Synthesis and photodynamic properties of conjugated acyclic and cyclic pyrrole-containing compounds
50000403v1838
Promoter: Wim Dehaen
details
Description: Corroles, contracted porphyrin analogues lacking one meso-carbon atom, have been rather rare macrocyclic compounds for a long time due to their challenging synthesis. Novel one-step synthetic methods towards (more stable) meso-triarylcorroles and the discovery that corroles can stabilize unusually high metal oxidation states have, however, given a new impulse to corrole chemistry.
Within our group, a lot of research was carried out recently on the synthesis of acyclic and cyclic oligopyrroles, including dipyrromethenes, porphyrins, corroles, hexaphyrins, and calixphyrins. We have recently developed an efficient synthetic route towards meso-pyrimidinyl substituted A2B-corroles, which uses a [2+1]-condensation of aryldipyrromethanes and 4,6-dichloropyrimidine-5-carbaldehydes. Besides the high yields for the corrole synthesis, the main advantage of the presented meso-pyrimidinylcorroles is the high reactivity of the chlorine groups towards functionalization. Different substitution reactions, e.g., nucleophilic aromatic substitution (SNAr) and metal-catalyzed cross-coupling reactions (Suzuki, Stille, Liebeskind), have successfully been explored at the corrole stage. Using these reactions, it is possible to construct sophisticated functional corroles and multichromophoric systems, suitable for a variety of corrole applications, e.g., (asymmetric) catalysis, molecular electronics, and photodynamic therapy (PDT).
Corroles are chromophores (usually purple colored) with distinct absorption bands in the visible region and an intense (orange-red) fluorescence. Due to their high affinity for tumors, they are particularly attractive as active components for fluorescence diagnosis (photodetection) and treatment (PDT) of various cancer types. PDT is a modern medical treatment that uses a drug, called a photosensitizer, and a particular type of light. When photosensitizers are exposed to a specific wavelength of light, they produce highly reactive singlet oxygen (1O2) that kills nearby (tumor) cells. In order to be able to apply a photosensitizer in vivo, it should be sufficiently soluble in living tissue and body fluids.
In this project we will focus on the synthesis of amphiphilic corroles as potential photosensitizers. Using SNAr and Pd-catalyzed cross-coupling reactions as done before for related pyrimidine-containing systems, diverse polar functional groups will be introduced on the chloro substituted pyrimidinylcorroles that were prepared earlier. The amount of pyrimidinyl groups may vary from 1 to 3 in this case. We will also prepare and functionalize the corresponding porphyrins and BODIPYs (boron-chelated dipyrromethenes) and compare their properties with the functionalized corroles. All compounds prepared will be fully characterized by NMR, UV and fluorescence, FTIR, and MS spectroscopies.
A selection of recent, earlier related work in the laboratory of organic synthesis in Leuven
S. A. Chavan, W. Maes, L. E. M. Gevers, J. Wahlen, I. F. J. Vankelecom, P. A. Jacobs, W. Dehaen, D. E. Devos, “Porphyrin-functionalized dendrimers : synthesis and application as recycable photocatalysts in a nanofiltration membrane reactor”, Chem. Eur. J. 2005, 6754-6762.
T. Rohand, M. Baruah, W Qin, N. Boens, W. Dehaen, “Functionalisation of fluorescent BODIPY dyes by nucleophilic substitution”, Chem. Commun. 2006, 266-268.
W. Maes, T. N. Ngo, J. Vanderhaeghen, W. Dehaen, “Meso-pyrimidinyl- substituted A2B-corroles”, Org. Lett. 2007, 9, 3165-3168.
W. Qin, T. Rohand, W. Dehaen, J. N. Clifford, K. Driesen, D. Beljonne, B. Van Averbeke, M. Van der Auweraer, N. Boens, “Borondipyrromethene analogs with phenyl, styryl, and ethynylphenyl substituents: synthesis, photophysics, electro-chemistry, and quantum-chemical calculations”, J. Phys. Chem(A)., 2007, 111, 8588-8597.
T. Rohand, J. Lycoops, S. Smout, E. Braeken, M. Sliwa, M. Van der Auweraer, W. Dehaen, W. M. De Borggraeve, N. Boens, “Photophysics of 3,5-diphenoxy substituted BODIPY dyes in solution”, Photochem. Photobiol. Sci. 2007, 6, 1061-1066
I. Szymanska, C. Orlewska, D. Janssen, W. Dehaen, H. Radecka, “Dipyrromethene-dodecanethiol self assembled monolayers deposited on gold electrodes”, Electrochim. Acta, 2008, 53, 7932-7940.
B. Saraswathyamma, M. Pajak, J. Radecki, W. Maes, W. Dehaen, G. Kumar, H. Radecka, „PVC supported liquid membrane and carbon paste potentiometric sensors incorporating Mn (III) porphyrin for direct determination of undissociated paracetamol”, Electroanalysis, 2008, 20, 2009-2015.
I. Szymanska, M. Stobiecka, C. Orlewska, T. Rohand, D. Janssen, W. Dehaen, H. Radecka, „Electroactive dipyrromethene-Cu(II) self assembled monolayers-complexation reaction on the surface of gold electrodes”, Langmuir, 2008, 24, 11239-11245.
B. Saraswathyamma, I. Grzybowska, C. Orlewska, J. Radecki, W. Dehaen, K. G. Kumar, H. Radecka, „Electroactive dipyrromethene-Cu(II) monolayers deposited onto gold electrodes for voltammetric determination of paracetamol”, Electroanalysis, 2008, 20, 2317-2323.
W. Qin, V. Leen, T. Rohand, W. Dehaen, P. Dedecker, M. Van der Auweraer, K. Robeyns, L. Van Meervelt, D. Beljonne, B. Van Averbeke, J. N. Clifford, K. Driesen, K. Binnemans, N. Boens, „Synthesis, spectroscopy, crystal structure, electrochemistry, and quantum chemical and molecular dynamics calculations of a 3-anilino difluoroboron dipyrromethene dye” J. Phys. Chem., 2009, 113, 439-447.
T. H. Ngo, W. Van Rossom, W. Dehaen en W. Maes, „Reductive demetallation of Cu-corroles- a new protective strategy towards functional free-base corroles”, Org. Biomol. Chem. 2009, 439-443.
V. Leen, E. Braeken, K. Luckermans, C. Jackers, M. Van der Auweraer, N. Boens, W. Dehaen, “A versatile, modular synthesis of monofunctionalized BODIPY dyes”, Chem. Commun. 2009, 4515-4517.
W. Qin, V. Leen, W. Dehaen, J. Cui, C. Xu, X.Tang, W. Liu, T. Rohand, D. Beljonne, B. Van Averbeke, J. N. Clifford, K. Driesen, K. Binnemans, M. Van der Auweraer, N. Boens, “3,5-Dianilino Substituted Difluoroboron Dipyrromethene: Synthesis, Spectroscopy, Photophysics, Crystal Structure, Electrochemistry, and Quantum-Chemical Calculations”., J. Phys. Chem. C 2009, 113, 11731-11740.
E. Fron, E. Coutino-Gonzalez, L. Pandey, M. Sliwa, M. Van der Auweraer, F. C. De Schryver, J. Thomas, Z. Dong, V. Leen, M. Smet, W. Dehaen, T. Vosch, “Synthesis and photophysical characterisation of chalcogen substituted BODIPY dyes”, New J. Chem. 2009, 33, 1490-1496.
K. Kurzatkowska, E. Dolusic, W. Dehaen, K. Sieron-Stoltny, A. Sieron, H. Radecka, “Gold Electrode Incorporating Corrole as an on-channel mimetic for determination of Dopamine” Anal. Chem. 2009, 81,7397-7405.
I. Szymanska, E. Dolusic, W. Dehaen, W. Maes, T. Ito and H. Radecka, Determination of interaction strength between corrole and phenol derivatives in aqueous media using atomic force microscopy”, Supramol. Chem. 2009, 21, 555-563.
W. Maes, W. Dehaen “Synthetic aspects of porphyrin dendrimers”, Eur. J. Org. Chem., 2009, 4719-4752.
V. Leen, F. Schevenels, J. Cui, C. Xu, W. Yang, X. Tang, W. Liu, W. Qin, W. M. De Borggraeve, N. Boens, W. Dehaen, “Synthesis and substitution of 8-(4,6-dichloropyrimidin-5-yl)BODIPY” Eur. J. Org. Chem., 2009, 5920-5926.
T. H. Ngo, F. Nastasi, F. Puntoriero, S. Campagna, W. Dehaen, W. Maes, "Meso-pyrimidinyl-Substituted A2B- and A3-Corroles", J. Org. Chem., accepted
Key words: Corroles, oligopyrroles, ligands, photodynamic therapy
Latest application date: 2010-05-17
Financing: Erasmus Mundus External Cooperation Window
Type of Position: scholarship
Source of Funding: EMECW
Duration of the Project : 3-4 years
Research group: Department of Chemistry
Remarks: Take deadlines of EMECW funding system into account
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