Pyrazinochlorins – at long last

A paper describing the expansion of a pyrrolic building block in meso-tetraphenylporphyrins by a nitrogen atom generating pyrazinoporphyrins was finally published (Eur. J. Org. Chem. 2016, DOI: 10.1002/ejoc.201501436)! The work goes back to 2000, when CB himself still worked in the lab and made the stable nickel complexes, but he was never able to make the much trickier to make but more interesting free base derivatives. This was accomplished by Michelle Head (neé Dean), PhD 20011 (her pyrazinoporphyrin syntheses were done in 2007-2008), and Gloria Zarate, M.S. 2010! Good things sometimes take a long while!

Biliverdin oxidation paper is published

This paper presents the first structural model of the oxidation products of biliverdin. Biliverdin dimethyl ester, extracted from Emu eggshells, was shown to be oxidized by singlet oxygen, and the oxidation products were structurally characterized. While the role of biliverdin as a biological antioxidant is long known (albeit its role is Emu eggshells may simply be as a color to camouflage the eggshell from predators) and its reactivity with singlet oxygen was also shown before, the nature of the reaction products remained hitherto unknown.  Thus, this study helps to understand the molecular mechanism of the antioxidant action of biliverdin.

Dorazio, S.; Halepas, S.; Fleming, K. M.; Zeller, M.; Bruhn, T.; Brückner, C. ‘Singlet Oxygen Addition Products of Biliverdin IXα Dimethyl Ester’ Bioorg. Med. Chem. 2015, 23, 7671–7675 (DOI:10.1016/j.bmc.2015.11.012).

For Sarina’s AudioSlide presentation of the papers, see:

Our NSF Proposal on the Study of Pyrrole-Modified Porphyrins was Renewed!

The main objective of this proposal is the continuation of our program to develop strategies to convert porphyrins into pyrrole-modified porphyrins (PMPs). PMPs are macrocycles derived from porphyrins by formally replacing at least one pyrrolic building block with a different heterocycle. Starting from meso-arylporphyrins or octaethyl­porphyrin, a relatively little explored but most successful and versatile strategy will be pursued: activation of the β‑position of porphyrins, followed by ring cleavage and subsequent ring-fusion. This generates PMPs containing one or two five, six, and seven-membered non-pyrrolic heterocycles. They may also incorporate extended π-systems through β-to-meso-phenyl linkages.

The guiding hypothesis of the work – supported by our earlier work – is that these modifications result in drastically altered electronic properties when compared to their parent porphyrins or chlorins. Particularly with respect to their longest wavelength of absorbance and fluorescence, their hyperchromic and, in some cases, pan­chromic spectra, and in their efficient non-radiative relaxation processes, many PMPs possess remarkable physical properties of potential utility. We will evaluate the (photo)physical and chemical properties of the PMPs. This data will be correlated with their structural parameters such as degree of saturation, bulk of the substituents, degree of non-planarity, and conformational flexibility.


Indachlorins: Chlorin Analogues with Panchromatic Absorption Spectra Between 300 and 900 nm

Indaphyrins, pyrrole-modified porphyrins containing a cleaved pyrrole β,β’-bond and two annulated indanone moieties, possess unusually broadened and redshifted UV/Vis spectra because of their π-expanded chromophores. Its free base has been crystallographically characterized, highlighting its strongly ruffled conformation incorporating a helimeric twist. Free base indaphyrin was shown to be susceptible to regiospecific derivatizations at the opposite side of the ring-cleaved pyrrole (dihydroxylation, followed by functional group transformations of the resulting diol functionality), generating indaphyrin-based chlorin analogues, indachlorins, that incorporate a dihydroxypyrroline, pyrrolindione, oxazolone, or a morpholine moiety. Structural modifications resulted in further broadening and hyper- and bathochromic shifts of the optical spectra, some of which possess a nearly panchromatic absorption between 300 to well above 900 nm. The extents to which these modifications affect their solid-state conformations were analyzed:

Samankumara, L.; Dorazio, S.; Akhigbe, J.; Li, R.; Nimthong-Roldán, A.; Zeller, M.; Brückner, C. ‘Indachlorins: Nonplanar Indanone-Annulated Chlorin Analogues with Panchromatic Absorption Spectra Between 300 and 900 nm’ Chem.–Eur. J. 2015, accepted for publication.

Internal Funding to Investigate Our Photoacoustic Imaging Dyes Provided through the Research Excellence Program

Funding by the Research Excellence Program (REP) of the UConn VP of Research, our group in collaboration with the group of Quing Zhu (UConn, Electrical and Computer Engineering), received seed funding: ‘Near-IR Absorbing and Emitting Porphyrinoids as Fluorescence and Photoacoustic Tissue Imaging Dyes’ (PI C. Brueckner; co-PI Quing Zhu, $50,000, 2015-2016).

Non-invasive high-resolution imaging of tissue has become increasingly important in biomedical diagnosis. Optical methods using near-infrared (NIR) wavelengths are particularly appealing since only NIR light penetrates tissue deeply – the NIR wavelengths between ~700 and 900 nm define the so-called spectroscopic window of tissue. Furthermore, low-energy NIR light is non-damaging to tissue, even under extended illumination, thus enabling longitudinal studies. Two specific emerging biomedical imaging technologies utilizing NIR-absorbing dyes are photoacoustic imaging (PAI) and fluorescence diffuse optical tomography (FDOT):

In PAI, the absorption of a light pulse by some dyes causes a photoacoustic effect. In essence, the absorption of light can be heard (in the ultrasonic regime). As a pulsed NIR beam is scanned through the tissue, the emitted ultrasonic wave profile is acquired and the data are used to construct 2D or 3D optical absorption maps. PAI combines the advantages of high optical contrast and ultrasound (sub-mm) spatial resolution.

FDOT provides depth-resolved spatial distributions of fluorescence in tissues with very high sensitivity. The fluorescence is captured by a detector array and used to construct 2D optical fluorescence maps.

The biggest challenge for clinical applications of both techniques for the imaging of deeply-seated tumors (or other lesions or organs) with high sensitivity is the development of contrast agents/tracers that absorb NIR light and that exhibit a photoacoustic effect or emit in the NIR. In general, few dyes absorb in the NIR regime, and even fewer are have strong photoacoustic or fluorescence responses.

We propose to:

  • Screen a wider range of near-IR-absorbing dyes (commercial dyes as well as dyes prepared in our labs) under the highly controlled conditions of the tissue phantom experiment to begin to map structure-photophysical properties-PAI function relationships, something we are not aware of has been accomplished for any class of PAI dyes, but that is very important for the directed development of optimized PAI contrast agents.
  • The dyes prepared to date are only soluble in organic solvents and are thus unsuitable for use in ex vivo tissue samples or mice. Hence, water-soluble derivatives of the known chromophores will be prepared.

Depending on the photophysical characteristics of the dyes, the water-soluble dyes will be used in in vivo PAI or FDOT imaging experiments using mouse models.

The Introduction of Carboxyl Groups to Pentaflurophenyl-Substituted Porphyrins is Facile

A first collaborative paper with the Agrios Group, UConn Department of Civil and Environmental Engineering and Center for Clean Energy Engineering (C2E2) was published: Hewage, N.; Bowen; Agrios, A. G.; Brückner, C. ‘Introduction of Carboxylic Ester and Acid Functionalities to meso‑Tetrakis(pentafluorophenyl)porphyrin and their Limited Electronic Effects on the Chromophore’ Dyes Pigm. 2015, 121, 159–169.

Alkyl- or aryl-carboxylic acid-functionalized porphyrinic dyes are sought after because of their propensity to adhere strongly to many metal oxide surfaces as required for their application as, for instance, sensitizers in dye-sensitized solar cells (DSSCs), in air purification, or chemosensing systems. The SNAr reaction of the pentafluorophenyl group is a versatile method to introduce functionality into mesopentafluorophenyl- substituted porphyrins. The conditions to introduce one through four alkyl- or aryl-carboxyl functionalities using mercaptopropionate or 3,4-dihydroxybenzoate esters, respectively, are explored, and the regioisomeric products are spectroscopically characterized. Their saponification to the corresponding carboxylic acids was studied. By experimental determination of their optical properties (absorption and emission spectroscopy) and their frontier orbital positions by cyclic voltammetry, we demonstrate the minimal electronic influence this derivatization method has on the chromophore.

See also the Audioslide presentation of article.

Indaphyrins and Indachlorins: Optical and Chiroptical Properties of a Family of Helimeric Porphyrinoids

Another paper resulting from the collaboration with the Bringmann Group at the University of Würzburg was published! Indaphyrins and indachlorins possess large chiral porphyrinoid π-systems with particularly long-wavelength absorption properties. All indaphyrin derivatives, including the indaphyrin M(II) complexes (M = Ni(II), Cu(II), Zn(II), and Pt(II)), adopt strongly ruffled and metal-dependent conformations incorporating a helimeric twist, thus forming two stereochemically stable helimeric enantiomers. Resolution of the racemic mixtures of the helimers of all derivatives Introduction was achieved by HPLC on a chiral phase and their absolute stereostructures were assigned. The much altered UV/Vis spectra of the indaphyrin derivatives, when compared to those of porphyrins, were rationalized using excited state calculations. The report forms the basis for future applications that exploit the chiral properties of the chromophores: Götz, D. C. G.; Gehrold, A.; Dorazio, S.; Samankumara, L.; Daddario, P.; Bringmann, G.; Brückner, C.; Bruhn, T. Eur. J. Org. Chem. 2015, 3913–3922.

Why is there Cyanide in my Table Salt?

Yellow Prussiate of Soda (YPS, Na4[Fe(CN)6]·10H2O) is an approved anticaking agent in table salt. Given that it is a cyanide salt, its use as a food additive is surprising. In a recently accepted manuscript (Dorazio, S. J.; Brückner, C. J. Chem. Educ. 2015, accepted for publication) we highlight recent reports by Bode et al. (Cryst. Growth Des. 2012, 12, 1919. and  ibid. 5889.) on the mode of action of sub-monoatomic layers of YPS on NaCl crystals to act as an anticaking agent through nucleation inhibition . The molecular-level explanation reinforces the notion of how structure and charge affect the properties of matter. In addition, we report a simple naked eye analytical method of detecting YPS on store-bought table salt in the form of the pigment Prussian Blue (Fe4[Fe(CN)6]3·xH2O).