Sara M.A. Pinto

Synthesis of New Metalloporphyrin Triads: Efficient and Versatile Tripod Optical Sensor for the Detection of Amines

Zinc and manganese complexes of porphyrin triads have been synthesized and are shown to be efficient as highly sensitive and selective tripod optical sensors for amines at the picomolar level.

Ecofriendly Porphyrin Synthesis by using Water under Microwave Irradiation

Water, under microwave irradiation and at a temperature of 473 K, reaches pressures above 16 bar, being capable to act as catalyst, without the use of organic solvents and oxidants, for meso-substituted porphyrin synthesis. Sustainability of the reaction is proved by E Factor=35 and EcoScale value of 50.5, the highest so far obtained for porphyrin synthesis. Methodologys wide versatility is clearly demonstrated by the good yields obtained for both aryl and alkyl substituted porphyrins. These reaction conditions represent a huge development, not only by using very high concentrations, minimizing organic solvent usage, but also by eradicating toxic expensive solvents and oxidants.

Singlet-singlet energy transfer in self-assembled systems of the cationic poly{9,9-bis[6-N,N,N-trimethylammonium)hexyl]fluorene-co-1,4-phenylene} with oppositely charged porphyrins.

Electronic energy transfer has been studied between the cationic conjugated polyelectrolyte, poly{9,9-bis[6-N,N,N-trimethylammonium)hexyl]fluorene-co-1,4-phenylene} dibromide (HTMA-PFP), and three, oppositely charged meso-tetrakis-phenylporphyrinsulfonates in buffered (pH = 9.2), 4% (v/v) dimethyl sulfoxide-water (DMSO-water) solutions using steady-state and time-resolved fluorescence. Energy transfer was indicated by the decrease in intensity of the fluorescence band of the HTMA-PFP donor, by a corresponding increase in fluorescence of the porphyrin acceptors, by a band in the excitation spectrum of the porphyrin corresponding to the polymer absorption, and by the fact that the decay of the polymer emission observed at 423 nm was accompanied by the grow-in of porphyrin emission at 650 nm in time-resolved measurements. It is suggested that the energy transfer may involve upper excited states of the acceptor. The Förster equation and the experimental spectral overlap between donor fluorescence and acceptor absorption were used to calculate Förster radii for the three systems. Both steady-state and dynamic Stern-Volmer plots were nonlinear at high acceptor concentrations, and quenching rate constants calculated from the slopes of the initial linear region and the HTMA-PFP fluorescence lifetime were orders of magnitude greater than expected for a diffusion-controlled process, strongly supporting the idea that energy transfer occurs in self-assembled species formed by association (through ion pairing) of the polymer and porphyrins. There are indications that these aggregates involve more than one polymer chain. Picosecond time-resolved measurements on the HTMA-PFP fluorescence decay showed a short-lived component, attributed to the energy-transfer step, and two longer lived decays, which may be associated with exciton migration along the chain and the fluorescence decay of the polymer backbone, respectively. From considerations of the probable distance between donor and acceptor it is suggested that the Forster mechanism, assuming point dipoles, is inadequate for this system and that more detailed calculations, considering the actual sizes of the donor and acceptor, are necessary.

Phthalocyanine Labels for Near-Infrared Fluorescence Imaging of Solid Tumors

Diamagnetic metal complexes of phthalocyanines with n-butoxyl groups in all the α-benzo positions of the macrocycle skeleton, MPc(OBu)8, have strong near-infrared absorptions and intense fluorescences that are Stokes shifted by more than 15 nm. Interestingly, the silicon complex 6 is also remarkably photostable and nontoxic. The use of 6 in the fluorescence imaging of BALB/c mice bearing a 4T1-luc2 tumor in the mammary fat pad unambiguously revealed the presence of the tumor when it was only 1 mm in diameter and was not visible with the naked eye. Compound 6 has an intrinsic ability to accumulate in the tumor, adequate spectroscopic properties, and excellent stability to function as a NIR fluorescent label in the early detection of tumors.

Solventless metallation of low melting porphyrins synthesized by the water/microwave method

Herein, we unveil a new ecofriendly methodology for the synthesis of low melting point meso-substituted metalloporphyrins. The water/microwave (MW) synthetic method was used to prepare low melting point unsymmetrical meso-aryl substituted porphyrins and meso-alkyl substituted porphyrins, which uses water under MW irradiation, acting as the solvent/acid catalyst/oxidant in sub-critical conditions. A straightforward conceptual method for the preparation of their metal complexes in very high yields, in the absence of either solvent or base was followed. Thermomicroscopy studies were carried out to assess the metallation reaction, showing that the process is a typical solventless reaction. Calculation of sustainability classifications such as E factors and EcoScale values (as low as 283 and as high as 82 respectively, for the metallation procedure) and very favorable EHS classification establishes this methodology as one presenting the best sustainability classification on porphyrin synthesis.

Synthesis of a new 18F labeled porphyrin for potential application in positron emission tomography. In vivo imaging and cellular uptake

Herein we report, for the first time, the development, labeling optimization and preliminary biodistribution studies of an [18F] radiolabeled meso-tetraphenylporphyrin. After synthesis and characterization of the “cold” fluorinated porphyrin, the conditions have been transferred to an automated radiochemistry module and the desired 5-(2-[18F]fluoroethoxyphenyl)-10,15,20-triphenylporphyrin was prepared in a radiochemical purity >95%. Moreover, data regarding the uptake into human bladder tumor cells and the radiotracer biodistribution after C57BL/6 mice injection are also presented. The maximum cellular uptake was reached at 45 min and was of 2.5%.

The quest for biocompatible phthalocyanines for molecular imaging: Photophysics, relaxometry and cytotoxicity studies

Water soluble phthalocyanines bearing either four PEG500 or four choline substituents in the macrocyclic structure, as well as their Zn(II) and Mn(III) complexes were synthesized. The metal-free and Zn(II) complexes present relatively high fluorescence quantum yields (up to 0.30), while the Mn(III) complexes show no fluorescence as a consequence of rapid non-radiative deactivation of the Mn(III) phthalocyanine excited states through low-lying metal based or charge-transfer states. The effect of DMSO on the aggregation of the phthalocyanines was studied. It was not possible to obtain the Mn(II) complexes by reduction of the corresponding Mn(III) complexes due to the presence of electron donating substituents at the periphery of the phthalocyanines. The (1)H NMRD plots of the PEG500 and choline substituted Mn(III)-phthalocyanine complexes are typical of self-aggregated Mn(III) systems with r1 relaxivities of 4.0 and 5.7mM(-1)s(-1) at 20MHz and 25°C. The Mn(III)-phthalocyanine-PEG4 complex shows no significant cytotoxicity to HeLa cell cultures after 2h of incubation up to 2mM concentration. After 24h of cell exposure to the compound, significant toxicity was observed for all the concentrations tested with IC50 of 1.105mM.

A Cost-Efficient Method for Unsymmetrical Meso-Aryl Porphyrin Synthesis Using NaY Zeolite as an Inorganic Acid Catalyst

Herein we report the synthesis of unsymmetrical meso-aryl substituted porphyrins, using NaY zeolite as an inorganic acid catalyst. A comparative study between this method and the several synthetic strategies available in the literature was carried out. Our method presented a better, more cost-efficient rationale and displayed a significantly lower environmental impact. Furthermore, it was possible to verify the scalability of the process as well as the reutilization of the inorganic catalyst NaY (up to 6 times) without significant yield decrease. In addition, this method was applied to the synthesis of several other unsymmetrical porphyrins, from a low melting point porphyrin to mono-carboxylated halogenated unsymmetrical porphyrins, in yields higher than those found in the literature. Additionally, for the first time, two acetamide functionalized halogenated porphyrins were prepared in high yields. This methodology opens the way to the preparation of high yielding functionalized porphyrins, which can be easily immobilized for a variety of applications, either in catalysis or in biomedicine.

Synthesis of meso-substituted porphyrins using sustainable chemical processes

The easy access and low price of pyrrole and aldehydes, conjugated with the simplicity in preparing meso-substituted porphyrins, makes this type of porphyrins very attractive for a broad range of applications. However, there is an increasing demand for the development of new synthetic processes involving more sustainable chemical principles substituting, whenever possible, dangerous organic solvents by alternative solvents, chromatographic purifications by precipitations and energy-intensive procedures by alternative energy sources such as microwaves and ultrasounds. In this review we will address some recent strategies to synthesize meso-substituted porphyrins using alternative energy sources, reaction media and catalysts, namely microwave irradiation, water as solvent, or solid microporous acid catalysts.

Synthesis of low melting point porphyrins: A quest for new materials

Preparation of porphyrins which do not aggregate, possessing low melting points is an endearing challenge for several applications in materials science. In this contribution a viewpoint regarding the synthesis of low melting point porphyrins, is presented. Herein we review the synthesis of symmetrical and unsymmetrical substituted porphyrins that hold the possibility to be used in several materials science applications and present new results on the spectroscopic and thermal characterization of some low melting point meso-tetrasubstituted porphyrins.