Synthesis and electronic properties of regioisomerically pure oxochlorins

We describe a two-step conversion of C-alkylated zinc chlorins to zinc oxochlorins wherein the keto group is located in the reduced ring (17-position) of the macrocycle. The transformation proceeds by hydroxylation upon exposure to alumina followed by dehydrogenation with DDQ. The reactions are compatible with ethyne, iodo, ester, trimethylsilyl, and pentafluorophenyl groups. A route to a spirohexyl-substituted chlorin/oxochlorin has also been developed. Representative chlorins and oxochlorins were characterized by static and time-resolved absorption spectroscopy and fluorescence spectroscopy, resonance Raman spectroscopy, and electrochemistry. The fluorescence quantum yields of the zinc oxochlorins (Phi(f) = 0.030-0.047) or free base (Fb) oxochlorins (Phi(f) = 0.13-0.16) are comparable to those of zinc tetraphenylporphyrin (ZnTPP) or free base tetraphenylporphyrin (FbTPP), respectively. The excited-state lifetimes of the zinc oxochlorins (tau = 0.5-0.7 ns) are on average 4-fold lower than that of ZnTPP, and the lifetimes of the Fb oxochlorins (tau = 7.4-8.9 ns) are approximately 40% shorter than that of FbTPP. Time-resolved absorption spectroscopy of a zinc oxochlorin indicates the yield of intersystem crossing is >70%. Resonance Raman spectroscopy of copper oxochlorins show strong resonance enhancement of the keto group upon Soret excitation but not with Q(y)()-band excitation, which is attributed to the location of the keto group in the reduced ring (rather than in the isocyclic ring as occurs in chlorophylls). The one-electron oxidation potential of the zinc oxochlorins is shifted to more positive potentials by approximately 240 mV compared with that of the zinc chlorin. Collectively, the fluorescence yields, excited-state lifetimes, oxidation potentials, and various spectral characteristics of the chlorin and oxochlorin building blocks provide the foundation for studies of photochemical processes in larger architectures based on these chromophores.     

Sparsely substituted chlorins as core constructs in chlorophyll analogue chemistry. II. Derivatization

Stable chlorins bearing few or no substituents have been subjected to a variety of reactions including demetalation, magnesium insertion, oxochlorin formation, and bromination followed by Suzuki coupling. The kinetics of deuteration also have been determined for two oxochlorins and a series of chlorins bearing 0, 1, 2, or 3 meso-aryl substituents.     

Comparison of excited-state energy transfer in arrays of hydroporphyrins (chlorins, oxochlorins) versus porphyrins: rates, mechanisms, and design criteria

A set of chlorin-chlorin and oxochlorin-oxochlorin dyads has been prepared with components in the same or different metalation states. In each case a 4,4'-diphenylethyne linker spans the respective 10-position of each macrocycle. The dyads have been studied using static and time-resolved absorption and emission spectroscopy, resonance Raman spectroscopy, and electrochemical techniques. Excited-state energy transfer from a zinc chlorin to a free-base (Fb) chlorin occurs with a rate constant of (110 ps)(-1) and an efficiency of 93%; similar values of (140 ps)(-1) and 83% are found for the corresponding oxochlorin dyad. Energy transfer in both dyads is slower and less efficient than found previously for the analogous porphyrin dyad, which displays a rate of (24 ps)(-1) and a yield of 99%. The slower rates and diminished efficiencies in the ZnFb chlorin and oxochlorin dyads versus the ZnFb porphyrin dyad are attributed to substantially weaker linker-mediated through-bond (TB) electron-exchange coupling (as indicated by resonance Raman data). Although the through-space (TS, i.e., dipole-dipole) coupling in the ZnFb-chlorin and -oxochlorin dyads is enhanced relative to the ZnFb porphyrin dyad (as indicated by F?rster calculations), this enhancement is insufficient to compensate for the greatly diminished TB coupling. Taken together, the chlorin and oxochlorin dyads examined herein serve as benchmarks for elucidating the energy-transfer, electrochemical, and other properties of light-harvesting arrays containing multiple chlorins or oxochlorins.     

Rational synthesis of meso-substituted chlorin building blocks

Chlorins provide the basis for plant photosynthesis, but synthetic model systems have generally employed porphyrins as surrogates due to the unavailability of suitable chlorin building blocks. We have adapted a route pioneered by Battersby to gain access to chlorins that bear two meso substituents, a geminal dimethyl group to lock in the chlorin hydrogenation level, and no flanking meso and beta substituents. The synthesis involves convergent joining of an Eastern half and a Western half. A 3,3-dimethyl-2,3-dihydrodipyrrin (Western half) was synthesized in four steps from pyrrole-2-carboxaldehyde. A bromodipyrromethane carbinol (Eastern half) was prepared by sequential acylation and bromination of a 5-substituted dipyrromethane followed by reduction. Chlorin formation is achieved by a two-flask process of acid-catalyzed condensation followed by metal-mediated oxidative cyclization. The latter reaction has heretofore been performed with copper templates. Investigation of conditions for this multistep process led to copper-free conditions (zinc acetate, AgIO(3), and piperidine in toluene at 80 degrees C for 2 h). The zinc chlorin was obtained in yields of approximately 10% and could be easily demetalated to give the corresponding free base chlorin. The synthetic process is compatible with a range of meso substituents (p-tolyl, mesityl, pentafluorophenyl, 4-[2-(trimethylsilyl)ethynyl]phenyl, 4-iodophenyl). Altogether four free base and four zinc chlorins have been prepared. The chlorins exhibit typical absorption spectra, fluorescence spectra, and fluorescence quantum yields. The ease of synthetic access, presence of appropriate substituents, and characteristic spectral features make these types of chlorins well suited for incorporation in synthetic model systems.     

Reductive metalation of 1,2-diaryl-substituted ethenes: synthetic applications

Reduction of 1,2-diaryl-substituted ethenes with Na metal in dry THF allowed easy access to a variety of 1,2-diaryl-1,2-disodiumethanes. These diorganometallic intermediates were elaborated into the corresponding 1,2-diarylethanes (aqueous work up), or cycloalkylated with 1,3-dichloropropanes. The last reaction led to a highly diastereoselective synthesis of trans-1,2-diaryl-substituted cyclopentanes.     

Synthesis of phenylethyne-linked porphyrin dyads

Four new porphyrin dyads have been prepared for studies in artificial photosynthesis. The two porphyrins are joined at the meso positions via a phenylethyne linker and are present in zinc/zinc or zinc/free base metalation states. The porphyrin bearing the ethynyl unit incorporates zero, one, or two pentafluorophenyl groups at non-linking meso positions for tuning the porphyrin redox potentials. The synthetic approach entailed Pd-mediated coupling of porphyrin building blocks that bear a single ethynylphenyl or bromo/iodo substituent.     

Effects of substituents on synthetic analogs of chlorophylls. Part 1: Synthesis, vibrational properties and excited-state decay characteristics

Understanding the effects of substituents on the spectra of chlorins is essential for a wide variety of applications. Recent developments in synthetic methodology have made possible systematic studies of the properties of the chlorin macrocycle as a function of diverse types and patterns of substituents. In this paper, the spectral, vibrational and excited-state decay characteristics are examined for a set of synthetic chlorins. The chlorins bear substituents at the 5,10,15 (meso) positions or the 3,13 (beta) positions (plus 10-mesityl in a series of compounds) and include 24 zinc chlorins, 18 free base (Fb) analogs and one Fb or zinc oxophorbine. The oxophorbine contains the keto-bearing isocyclic ring present in the natural photosynthetic pigments (e.g. chlorophyll a). The substituents cause no significant perturbation to the structure of the chlorin macrocycle, as evidenced by the vibrational properties investigated using resonance Raman spectroscopy. In contrast, the fluorescence properties are significantly altered due to the electronic effects of substituents. For example, the fluorescence wavelength maximum, quantum yield and lifetime for a zinc chlorin bearing 3,13-diacetyl and 10-mesityl groups (662 nm, 0.28, 6.0 ns) differ substantially from those of the parent unsubstituted chlorin (602 nm, 0.062, 1.7 ns). Each of these properties of the lowest singlet excited state can be progressively stepped between these two extremes by incorporating different substituents. These perturbations are associated with significant changes in the rate constants of the decay pathways of the lowest excited singlet state. In this regard, the zinc chlorins with the red-most fluorescence also have the greatest radiative decay rate constant and are expected to have the fastest nonradiative internal conversion to the ground state. Nonetheless, these complexes have the longest singlet excited-state lifetime. The Fb chlorins bearing the same substituents exhibit similar fluorescence properties. Such combinations of factors render the chlorins suitable for a range of applications that require tunable coverage of the solar spectrum, long-lived excited states and red-region fluorescence.     

Synthesis and excited-state photodynamics of a chlorin-bacteriochlorin dyad--through-space versus through-bond energy transfer in tetrapyrrole arrays.

Understanding energy transfer among hydroporphyrins is of fundamental interest and essential for a wide variety of photochemical applications. Toward this goal, a synthetic free base ethynylphenylchlorin has been coupled with a synthetic free base bromobacteriochlorin to give a phenylethyne-linked chlorin-bacteriochlorin dyad (FbC-pe-FbB). The chlorin and bacteriochlorin are each stable toward adventitious oxidation because of the presence of a geminal dimethyl group in each reduced pyrrole ring. A combination of static and transient optical spectroscopic studies indicate that excitation into the Qy band of the chlorin constituent (675 nm) of FbC-pe-FbB in toluene results in rapid energy transfer to the bacteriochlorin constituent with a rate of approximately (5 ps)(-1) and efficiency of >99%. The excited bacteriochlorin resulting from the energy-transfer process in FbC-pe-FbB has essentially the same fluorescence characteristics as an isolated monomeric reference compound, namely a narrow (12 nm fwhm) fluorescence emission band at 760 nm and a long-lived (5.4 ns) Qy excited state that exhibits a significant fluorescence quantum yield (Phif=0.19). F?rster calculations are consistent with energy transfer in FbC-pe-FbB occurring predominantly by a through-space mechanism. The energy-transfer characteristics of FbC-pe-FbB are compared with those previously obtained for analogous phenylethyne-linked dyads consisting of two porphyrins or two oxochlorins. The comparisons among the sets of dyads are facilitated by density functional theory calculations that elucidate the molecular-orbital characteristics of the energy donor and acceptor constituents. The electron-density distributions in the frontier molecular orbitals provide insights into the through-bond electronic interactions that can also contribute to the energy-transfer process in the different types of dyads.     

One-pot oxidation and bromination of 3,4-diaryl-2,5-dihydrothiophenes using Br2: synthesis and application of 3,4-diaryl-2,5-dibromothiophenes

A class of 3,4-diaryl-2,5-dibromothiophenes (1b-5b) was synthesized by a one-pot reaction of 3,4-diaryl-2,5-dihydrothiophenes with Br2 reagent in excellent yield (83-92%). It was found that Br2 performed a double function (oxidation and bromination) during the conversion of 3,4-diaryl-2,5-dihydrothiophenes to 3,4-diaryl-2,5-dibromothiophenes. The application of 3,4-diaryl-2,5-dibromothiophenes used as building blocks was also investigated. Employing 3,4-diphenyl-2,5-dibromothiophene (1b) as a template, a class of 2,3,4,5-tetraarylthiophenes was prepared by the Suzuki coupling reaction. This provided a new and simple approach to the preparation of 2,3,4,5-tetraarylthiophenes.     

Examination of chlorin-bacteriochlorin energy-transfer dyads as prototypes for near-infrared molecular imaging probes

Abstract New classes of synthetic chlorin and bacteriochlorin macrocycles are characterized by narrow spectral widths, tunable absorption and fluorescence features across the red and near-infrared (NIR) regions, tunable excited-state lifetimes (<1 to >10 ns) and chemical stability. Such properties make dyad constructs based on synthetic chlorin and bacteriochlorin units intriguing candidates for the development of NIR molecular imaging probes. In this study, two such dyads (FbC-FbB and ZnC-FbB) were investigated. The dyads contain either a free base (Fb) or zinc (Zn) chlorin (C) as the energy donor and a free base bacteriochlorin (B) as the energy acceptor. In both constructs, energy transfer from the chlorin to bacteriochlorin occurs with a rate constant of approximately (5 ps)(-1) and a yield of >99%. Thus, each dyad effectively behaves as a single chromophore with an exceptionally large Stokes shift (85 nm for FbC-FbB and 110 nm for ZnC-FbB) between the red-region absorption of the chlorin and the NIR fluorescence of the bacteriochlorin (lambda(f) = 760 nm, Phi(f) = 0.19, tau approximately 5.5 ns in toluene). The long-wavelength transitions (absorption, emission) of each constituent of each dyad exhibit narrow (相似文献   

An efficient PIFA-mediated synthesis of a directly linked zinc chlorin dimer via regioselective oxidative coupling

The synthesis of a directly linked zinc chlorin dimer was first achieved by a facile and efficient oxidative coupling of zinc chlorin monomers with phenyliodine bis(trifluoroacetate) (PIFA). The reaction shows high regioselectivity at the 20-position near the hydrogenated pyrrole ring producing selective dichlorin in 74% yield.     

Effects of Substituents on Synthetic Analogs of Chlorophylls. Part 4: How Formyl Group Location Dictates the Spectral Properties of Chlorophylls b,d and f

Photosynthetic organisms are adapted to light characteristics in their habitat in part via the spectral characteristics of the associated chlorophyll pigments, which differ in the position of a formyl group around the chlorin macrocycle (chlorophylls b, d, f) or no formyl group (chlorophyll a). To probe the origin of this spectral tuning, the photophysical and electronic structural properties of a new set of synthetic chlorins are reported. The zinc and free base chlorins have a formyl group at either the 2‐ or 3‐position. The four compounds have fluorescence yields in the range 0.19–0.28 and singlet excited‐state lifetimes of ca 4 ns for zinc chelates and ca 8 ns for the free base forms. The photophysical properties of the 2‐ and 3‐formyl zinc chlorins are similar to those observed previously for 13‐formyl or 3,13‐diformyl chlorins, but differ markedly from those for 7‐formyl analogs. Molecular‐orbital characteristics obtained from density functional theory (DFT) calculations were used as input to spectral simulations employing the four‐orbital model. The analysis has uncovered the key changes in electronic structure engendered by the presence/location of a formyl group at various macrocycle positions, which is relevant to understanding the distinct spectral properties of the natural chlorophylls a, b, d and f.     

Rational synthesis of beta-substituted chlorin building blocks

Chlorins bearing synthetic handles at specific sites about the perimeter of the macrocycle constitute valuable building blocks. We previously developed methodology for preparing meso-substituted chlorin building blocks and now present methodology for preparing several complementary beta-substituted chlorin building blocks. The chlorins bear one or two beta substituents, one meso substituent, a geminal dimethyl group to lock in the chlorin hydrogenation level, and no flanking meso and beta substituents. The synthesis involves convergent joining of an Eastern half and a Western half. New routes have been developed to two beta-substituted bromo-dipyrromethane monocarbinols (Eastern halves). A new beta-substituted Western half was prepared following the method for preparing an unsubstituted Western half (3,3-dimethyl-2,3-dihydrodipyrrin). Chlorin formation is achieved by a two-flask process of acid-catalyzed condensation followed by metal-mediated oxidative cyclization. beta-Substituted chlorins have been prepared in 18-24% yield bearing a 4-iodophenyl group at the 8-position, a 4-iodophenyl group or a 4-[2-(trimethylsilyl)ethynyl]phenyl group at the 12-position, and a 4-iodophenyl group and a 4-[2-(trimethylsilyl)ethynyl]phenyl group at diametrically opposed beta-positions (2, 12). The latter building block makes possible the stepwise construction of linear multi-chlorin architectures. The chlorins exhibit typical absorption and fluorescence spectra. A systematic shift in the absorption maximum (637-655 nm for the free base chlorins, 606-628 nm for the zinc chlorins) and intensity of the chlorin Q(y)() band (epsilon up to 79 000 M(-)(1) cm(-)(1)) is observed depending on the location of the substituents. The characteristic spectral features and location of substituents in defined positions make these chlorins well suited for a variety of applications in biomimetic and materials chemistry.     

Tailoring a bacteriochlorin building block with cationic, amphipathic, or lipophilic substituents

Bacteriochlorins are attractive candidates for photodynamic therapy (PDT) of diverse medical indications owing to their strong absorption in the near-infrared (NIR) region, but their use has been stymied by lack of access to stable, synthetically malleable molecules. To overcome these limitations, a synthetic free base 3,13-dibromobacteriochlorin (BC-Br(3)Br(13)) has been exploited as a building block in the synthesis of diverse bacteriochlorins via Pd-mediated coupling reactions (Sonogashira, Suzuki, and reductive carbonylation). Each bacteriochlorin is stable to adventitious dehydrogenation by virtue of the presence of a geminal dimethyl group in each pyrroline ring. The target bacteriochlorins bear cationic, lipophilic, or amphipathic substituents at the 3- and 13- (beta-pyrrolic) positions. A dicarboxybacteriochlorin was converted to amide derivatives via the intermediate diacid chloride. A diformylbacteriochlorin was subjected to reductive amination to give aminomethyl derivatives. A set of 3,5-disubstituted aryl groups bearing lipophilic or amphipathic groups was introduced via Suzuki coupling. Altogether 22 free base bacteriochlorins have been prepared. Eight aminoalkylbacteriochlorins were quaternized with methyl iodide at two or four amine sites per molecule, which resulted in water solubility. Each bacteriochlorin exhibits a Q(y) absorption band in the range of 720-772 nm. The ability to introduce a wide variety of peripheral functional groups makes these bacteriochlorins attractive candidates for diverse applications in photomedicine including PDT in the NIR region.     

Sparsely substituted chlorins as core constructs in chlorophyll analogue chemistry. III. Spectral and structural properties

The availability of stable chlorins bearing few or no substituents has enabled a variety of fundamental studies. The studies described herein report absorption spectra of diverse chlorins, comparative NMR features of chlorins bearing 0-3 meso-aryl substituents, and X-ray structures of the fully unsubstituted chlorin and the oxochlorin.     

Chemistry of 1,5-diketones: II. Specificity of transformations of polycyclic 1,5-diketones in acid media

2-(1,3-Diaryl-3-oxopropyl)cyclohexan-1-ones underwent carbo-and heterocyclization in a mixture of acetic acid with acetic anhydride in the presence of perchloric acid. The transformation of 2-(1,3-diaryl-3-oxopropyl)cyclohexan-1-ones into 2,4-diaryl-5,6,7,8-tetrahydrochromenylium salts was shown to involve intermediate 2,4-diarylbicyclo[3.3.1]non-2-en-9-ones. The structure of 2,4-diaryl-substituted bicyclo[3.3.1]non-2-en-9-ones and products of their reactions with halogens and hydroxylamine hydrochloride was confirmed by ¹H and ¹³C NMR spectroscopy.     

Self-assembled zinc chlorin rod antennae powered by peripheral light-harvesting chromophores

The multichromophoric dyads 1, 2 and triad 3 have been synthesized by coupling of the appropriately functionalized chlorin derivative with naphthalene diimide dyes through esterification, and subsequent metalation of the chlorin center with zinc acetate. The self-assembly properties of naphthalene diimide (NDI)-zinc chlorin (ZnChl) dyads 1, 2 and triad 3 have been studied in nonpolar, aprotic solvents by UV-vis, CD, and steady-state emission spectroscopy, revealing formation of rod-like structures by noncovalent interactions of zinc chlorin units, while the appended naphthalene diimide dyes do not aggregate at the periphery of the rod antennae. In all these systems, photoexcitation of the enveloping naphthalene diimides at 540 and 620 nm, respectively, leads to highly efficient energy-transfer processes (FRET; phiET > or = 0.99) to the inner zinc chlorin backbone, as explored by time-resolved fluorescence spectroscopy on the picosecond time scale. The efficiencies of zinc chlorin rod aggregates for the harvesting of solar light are markedly increased from 26% for dyad 2 up to 63% for triad 3, compared to the LH capacity of the monochromophoric aggregates of model system ZnChl 6a. Thus, with the self-assembled zinc chlorin rod antenna based on triad 3, a highly efficient artificial LH system has been achieved.     

An investigation of the bromination of 1,4-dihydropyridine rings

Conditions for bromination at the C3 and C5 positions of a 1,4-dihydropyridine (DHP) were investigated. The effect of base concentration, base type, reaction temperature, and solvent were examined. DHP derivatives with ester and amide moieties were synthesized and brominated. The bromine atoms can be replaced by other substituents, utilizing Suzuki cross coupling.     

A structural isomer of nonaromatic porphyrin: preparation of 20pi-conjugated porphycene based on electronic perturbation

A porphycene having four CF3 groups at the beta-pyrrolic positions affords a stable 20pi-conjugated form in the presence of a 2H+-2e- donor due to the high redox potential of the tetrapyrrole ring framework. No visible band in the UV-vis spectrum and the highly ruffled structure determined by X-ray crystallography support its nonaromatic character. The ethylene bridge moiety in the 20pi-conjugated framework displayed the olefinic reactivities.     

Effect of pyridine on the reaction of “spanned” zinc porphyrin with organic peroxides

The reaction of “spanned” zinc porphyrin with organic peroxides in the presence of pyridine at 298 K was studied. The kinetic characteristics of the reaction were obtained. The presence of pyridine favors the formation of the zinc chlorin complex. The nature of the nitrogen base affects the character and rate of the reactions of the zinc porphyrin with peroxide. The structures of the sterically strained metal porphyrin and of the chlorin complex formed in the reaction were optimized by PM3 calculations. As follows from the geometric structure of the macrocyclic compounds, the deformations of the macroring enhance in going from zinc porphyrin to zinc chlorin.