The indolin-2-one fused-ring system and the 2,4-dimethylpyrrole unit represent key structural motifs in the anticancer drug sunitinib (Sutent®) and predecessor angiogenesis inhibitors that have undergone anticancer clinical trials (e.g. semaxanib, SU5416). In pursuit of novel anti-angiogenic scaffolds, we were interested in identifying whether the indolin-2-one group in these structures could be modified without losing activity. This paper describes novel condensation chemistry used to prepare a test series of (E)- and (Z)-alkenes related to SU5416 that retain the 2,4-dimethylpyrrole unit while incorporating ring-opened indolin-2-ones. Unique structural characteristics were identified in the compounds, such as intramolecular hydrogen bonds in the (Z)-alkenes, and several examples were shown to possess significant anti-angiogenic activity in a rat aorta in vitro model of angiogenesis. The work demonstrates that the indolin-2-one moiety is not an absolute requirement for angiogenesis inhibition in the sunitinib/SU5416 class.

Knoevenagel condensation has been utilized as an alternative way to synthesize a series of β‐vinyl‐substituted porphyrins and porphyrin dyads with good to excellent yields. The condensation of β‐formyl porphyrins and phenylacetonitriles allows control of the substitution pattern and metal centres in the porphyrin dyads, allowing the use of metallated synthons. While the optical and electronic properties of the resulting porphyrin dyes are perturbed by the presence of the cyano substituent, this does not significantly affect their use. For example, Raman spectroscopy, in agreement with density functional theory (DFT) and time‐dependent DFT (TD‐DFT) calculations, show porphyrin electronic transitions with delocalization of frontier molecular orbital electron density onto the β substituent. A comparison of the photovoltaic performance of a carboxylated cyanostyryl condensation product and the unsubstituted analogue in dye‐sensitized solar cells (DSSCs) was made. Although the devices showed similar efficiency, the device containing the cyano‐substituted dye showed an extended incident photon‐to‐current conversion efficiency (IPCE) due to a slight red‐shift in absorption and an increase in photovoltage as a result of a longer electron lifetime. This minimal change in light‐harvesting performance highlights the potential of this Knoevenagel synthetic methodology for producing light‐harvesting porphyrin dyes.

The emulation of photosynthesis, the efficient and sustainable utilization of solar energy using renewable materials to produce hydrogen and oxygen from water or convert carbon dioxide into a chemical feedstock represents one of the great scientific challenges of the 21st Century. Creating photosynthetic-like processes in devices could not only provide a new generation of economical photovoltaic devices but also lead to sustainable hydrogen production through water splitting as well as fuel and food production through carbon dioxide fixation.  The challenge in building a useful ‘artificial photosynthetic’ assembly is not simply using or mimicking the natural photosynthetic apparatus but utilizing new materials to create and, if possible, improve the structural properties and functionality of the biological system. In 1994, Dutton et al. developed the methodology for the facile production of de novo synthetic protein helices1 (maquettes), structurally simpler analogs of natural redox proteins, which have proved extremely useful for the study of porphyrin behaviour and interactions in proteins (heme, chlorophyll, light-activated zinc porphyrins).2 It has been demonstrated that not only is a maquette-bound porphyrin more efficiently photo-oxidized than the analogous free porphyrin but also that light-induced electron transfer between the porphyrin complex and an added acceptor is faster and higher yielding.3 As the maquettes can be assembled on a variety of surfaces such as gold or titanium dioxide, they provide a unique platform on which to build and study a light harvesting reaction centre reproduction.  Over the last 10 years, we have developed syntheses of single porphyrins and porphyrin arrays and utilized the resulting materials as light harvesters in dye sensitized solar cells bound through carboxyl-based linkers to titanium dioxide.4 However, the introduction of porphyrins into water-soluble maquettes requires the development of amphiphilic porphyrins and porphyrin arrays.  Here we present the syntheses and incorporation of single porphyrin and amphiphilic porphyrin dimers into maquettes and the characterisation of the resulting porphyrin-maquette assemblies.  In order to assess the potential of the porphyrin maquette and as a first step in the development of an artificial photosynthetic reaction centre, we have bound a porphyrin maquette to titanium dioxide and used it as a photoanode in a solar cell; we will discuss the characteristics of this first artificial protein-based photovoltaic device. REFERENCES 1. D. E. Robertson, R. S. Farid, C. C. Moser, J. L. Urbauer, S. E. Mulholland, R. Pidikiti, J. D. Lear, A. J. Wand, W. F. DeGrado, P. L. Dutton, Nature (London, United Kingdom) 1994, 368, 425. 2. B. M. Discher, R. L. Koder, C. C. Moser, P. L. Dutton, Curr. Opin. Chem. Biol. 2003, 7, 741. 3.  M. R. Razeghifard, T. Wydrzynski, Biochemistry 2003, 42, 1024. 4.  A. J. Mozer, M. J. Griffith, G. Tsekouras, P. Wagner, G. G. Wallace, S. Mori, K. Sunahara, M. Miyashita, J. C. Earles, K. C. Gordon, L. Du, R. Katoh, A. Furube, D. L. Officer, J. Am. Chem. Soc. 2009, 131, 15621.