus components) and time-resolved spectroscopy (fluorescence, ultrafast absorption). Binary donor-acceptor systems that employ a boron-dipyrrin donor (S0 ↔ S1 absorption/emission in the blue-green) and a chlorin or bacteriochlorin acceptor (S0 ↔ S1 absorption/emission in the red or near-infrared) have an average excitation-energy-transfer efficiency (ΦEET) of ~50%. Binary systems with a chlorin donor and a chlorin or bacteriochlorin acceptor have ΦEET ∼ 85%. The differences in ΦEET generally track the donor-fluorescence/acceptor-absorption spectral overlap within a dipole-dipole coupling (Förster) mechanism. Substantial deviation from single-exponential decay of the excited donor (due to the dispersion of donor-acceptor distances) is expected and observed. The time profiles and resulting ΦEET are modeled on the basis of (Förster) energy transfer between chromophores relatively densely packed in a two-dimensional compartment. Initial studies of two ternary and one quaternary combination of chromophores show the enhanced spectral coverage and energy-transfer efficacy expected on the basis of the binary systems. Collectively, this approach may provide one of the simplest designs for self-assembled light-harvesting systems that afford broad solar collection and efficient energy transfer.

Topics: Boron; Computer Simulation; Fluorescence Resonance Energy Transfer; Kinetics; Light-Harvesting Protein Complexes; Lipid Bilayers; Models, Chemical; Phosphatidylcholines; Photochemical Processes; Porphyrins; Spectrum Analysis; Unilamellar Liposomes

Zinc complex of pyropheophorbide-b, a derivative of chlorophyll-b, was covalently dimerized through ethylene glycol diester. The synthetic homo-dyad was axially ligated with two methanol molecules from the β-face and both the diastereomerically coordinating methanol species were hydrogen bonded with the keto-carbonyl groups of the neighboring chlorin in a complex. The resulting folded conformer in a solution was confirmed by visible, (1) H NMR and IR spectra. All the synthetic zinc chlorin homo- and hetero-dyads consisting of pyropheophorbides-a, b and/or d took the above methanol-locked and π-π stacked supramolecules in 1% (v/v) methanol and benzene to give redmost (Qy) electronic absorption band(s) at longer wavelengths than those of the corresponding monomeric chlorin composites. The other zinc chlorin and bacteriochlorin homo-dyads completely formed similar folded conformers in the same solution, while zinc inverse chlorin and porphyrin homo-dyads partially took such supramolecules. The J-type aggregation to folded conformers and the redshift values of composite Qy bands were dependent on the electronic and steric factors of porphyrinoid moieties in dyads.

Topics: Chlorophyll; Molecular Conformation; Porphyrins; Zinc

The synthesis, photophysical, redox, and molecular-orbital characteristics of three perylene-tetrapyrrole dyads were investigated to probe the efficacy of the arrays for use as light-harvesting constituents. Each dyad contains a common perylene-monoimide that is linked at the N-imide position via an arylethynyl group to the meso-position of the tetrapyrrole. The tetrapyrroles include a porphyrin, chlorin, and bacteriochlorin, which have zero, one, and two reduced pyrrole rings, respectively. The increased pyrrole-ring reduction results in a progressive red shift and intensification of the lowest-energy absorption band, as exemplified by benchmark monomers. The arylethyne linkage affords moderate perylene-tetrapyrrole electronic coupling in the dyads as evidenced by the optical, molecular-orbital, and redox properties of the components of the dyads versus the constituent parts. All three dyads in nonpolar solvents exhibit relatively fast (subpicosecond) energy transfer from the perylene to the tetrapyrrole. Competing charge-transfer processes are also absent in nonpolar solvents, but become active for both the chlorin and bacteriochlorin-containing dyads in polar solvents. Calculations of energy-transfer rates via the Förster, through-space mechanism reveal that these rates are, on average, 3-fold slower than the observed rates. Thus, the Dexter through-bond mechanism contributes more substantially than the through-space mechanism to energy transfer in the dyads. The electronic communication between the perylene and tetrapyrrole falls in a regime intermediate between those operative in other classes of perylene-tetrapyrrole dyads that have previously been studied.

Topics: Absorption; Electric Power Supplies; Electrons; Energy Transfer; Light; Models, Molecular; Molecular Conformation; Oxidation-Reduction; Perylene; Porphyrins; Tetrapyrroles

(Bacterio)Chlorophyll ((B)Chl) molecules play a major role in photosynthetic light-harvesting proteins, and the knowledge of their triplet state energies is essential to understand the mechanisms of photodamage and photoprotection, as the triplet excitation energy of (B)Chl molecules can readily generate highly reactive singlet oxygen. The triplet state energies of 10 natural chlorophyll (Chl a, b, c2, d) and bacteriochlorophyll (BChl a, b, c, d, e, g) molecules and one bacteriopheophytin (BPheo g) have been directly determined via their phosphorescence spectra. Phosphorescence of four molecules (Chl c2, BChl e and g, BPheo g) was characterized for the first time. Additionally, the relative phosphorescence to fluorescence quantum yield for each molecule was determined. The measurements were performed at 77K using solvents providing a six-coordinate environment of the Mg(2+) ion, which allows direct comparison of these (B)Chls. Density functional calculations of the triplet state energies show good correlation with the experimentally determined energies. The correlation determined computationally was used to predict the triplet energies of three additional (B)Chl molecules: Chl c1, Chl f, and BChl f.

Topics: Bacteria; Bacteriochlorophylls; Electron Spin Resonance Spectroscopy; Energy Transfer; Photosynthesis; Porphyrins; Quantum Theory; Rhodobacter sphaeroides; Singlet Oxygen; Spectrometry, Fluorescence

The synthesis, photophysical, redox, and molecular-orbital characteristics of three perylene-tetrapyrrole dyads were investigated to elucidate characteristics favorable for use in next-generation light-harvesting assemblies. Each dyad contains a common perylene-monoimide that is linked at the 9-position via an ethynyl group to the meso-position of the tetrapyrrole. The tetrapyrroles include a porphyrin, chlorin, and bacteriochlorin, which have zero, one, and two reduced pyrrole rings, respectively. The increased pyrrole-ring reduction results in a progressive red shift and intensification of the lowest-energy absorption band, as exemplified by benchmark monomers. The direct ethyne linkage and accompanying strong perylene-tetrapyrrole electronic coupling in the dyads is evident by significant differences in optical absorption versus the sum of the features of the constituents. The perturbations decrease for the tetrapyrrole constituent along the series porphyrin > chlorin > bacteriochlorin. This trend is explained by the relative configurational mixing in the tetrapyrrole excited states and how the configuration-interaction energy (and not simply the energies of the configurations) is affected by coupling to the perylene. The perylene-tetrapyrrole electronic coupling is further evidenced in the redox and MO characteristics of the three dyads. All three dyads in nonpolar solvents exhibit relatively long singlet excited-state lifetimes (3.3-6.5 ns) and relatively large fluorescence quantum yields (0.14-0.40). Collectively, the physicochemical characteristics of the strongly coupled perylene-tetrapyrrole dyads render these architectures excellent candidates for light-harvesting materials with significant, even panchromatic, near-ultraviolet to near-infrared absorption.

Topics: Electrons; Oxidation-Reduction; Perylene; Porphyrins; Quantum Theory

Design, synthesis, and optical properties of a series of novel chlorin-bacteriochlorin energy transfer dyads are described. Each dyad is composed of a common red-absorbing (645-646 nm) chlorin, as an energy donor, and a different near-IR emitting bacteriochlorin, as an energy acceptor. Each bacteriochlorin acceptor is equipped with a different set of auxochromes, so that each of them emits at a different wavelength. Dyads exhibit an efficient energy transfer (≥0.77) even for chlorin-bacteriochlorin pairs with large (up to 122 nm) separation between donor emission and acceptor absorption. Excitation of the chlorin donor results in relatively strong emission of the bacteriochlorin acceptor, with a quantum yield Φf range of 0.155-0.23 in toluene and 0.12-0.185 in DMF. The narrow, tunable emission band of bacteriochlorins enables the selection of a series of three dyads with well-resolved emissions at 732, 760, and 788 nm, and common excitation at 645 nm. Selected dyads have been also converted into bioconjugatable N-succinamide ester derivatives. The optical properties of the described dyads make them promising candidates for development of a family of near-IR fluorophores for simultaneous imaging of multiple targets, where the whole set of fluorophores can be excited with the common wavelength, and fluorescence from each can be independently detected.

Topics: Energy Transfer; Fluorescent Dyes; Molecular Structure; Photochemistry; Porphyrins; Spectroscopy, Near-Infrared

The decay channels of the singlet excited states of halogenated sulfonamide tetraphenylporphyrins, chlorins and bacteriochlorins were fully characterized. It was found that the radiative rates and the internal conversion rates of the bacteriochlorins are lower than expected from the Strickler-Berg equation and from the energy-gap law, respectively. It is concluded that this family of bacteriochlorins can combine long-lived singlet states with photostability, which are desired properties to harvest near-infrared light.

Topics: Infrared Rays; Light; Methanol; Porphyrins; Quantum Theory; Temperature

Self-aggregates of a synthetic zinc porphyrin worked as a light absorber and photoexcited energy donor, transferred the collected energy to a small amount of 3-acetyl-(bacterio)chlorin monomer, and induced near-infrared fluorescence from the acceptors in aqueous micellar solution. These artificial supramolecular systems are novel models of the main light-harvesting antennas of green photosynthetic bacteria, chlorosomes.

Topics: Bacteria; Energy Transfer; Light-Harvesting Protein Complexes; Metalloporphyrins; Models, Biological; Porphyrins; Spectrometry, Fluorescence

Alkyl-Grignard addition to meso-tetraphenylporpholactone generates monoalkyl- and gem-bis-alkyloxazolochlorins. Together with compounds made by further synthetic manipulations of these derivatives, a series of chlorin-type chromophores with modulated optical properties is generated. Furthermore, their OsO(4)-mediated dihydroxylations and subsequent functional group transformations generate a family of bacteriochlorins that possess substituent-dependent optical properties. Thus, the formal replacement of a pyrrolidine moiety in chlorins and bacteriochlorins by variously substituted oxazoles is a flexible methodology to generate novel and stable chromophores that are tunable over a considerable range of the optical spectrum.

Topics: Alkylation; Molecular Structure; Oxazoles; Porphyrins

Demetalation of three synthetic zinc cyclic tetrapyrroles that possess identical peripheral substituents, zinc methyl bacteriopyropheophorbide a (zinc bacteriochlorin 1), zinc methyl 3-devinyl-3-acetyl-pyropheophorbide a (zinc chlorin 2), and zinc methyl 3-devinyl-3-acetyl-protopyropheophorbide a (zinc porphyrin 3), was kinetically analyzed under acidic conditions to examine the effects of macrocyclic structures on demetalation without peripheral substitution effects. Zinc bacteriochlorin 1 exhibited much slower demetalation kinetics than zinc chlorin 2 and zinc porphyrin 3. These results indicate that the bacteriochlorin skeleton provides significant resistance to the removal of the central metal from the tetrapyrrole ligand. Comparison of demetalation kinetics of 3-acetyl zinc complexes 2 and 3 with that of 3-vinyl zinc complexes under the same reaction condition demonstrated that the relative ratio (5.0 × 10(-2)) of the demetalation rate constant of the 3-acetyl zinc chlorin 2 to that of the corresponding 3-vinyl zinc chlorin 4 resembled the case of the 3-acetyl zinc porphyrin 3 to the 3-vinyl zinc porphyrin 5 (the relative ratio was 6.8 × 10(-2)). These suggest that the electron-withdrawing 3-acetyl group slows down the demetalation from the tetrapyrrole ligands more than the 3-vinyl group and that the 3-acetyl effect is analogous in both chlorin and porphyrin π-systems.

Topics: Chlorophyll; Kinetics; Porphyrins; Tetrapyrroles; Zinc

The refined syntheses, modification, and first X-ray structural characterization of meso-tetraarylporphyrin-derived beta-tetraolbacteriochlorins are described. These investigations assign the relative stereochemistry of their two isomers (both cis-vic-diol pairs on the same or opposite sides of the porphyrin plane), an assignment that could not be provided by NMR, UV-vis or fluorescence spectroscopy, or mass spectrometry. Moreover, the first crystal structures of a 2-hydroxychlorin and a 2,3-dihydroxychlorin, as its dimethylether, are reported. Dihydroxylation and diimide reduction of the dimethoxychlorin result in the formation of stable mixed-functionality bacteriochlorins. The photophysical properties (UV-vis absorption and fluorescence emission) of all chromophores are contrasted against each other, delineating the electronic effects of diol substitution and conformational modulation. Lastly, the acid-induced dehydration/demethoxylation of the tetraol-, dioldimethoxy-, and tetramethoxybacteriochlorins to provide chlorins is delineated.

Topics: Crystallography, X-Ray; Isomerism; Magnetic Resonance Spectroscopy; Mass Spectrometry; Models, Molecular; Porphyrins; Protons; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet

Chlorin and bacteriochlorin derivatives of 5,10,15,20-tetrakis(2-chloro-5-sulfophenyl)porphyrin have intense absorptions in the phototherapeutic window, high water solubility, high photostability, low fluorescence quantum yield, long triplet lifetimes, and high singlet oxygen quantum yields. Biological studies revealed their negligible dark cytotoxicity, yet significant photodynamic effect against A549 (human lung adenocarcinoma), MCF7 (human breast carcinoma) and SK-MEL-188 (human melanoma) cell lines upon red light irradiation (cutoff λ<600 nm) at low light doses. Time-dependent cellular accumulation of the chlorinated sulfonated chlorin reached a plateau at 2 h, as previously observed for the related porphyrin. However, the optimal incubation time for the bacteriochlorin derivative was significantly longer (12 h). The spectroscopic, photophysical, and biological properties of the compounds are discussed in relevance to their PDT activity, leading to the conclusion that the bacteriochlorin derivative is a promising candidate for future in vivo experiments.

Topics: Cell Line, Tumor; Halogenation; Humans; Neoplasms; Photochemotherapy; Photosensitizing Agents; Porphyrins; Spectrometry, Fluorescence; Water

The facile synthesis and photophysical properties of three nonhydrolyzable thioglycosylated porphyrinoids are reported. Starting from meso-perfluorophenylporphyrin, the nonhydrolyzable thioglycosylated porphyrin (PGlc₄), chlorin (CGlc₄), isobacteriochlorin (IGlc₄), and bacteriochlorin (BGlc₄) can be made in 2-3 steps. The ability to append a wide range of targeting agents onto the perfluorophenyl moieties, the chemical stability, and the ability to fine-tune the photophysical properties of the chromophores make this a suitable platform for development of biochemical tags, diagnostics, or as photodynamic therapeutic agents. Compared to the porphyrin in phosphate buffered saline, CGlc₄ has a markedly greater absorbance of red light near 650 nm and a 6-fold increase in fluorescence quantum yield, whereas IGlc₄ has broad Q-bands and a 12-fold increase in fluorescence quantum yield. BGlc₄ has a similar fluorescence quantum yield to PGlc₄ (<10%), but the lowest-energy absorption/emission peaks of BGlc₄ are considerably red-shifted to near 730 nm with a nearly 50-fold greater absorbance, which may allow this conjugate to be an effective PDT agent. The uptake of CGlc₄, IGlc₄, and BGlc₄ derivatives into cells such as human breast cancer cells MDA-MB-231 and K:Molv NIH 3T3 mouse fibroblast cells can be observed at nanomolar concentrations. Photobleaching under these conditions is minimal.

Topics: Animals; Cell Line, Tumor; Fluorescence; Humans; Mice; Molecular Imaging; Molecular Structure; NIH 3T3 Cells; Photochemistry; Porphyrins; Stereoisomerism; Sulfhydryl Compounds

Conjugates of bacteriochlorin p and chlorin e(6) with cobalt bis(dicarbollide) anion [3,3'-Co(1,2-C(2)B(9)H(11))(2)](-) were synthesized using different synthetic approaches. The boronated bacteriochlorin p was prepared by reaction of bacteriochlorin N-amino cycloimide with, bis(dicarbollide)-based carboxylic acid. The boronated chlorin e(6) conjugates were obtained by both "click reaction" of containing alkyne group chlorine with azide derivative of cobaltacarborane and reaction of chorin-based amines with cyclic oxonium derivative of cobalt bis(dicarbollide).

Topics: Boron Compounds; Boron Neutron Capture Therapy; Humans; Molecular Structure; Neoplasms; Photochemotherapy; Porphyrins; Radiation-Sensitizing Agents

Next-generation photodynamic therapy agents based upon the conjugation of multiple photosensitizers to a targeting backbone will allow for more efficacious light-based therapies. To this end, we have developed glucose-modified chlorins and bacteriochlorins featuring a reactive carboxylic acid linker for conjugation to targeting moieties. The photosensitizers were synthesized in relatively high yields from meso-tetra(p-aminophenyl)porphyrin, and resulted in neutral, hydrophilic chromophores with superb absorption profiles in the far-red and near-infrared portions of the electromagnetic spectrum. In addition, conjugation of these photosensitizers to a model nanoscaffold (crosslinked dextran-coated nanoparticles) demonstrated that the inclusion of hydrophilic sugar moieties increased the number of dyes that can be loaded while maintaining suspension stability. The described compounds are expected to be particularly useful in the synthesis of a number of targeted nanotherapeutic systems.

Topics: Cross-Linking Reagents; Glucose; Photochemotherapy; Photosensitizing Agents; Porphyrins; Static Electricity; Structure-Activity Relationship

The oxidation of bacteriopyropheophorbide with ferric chloride hexahydrate or its anhydrous form produced the ring-D oxidized (ring-B reduced) chlorin in >95% yield. Replacing the five-member isocyclic ring in bacteriopyropheophorbide- a with a fused six-member N-butylimide ring system made no difference in regioselective oxidation, and the corresponding ring-B reduced chlorin was isolated in almost quantitative yield. When the oxidant was replaced by 2,3-dichloro-5,6-dicyano-p-benzoquinone, which is frequently used at the oxidizing stage of the porphyrin synthesis, the ring-B oxidized (ring-D reduced) chlorins were obtained. With both ring-B reduced and ring-D reduced chlorins in hand, their photophysical and electrochemical properties were examined and compared for the first time. The ring-B reduced chlorine 20, with a fused six-member N-butylimide ring, exhibits the most red-shifted absorption band (at lambda(max) = 746 nm), the lowest fluorescence quantum yield (4.5%), and the largest quantum yield of singlet oxygen formation (67%) among the reduced ring-B and ring-D chlorins investigated in this study. Measurements of the one-electron oxidation and reduction potentials show that compound 20 is also the easiest to oxidize among the examined compounds and the third easiest to reduce. In addition, the 1.62 eV HOMO-LUMO gap of 20 is the smallest of the examined compounds, and this agrees with values calculated using the DFT method. Spectroelectrochemical measurements afforded UV-visible absorption spectra for both the radical cations and radical anions of the examined chlorins. The ring-B reduced compound 20, with a fused six-member N-butylimide ring, is regarded as the most promising candidate in this study for photodynamic therapy because it has the longest wavelength absorption and the largest quantum yield of singlet oxygen formation among the compounds investigated.

Topics: Bacteriochlorophyll A; Chlorides; Circular Dichroism; Computer Simulation; Electrochemistry; Ferric Compounds; Imides; Magnetic Resonance Spectroscopy; Models, Chemical; Molecular Conformation; Oxidation-Reduction; Photochemistry; Porphyrins; Quantum Theory; Reference Standards; Singlet Oxygen; Spectrometry, Fluorescence; Stereoisomerism

Electronic absorption spectra of six porphyrin-like photosensitizers, porphyrin, chlorin, bacteriochlorin, pheophytin a, porphyrazin, and texaphyrin, have been calculated within the time-dependent DFT framework (TDDFT) in conjunction with the PBE0 hybrid functional. Energetic and orbital aspects are discussed by comparing systems together so as to assess the best molecules for photodynamic therapy applications. Excitation energies and oscillator strengths are found to be in good agreement with both experimental data and previous theoretical works. In particular, whereas significant discrepancies (0.3 eV) appear for Qx bands, results become more reliable as wavelengths decrease. To elucidate the effect of the local environment, we have taken into account solvation either with explicit water molecules interacting via hydrogen bonds with the system or with a continuum model (C-PCM). The supramolecular approach does not affect spectra, while using C-PCM improves Qx and B band values and strengthens intensities significantly. In both gaseous and aqueous phases, texaphyrin, pheophytin a, and bacteriochlorin Qx bands are found in the 600-800 nm range as expected by experimental works. These data are particularly interesting in the perspective of systematic studies of other photosensitizers and should make experimentalists' works easier.

Topics: Energy Transfer; Hydrogen Bonding; Molecular Conformation; Pheophytins; Photochemotherapy; Photosensitizing Agents; Porphyrins; Spectrum Analysis; Time Factors

Allomerization of bacteriochlorophyll a (Bchl a) was studied under various reaction conditions. Bchl a on stirring with KOH/propanol produced an "unstable bacteriochlorin", which decomposed in acidic conditions to give a complex mixture containing bacteriopurpurin a as a principal component. The yields of other compounds varied and were found to be dependent on reaction condition. The structures of the isolated porphyrins, chlorins, and bacteriochlorins, related to Bchl a, were assigned on the basis of 1D, 2D NMR (ROESY), and mass spectroscopy analyses. The presence of fused anhydride rings in porphyrin, chlorin, and bacterichlorin systems showed a significant influence on their optical properties. Compared to bacteriochlorophyll a and bacteriopheophytin, the related structurally modified analogues, e.g., the bacteriopurpurin a, 13(1)/15(1)-N-alkyl isoimide, and the imide analogues were found to be more stable with a significant difference in spectroscopic properties. Bacteriochlorins containing anhydride, imide, or isoimide cyclic rings demonstrated a significant bathochromic shift of their Q bands in their electronic absorption spectra. Under basic conditions the formation of the 12-hydroxymethyl, 12-formyl, and 12-methylene analogues as byproducts from the 12-methyl-bacteriopurpurin-N-hexylimide could be due to subsequent oxidation of the vinylogous enolate intermediates. To investigate the effect of the central metal in the electronic spectra, the stable bacteriopurpurin-18-N-hexylimide was converted to a series of metal complexes [Zn(II), Cd(II), and Pd(II)] by following the direct or transmetalation approaches. Compared to the free-base analogue, these complexes showed a remarkable shift in their electronic absorption spectra.

Topics: Anhydrides; Anthraquinones; Bacteriochlorophyll A; Imides; Mass Spectrometry; Organometallic Compounds; Porphyrins

The efficiencies of organic solar cells that incorporate light-harvesting arrays of organic pigments were calculated under 1 sun of air mass 1.5 solar irradiation. In one set of calculations, photocurrent efficiencies were evaluated for porphyrin, phthalocyanine, chlorin, bacteriochlorin, and porphyrin-bis(perylene) pigment arrays of different length and packing densities under the assumption that each solar photon absorbed quantitatively yielded one electron in the external circuit. In another more realistic set of calculations, solar conversion efficiencies were evaluated for arrays comprising porphyrins or porphyrin-(perylene)2 units taking into account competitive excited-state relaxation pathways. A system of coupled differential equations for all reactions in the arrays was solved on the basis of previously published rate constants for (1) energy transfer between the perylene and porphyrin pigments, (2) excited-state relaxation of the perylene and porphyrin pigments, and (3) excited-state electron injection into the semiconductor. This formal analysis enables determination of the optimal number of pigments in an array for solar-to-electrical energy conversion. The optimal number of pigments depends on the molar absorption coefficient and the density at which the arrays can be packed on an electrode surface. Taken together, the ability to employ fundamental photophysical, kinetic, and structural parameters of modular molecular architectures in assessments of the efficiency of solar-to-electrical energy conversion should facilitate the design of molecular-based solar cells.

Topics: Electrons; Energy Transfer; Indoles; Isoindoles; Kinetics; Light; Metalloporphyrins; Models, Chemical; Molecular Structure; Perylene; Photochemistry; Porphyrins; Semiconductors; Sensitivity and Specificity; Spectrum Analysis; Surface Properties

Metal-free tetraazachlorin (TAC), -bacteriochlorin (TAB), and -isobacteriochlorin (TAiB) were characterized by electronic absorption, magnetic circular dichroism (MCD), fluorescence, and time-resolved ESR (TR-ESR) spectroscopy, and by cyclic voltammetry. The results are compared with those of metal-free tetraazaporphyrin (TAP). The potential difference DeltaE between the first oxidation and reduction couples decreases in the order TAP>TAiB>TAC>TAB. The splitting of both the Q and Soret bands decreases in the order TAB>TAC>TAP>TAiB. Corresponding to the split absorption bands, MCD spectra show a minus-to-plus pattern with increasing energy in both the Q and Soret regions, which suggests that the energy difference between the HOMO and second HOMO is larger than that between the LUMO and second LUMO. These spectroscopic properties and redox potentials were reproduced by molecular orbital calculations using the ZINDO/S Hamiltonian. The fluorescence quantum yields of the reduced species are much smaller than that of TAP. The zero-field splitting (ZFS) parameters D and E of the excited triplet states (T1) of these species decrease and increase, respectively, on going from TAP to TAC and further to TAB. The D and E values of TAiB are larger than those of the other species. The results are supported by the absence of interaction between the spin over reduced pyrrole moieties of the HOMO and over the LUMO, and by calculations of ZFS under a half-point-charge approximation.

Topics: Chemical Phenomena; Chemistry, Physical; Electrochemistry; Electron Spin Resonance Spectroscopy; Oxidation-Reduction; Porphyrins