Single-Polymer–Single-Cargo Strategy Packages Hydrophobic Fluorophores in Aqueous Solution with Retention of Inherent Brightness

A strategy for encapsulating hydrophobic organic entities in aqueous solution has been developed through use of a self-assembling heterotelechelic amphiphilic random copolymer. The polymer (∼40 kDa), prepared by living radical polymerization, contains orthogonally reactive terminal groups and pendant hydrophobic (dodecyl), nonionic hydrophilic (PEG9), and ionic hydrophilic (sulfonate-terminated) groups. Covalent conjugation of a hydrophobic entity to the polymer terminus has been demonstrated for 8 classes of organic fluorophores. The resulting “pod-fluorophore” architecture is unimeric (∼15 nm in diameter) in aqueous solution with spectral features and fluorescence brightness resembling those of the benchmark fluorophore in organic solution. This strategy separates the functional design of the packaged molecular entity (“cargo”) from the often vexing challenge of water solubilization and in so doing creates a unitary (one-pod–one-cargo) platform architecture for potential applications in cytometry, biomedical imaging, environmental sensing, and supramolecular chemistry

Rational Syntheses of Cyclic Hexameric Porphyrin Arrays for Studies of Self-Assembling Light-Harvesting Systems

Two new cyclic hexameric arrays of porphyrins have been prepared in a rational, convergent manner. The porphyrins in each cyclic hexamer are joined by diphenylethyne linkers affording a wheel-like array with a diameter of ∼35 Å. One array is comprised of five zinc (Zn) porphyrins and one free base (Fb) porphyrin (cyclo-Zn5FbU) while the other is comprised of an alternating sequence of two Zn porphyrins and one Fb porphyrin (cyclo-Zn2FbZn2FbU). The prior synthesis employed a one-flask template-directed process and afforded alternating Zn and Fb porphyrins or all Zn porphyrins. More diverse metalation patterns are attractive for manipulating the flow of excited-state energy in the arrays. The rational synthesis of each array employed three Pd-mediated coupling reactions with four tetraarylporphyrin building blocks bearing diethynyl, diiodo, bromo/iodo, or iodo/ethynyl groups. The final ring closure yielding the cyclic hexamer was achieved by reaction of a porphyrin pentamer + porphyrin monomer or the joining of two porphyrin trimers. In the presence of a tripyridyl template, the yields of the 5 + 1 and 3 + 3 reactions ranged from 10 to 13%. The 5 + 1 reaction in the absence of the template proceeded in 3.5% yield, thereby establishing the structure-directed contribution to cyclic hexamer formation. The 3 + 3 route relied on successive ethyne + iodo/bromo coupling reactions. One template-directed route to cyclo-Zn2FbZn2FbU employed a magnesium porphyrin, affording cyclo-Zn2FbZn2MgU from which magnesium was selectively removed. The arrays exhibit absorption spectra that are nearly the sum of the spectra of the component parts, indicating weak electronic coupling. Fluorescence spectroscopy showed that the quantum yield of energy transfer in toluene at room temperature from the Zn porphyrins to the Fb porphyrin(s) was 60% in cyclo-Zn5FbU and 90% in cyclo-Zn2FbZn2FbU. Two dipyridyl-substituted porphyrins, a Zn tetraarylporphyrin and a Fb oxaporphyrin, have been synthesized for use as guests in the cyclic hexamers, affording self-assembled arrays for light-harvesting studies

Rational Synthesis of Meso-Substituted Porphyrins Bearing One Nitrogen Heterocyclic Group

Rational Synthesis of Meso-Substituted Porphyrins Bearing One Nitrogen Heterocyclic Grou

Construction of the Bacteriochlorin Macrocycle with Concomitant Nazarov Cyclization To Form the Annulated Isocyclic Ring: Analogues of Bacteriochlorophyll <i>a</i>

Bacteriochlorophylls contain a bacteriochlorin macrocycle bearing an annulated fifth ring. The fifth ring, termed the isocyclic ring or ring E, is equipped with 131-oxo and 132-carbomethoxy substituents. Herein, a general route to stable, synthetic bacteriochlorophyll analogues is described. Knoevenagel condensation (∼40 mM, rt, CH2Cl2, piperidine/AcOH/molecular sieves) of a dihydrodipyrrin–carboxaldehyde (AD half) and a dihydrodipyrrin substituted with a β-ketoester (BC half) forms a propenone bearing the two halves (a hydrobilin analogue). Subsequent treatment (0.2 mM) with acid (Yb­(OTf)3, CH3CN, 80 °C) promotes a double ring-closure process: (i) condensation between the α-position of pyrrole ring A and the α-acetal unit attached to pyrroline ring B forms the bacteriochlorin macrocycle, and (ii) Nazarov cyclization of the β-(propenoyl)-substituted ring C forms the isocyclic ring (E). Five new bacteriochlorins bearing various substituents (alkyl/alkyl, aryl, and alkyl/ester) at positions 2 and 3 (β-pyrrole sites, ring A) and 132 carboalkoxy groups (R = Me or Et) were constructed in 37–61% yield from the hydrobilin analogues. The BC half and AD half are available in five and eight steps, respectively, from the corresponding pyrrole-2-carboxaldehyde and unsaturated ketone. The bacteriochlorins exhibit absorption spectra typical of bacteriopheophytins (free base bacteriochlorophylls), with a strong near-infrared absorption band (707–751 nm)

Synthesis of Swallowtail-Substituted Multiporphyrin Rods

The availability of multiporphyrin arrays with defined architectures and good solubility in organic solvents is essential for a wide variety of physical studies. Herein the synthesis of linear multiporphyrin arrays (triads, tetrad, pentad) bearing solubilizing 7-tridecyl (swallowtail) groups is presented. The rodlike arrays are composed of zinc porphyrins at the termini and 1, 2, or 3 free base porphyrins at the core. The free base porphyrins in the tetrad and pentad are joined to each other via p-phenylene linkers whereas the zinc porphyrins in each array are attached to the core free base porphyrins via 1,4-diphenylethyne linkers. The arrays are designed for studies of interporphyrin electronic communication

Northern–Southern Route to Synthetic Bacteriochlorins

A new route to bacteriochlorins via Northern–Southern (N-S) self-condensation of a dihydrodipyrrin–acetal complements a prior Eastern–Western (E-W) route. Each bacteriochlorin was prepared in five steps from an α-halopyrrole and a 2,2-dimethylpent-4-ynoic acid. The first three steps follow Jacobi’s synthesis of dihydrodipyrrins: Pd-mediated coupling to form a lactone–pyrrole, Petasis reagent treatment for methenylation, and Paal–Knorr type ring closure to form the 1,2,2-trimethyl-substituted dihydrodipyrrin. Subsequent steps entail conversion of the 1-methyl group to the 1-(dimethoxymethyl) unit and acid-catalyzed self-condensation of the resulting dihydrodipyrrin–acetal. The essential differences between the N-S and E-W routes lie in (1) the location of the gem-dimethyl group (with respect to the 1-acetal unit) at the 2- versus 3-position in the dihydrodipyrrin–acetals, respectively, (2) the method of synthesis of the dihydrodipyrrins, and consequently (3) access to diverse substituted bacteriochlorins including those with substituents at the meso-positions. Ten new bacteriochlorins bearing 0–6 total aryl, alkyl, and carboethoxy substituents at the β-pyrrole and/or meso-positions have been prepared, with yields of macrocycle formation of up to 39%. Four single-crystal X-ray structures (two intermediates, two bacteriochlorins) were determined. The bacteriochlorins exhibit characteristic bacteriochlorophyll-like absorption spectra, including a Qy band in the region 713–760 nm

Efficient Synthesis of Light-Harvesting Arrays Composed of Eight Porphyrins and One Phthalocyanine

Effective light-harvesting arrays require multiple photoactive energy donors that funnel energy to an energy acceptor. Porphyrins and phthalocyanines are attractive components for light-harvesting arrays due to their strong absorption in the blue and red regions, respectively, and because energy transfer can occur from porphyrin to phthalocyanine regardless of their respective metalation states. Star-shaped light-harvesting arrays comprised of eight peripheral porphyrins and one core phthalocyanine have been prepared by a streamlined synthesis involving minimal reliance on protecting groups, a high degree of convergence, and facile chromatographic purification. The synthesis involves three distinct stages of complementary chemistries (porphyrin formation, Pd-mediated porphyrin dimer formation, phthalocyanine formation). Statistical reaction of p-iodobenzaldehyde, a phthalonitrile-linked benzaldehyde, and 5-mesityldipyrromethane afforded the desired trans-iodo/phthalonitrile-substituted porphyrin, which underwent Pd-mediated coupling with a monoethynyl porphyrin to give the porphyrin dimer bearing a phthalonitrile unit. Reaction of the dimer in 1-pentanol in the presence of MgCl2 and DBU for 48 h at 145 °C afforded the all-magnesium (porphyrin)8−phthalocyanine nonamer (MgP)8MgPc in 5.0% yield. The same reaction with lithium pentoxide in 1-pentanol for 2 h at 145 °C gave the all-free base nonamer (H2P)8H2Pc in 34% yield. The all-zinc nonamer (ZnP)8ZnPc was prepared by addition of zinc acetate at the end of the reaction. Similar treatment of a monomeric porphyrin−phthalonitrile afforded the pentameric (ZnP)4ZnPc in 58% yield. The (MgP)8MgPc was also obtained by magnesium insertion of (H2P)8H2Pc. The three nonamers were readily purified and are soluble in solvents such as toluene, THF, and CH2Cl2. Each nonamer absorbs strongly across the solar spectrum and exhibits efficient energy transfer from the porphyrins to the phthalocyanine

Rational Syntheses of Cyclic Hexameric Porphyrin Arrays for Studies of Self-Assembling Light-Harvesting Systems

Two new cyclic hexameric arrays of porphyrins have been prepared in a rational, convergent manner. The porphyrins in each cyclic hexamer are joined by diphenylethyne linkers affording a wheel-like array with a diameter of ∼35 Å. One array is comprised of five zinc (Zn) porphyrins and one free base (Fb) porphyrin (cyclo-Zn5FbU) while the other is comprised of an alternating sequence of two Zn porphyrins and one Fb porphyrin (cyclo-Zn2FbZn2FbU). The prior synthesis employed a one-flask template-directed process and afforded alternating Zn and Fb porphyrins or all Zn porphyrins. More diverse metalation patterns are attractive for manipulating the flow of excited-state energy in the arrays. The rational synthesis of each array employed three Pd-mediated coupling reactions with four tetraarylporphyrin building blocks bearing diethynyl, diiodo, bromo/iodo, or iodo/ethynyl groups. The final ring closure yielding the cyclic hexamer was achieved by reaction of a porphyrin pentamer + porphyrin monomer or the joining of two porphyrin trimers. In the presence of a tripyridyl template, the yields of the 5 + 1 and 3 + 3 reactions ranged from 10 to 13%. The 5 + 1 reaction in the absence of the template proceeded in 3.5% yield, thereby establishing the structure-directed contribution to cyclic hexamer formation. The 3 + 3 route relied on successive ethyne + iodo/bromo coupling reactions. One template-directed route to cyclo-Zn2FbZn2FbU employed a magnesium porphyrin, affording cyclo-Zn2FbZn2MgU from which magnesium was selectively removed. The arrays exhibit absorption spectra that are nearly the sum of the spectra of the component parts, indicating weak electronic coupling. Fluorescence spectroscopy showed that the quantum yield of energy transfer in toluene at room temperature from the Zn porphyrins to the Fb porphyrin(s) was 60% in cyclo-Zn5FbU and 90% in cyclo-Zn2FbZn2FbU. Two dipyridyl-substituted porphyrins, a Zn tetraarylporphyrin and a Fb oxaporphyrin, have been synthesized for use as guests in the cyclic hexamers, affording self-assembled arrays for light-harvesting studies

Rational Syntheses of Cyclic Hexameric Porphyrin Arrays for Studies of Self-Assembling Light-Harvesting Systems

Two new cyclic hexameric arrays of porphyrins have been prepared in a rational, convergent manner. The porphyrins in each cyclic hexamer are joined by diphenylethyne linkers affording a wheel-like array with a diameter of ∼35 Å. One array is comprised of five zinc (Zn) porphyrins and one free base (Fb) porphyrin (cyclo-Zn5FbU) while the other is comprised of an alternating sequence of two Zn porphyrins and one Fb porphyrin (cyclo-Zn2FbZn2FbU). The prior synthesis employed a one-flask template-directed process and afforded alternating Zn and Fb porphyrins or all Zn porphyrins. More diverse metalation patterns are attractive for manipulating the flow of excited-state energy in the arrays. The rational synthesis of each array employed three Pd-mediated coupling reactions with four tetraarylporphyrin building blocks bearing diethynyl, diiodo, bromo/iodo, or iodo/ethynyl groups. The final ring closure yielding the cyclic hexamer was achieved by reaction of a porphyrin pentamer + porphyrin monomer or the joining of two porphyrin trimers. In the presence of a tripyridyl template, the yields of the 5 + 1 and 3 + 3 reactions ranged from 10 to 13%. The 5 + 1 reaction in the absence of the template proceeded in 3.5% yield, thereby establishing the structure-directed contribution to cyclic hexamer formation. The 3 + 3 route relied on successive ethyne + iodo/bromo coupling reactions. One template-directed route to cyclo-Zn2FbZn2FbU employed a magnesium porphyrin, affording cyclo-Zn2FbZn2MgU from which magnesium was selectively removed. The arrays exhibit absorption spectra that are nearly the sum of the spectra of the component parts, indicating weak electronic coupling. Fluorescence spectroscopy showed that the quantum yield of energy transfer in toluene at room temperature from the Zn porphyrins to the Fb porphyrin(s) was 60% in cyclo-Zn5FbU and 90% in cyclo-Zn2FbZn2FbU. Two dipyridyl-substituted porphyrins, a Zn tetraarylporphyrin and a Fb oxaporphyrin, have been synthesized for use as guests in the cyclic hexamers, affording self-assembled arrays for light-harvesting studies

A <i>trans</i>-AB-Bacteriochlorin Building Block

Synthetic bacteriochlorins are of interest for fundamental studies in photochemistry because of their strong absorption in the near-infrared spectral region and close similarity with natural bacteriochlorophylls. A de novo route to 5-methoxybacteriochlorins entails self-condensation of a dihydrodipyrrin–acetal, which in turn is prepared from a 2-(2-nitroethyl)­pyrrole species and an α,β-unsaturated ketone–acetal (e.g., 1,1-dimethoxy-4-methylpent-3-en-2-one). Here, four new results are reported concerning the synthesis of substituted bacteriochlorins. First, a new, scalable route to 1,1-dimethoxy-4-methylpent-3-en-2-one removes a significant previous impediment to the overall route. Second, the new route was employed to gain access to new α,β-unsaturated ketones and corresponding dihydrodipyrrins bearing alternative substituents in place of the dimethoxy unit. Third, a dihydrodipyrrin bearing a 1,3-dioxolan-2-yl moiety afforded the bacteriochlorin (30% yield) containing a 2-hydroxyethoxy substituent at the 5-position. Fourth, subsequent bromination proceeded regioselectively at the 15-position to give a trans-(5,15)-AB-bacteriochlorin building block. The linear 5,15-substitution pattern is attractive for a number of molecular designs. The results taken together afford deeper understanding of the scope and limitations of the de novo route and also advance the capabilities for tailoring synthetic bacteriochlorins