Porphyrin dimers linked in the meso-positions by bridges containing alkynes conjugated with the porphyrin π-systems display highly perturbed electronic absorption spectra. We have prepared a series of such dimers using meso-ethynyl nickel(II) octaethylporphyrin as the primary building block. The bridging units include diethynylbenzenes, 2,5-diethynylthiophene, hexenediyne, octatetrayne, butenyne, hexenediyne, and octadienediyne. Some meso-to-β dimers were also made. The dimers are complemented by a set of monomers containing the bridging units as mesosubstituents. The compounds were prepared by a combination of palladium-catalyzed couplings of alkynes with unsaturated halides and oxidative alkyne couplings. The separate effects of the substituents and the presence of the second porphyrin chromophore are delineated by comparisons of the visible absorption spectra for the various monomers and dimers. The dimers fit into three spectral classes: (i) those displaying strongly split Soret bands indicative of inter-porphyrin conjugation (diyne, tetrayne, enediyne, enyne, diethynylthiophene), (ii) those in which this conjugation is interrupted (diethynylbenzenes), and (iii) those with double bonds attached to the meso-carbons, which exhibit broad, low-energy bands, but small splittings of the Soret band. These illustrate some of the promising light-harvesting properties which can be achieved by tailoring the composition of the conjugating bridges linking the units in multi-porphyrin arrays.

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A cobalt porphyrin equipped with two different but geometrically complementary pyridine ligands self-assembles to form an unusually stable complex with approximately 12 porphyrin monomers arranged in a macrocyclic array.

A series of novel indolizine 2-oxoacetamides were designed and synthesized as PDE4 inhibitors. Preliminary SAR of this new class of compounds revealed key structural features required for high potency. Compounds 1ab and 2a are among the most potent inhibitors of PDE4 with low single nM IC 50 . Cellular activity was demonstrated by the inhibition of TNFa production from human PBMC with IC 50 ranging from 14 to 72 nM. Docking analyses suggest the OH group in 1ab enhance the binding via an H-bond interaction with the PDE4 enzyme.

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A series of tetra(hydroxyphenyl)-(2-, 3- and 4-hydroxy; THPP) and tetrakis(dihydroxyphenyl)porphyrins (2,3-, 2,4-, 2,5-, 3,4-, and 3.5-dihydroxy; TDHPP) was synthesized and tested for toxicity in HeLa cells and human melanoma cell lines. Irradiation of drug-treated cells with > 600 nm light greatly increased the toxicity of all drugs except the 2,5- and 3,5-TDHPP. The THPP were more toxic than TDHPP in all cell lines, with or without irradiation; of the dihydroxy derivatives, the 3,4- and 2,4-isomers were the most toxic and the 2,5-isomer was the least toxic. The MM96E melanoma cell line, shown previously to be sensitive to hydrogen peroxide and superoxide ion, was not hypersensitive to killing by any of the above agents. HeLa cells, which lacked glutathione-S-transferase activity, were sensitive to the 4- and 2,3-isomers after irradiation; similar amounts of all drugs were taken up by HeLa cells. The pigmented melanoma cell line MM418, resistant to UV-B and in situ-generated hydrogen peroxide but sensitive to glutathione (GSH) depletion, was found to be resistant to the 2,3-isomer (no irradiation) and sensitive to the 3,4-isomer. The results indicate that (1) phototoxicity in these phenylporphyrins is not mediated by superoxide ions or hydroxyl radicals, (2) toxicity is dependent on the orientation of the hydroxy groups, (3) GSH transferase and possibly GSH itself offer protection from the 4- and 3,4-derivatives, respectively, and (4) the 3,4-derivative and analogues of similar selectivity should be evaluated further for the treatment of primary melanoma.

The conjugated bridge and the attached meso-carbons in the title dimer are almost coplanar; the porphyrin rings are ruffled and distorted in this vicinity, indicating strong interporphyrin interaction via the n-orbitals of the diethynylthiophene unit.

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