Diketopyrrolopyrrole Derivatives as Photosensitizing Agents against Staphylococcus aureus.

Diketopyrrolopyrrole (DPP) derivatives containing sulfonamide (Sulfonamide-DPP), pyridyl (Dipyridyl-DPP) and N-methylpyridyl (MePyridyl-DPP) substituents were assessed as antibacterial photosensitizers. Non-charged DPPs showed an intense absorption band centered at about 480 nm and green fluorescence emission (ΦF ~ 0.7) in acetonitrile. The absorption of MePyridyl-DPP was bathochromically shifted at 510 nm, with decreased fluorescence emission. Sulfonamide-DPP and Dipyridyl-DPP photosensitized the formation of O2 (1 Δg ) (ΦΔ ~ 0.15-0.17), while the production induced by MePyridyl-DPP was at least 10 times lower. Furthermore, these DPPs produced a photoreduction of NBT similar to that of the control. Photodynamic inactivation induced by DPPs was first investigated at the single-bacterium level of Staphylococcus aureus attached to a surface. After 30 min irradiation, MePyridyl-DPP produced a complete eradication of the bacteria. In bacterial cell suspensions, dicationic DPP induced more than 7 log10 decrease in S. aureus cell survival after 30 min irradiation. Potentiation with iodide anions allowed a complete elimination of bacteria after 15 min therapy. This compound was also effective to eliminate S. aureus cells on biofilms. The results show that MePyridyl-DPP bearing two positive groups provides an amphiphilic character to the structure that improves the interaction with the cell envelop. This effect enhances the photocytotoxic activity of MePyridyl-DPP against bacteria.

Synthesis of Novel Diketopyrrolopyrrole-Rhodamine Conjugates and Their Ability for Sensing Cu2+ and Li.

The search for accurate and sensitive methods to detect chemical substances, namely cations and anions, is urgent and widely sought due to the enormous impact that some of these chemical species have on human health and on the environment. Here, we present a new platform for the efficient sensing of Cu2+ and Li+ cations. For this purpose, two novel photoactive diketopyrrolopyrrole-rhodamine conjugates were synthesized through the condensation of a diketopyrrolopyrrole dicarbaldehyde with rhodamine B hydrazide. The resulting chemosensors 1 and 2, bearing one or two rhodamine hydrazide moieties, respectively, were characterized by 1H and 13C NMR and high-resolution mass spectrometry, and their photophysical and ion-responsive behaviours were investigated via absorption and fluorescence measurements. Chemosensors 1 and 2 displayed a rapid colorimetric response upon the addition of Cu2+, with a remarkable increase in the absorbance and fluorescence intensities. The addition of other metal ions caused no significant effects. Moreover, the resulting chemosensor-Cu2+ complexes revealed to be good probes for the sensing of Li+ with reversibility and low detection limits. The recognition ability of the new chemosensors was investigated by absorption and fluorescence titrations and competitive studies.

Diketopyrrolo[3,4-c]pyrrole derivative as a promising ligand for the stabilization of G-quadruplex DNA structures.

Telomerase, oncogenes and tumor suppressors are closely associated with tumour occurrence, therefore these structures are being recognized as targets for the development of new anticancer drugs. The efficacy of several molecules in telomerase inhibition and regulation of genes expression, by adduct formation with G-quadruplexes (G4), has been studied by biophysical and biochemical methods with promising results. We report here the synthesis and structural characterization of a small positively charged diketopyrrolo[3,4-c]pyrrole derivative, identified as DPP(PyMe)2, that showed very promising results as G4 stabilizing ligand. The data obtained from UV-Vis and fluorescence experiments suggest that DPP(PyMe)2 presents high affinity to G4 structures. Docking studies and molecular dynamics simulations unraveled the binding modes of the ligand with four G4 structures. The obtained results also allowed us to conclude that the DPP(PyMe)2 ligand binds into the top G-tetrad or in a mixed binding mode depending on the GQ structure. A remarkable selectivity of DPP(PyMe)2 for c-MYC and KRAS 32R in the presence of ds26 was observed by circular dichroism (CD) and fluorescence resonance energy transfer (FRET) melting experiments. CD titrations revealed a stabilization higher than 30 °C in the case of c-MYC G4 structure and, for the same sequence, DPP(PyMe)2 showed the ability to block the activity of Taq polymerase in a dose-dependent manner. The subcellular localization obtained with confocal microscopy corroborates the results obtained by the other techniques and the obtained data suggest that DPP(PyMe)2 is an attractive ligand for the development of G4 labelling probes.

A Convenient Synthesis of Diketopyrrolopyrrole Dyes.

Diketopyrrolo[3,4-c]pyrroles (DPP) are high-performance organic optoelectronic materials. They have applications in solar cells, fluorescent probes, bioimaging, photodynamic/photothermal therapy, and in many other areas. This article reports a convenient two-step synthesis of various DPP dyes from Pigment Red 254, an inexpensive commercial pigment. The synthesis includes a Suzuki-Miyaura cross-coupling reaction of a bis(4-chlorophenyl)DPP derivative with aryl and hetaryl boronic acids under mild reaction conditions. The new dyes show large Stokes shifts and high fluorescence quantum yields, important features for their potential use in technical and biological applications.

Diketopyrrolopyrrole-fullerene C60 architectures as highly efficient heavy atom-free photosensitizers: synthesis, photophysical properties and photodynamic activity.

Chromophore-fullerene C60 hybrids possess interesting properties that enable them to act as heavy atom-free photosensitizers and reactive oxygen species (ROS) producers. Here, two new diketopyrrolopyrrole-C60 conjugates were efficiently synthesized and characterized. The conjugates show broadband absorption in the visible spectral region, in which diketopyrrolopyrrole dyes act as light-harvesting antenna with very high capacity to populate excited triplet states. Furthermore, the ability of diketopyrrolopyrrole-C60 systems to generate singlet molecular oxygen was explored for the first time in solvents of different polarities. The experimental results show that these architectures exhibit very high production rates of this ROS. In addition, a preliminary study on Staphylococcus aureus cell suspensions indicates that both conjugates exhibit phototoxicity after irradiation with green LED light. Thus, the data obtained provide evidence that these diketopyrrolopyrrole-C60 architectures act as potential heavy atom-free photosensitizers in photodynamic inactivation of microorganisms and other singlet oxygen-mediated applications.

Coumarin-Tetrapyrrolic Macrocycle Conjugates: Synthesis and Applications.

This review covers the synthesis of coumarin-porphyrin, coumarin-phthalocyanine and coumarin-corrole conjugates and their potential applications. While coumarin-phthalocyanine conjugates were obtained almost exclusively by tetramerization of coumarin-functionalized phthalonitriles, coumarin-porphyrin and coumarin-corrole conjugates were prepared by complementary approaches: (a) direct synthesis of the tetrapyrrolic macrocycle using formylcoumarins and pyrrole or (b) by functionalization of the tetrapyrrolic macrocycle. In the last approach a range of reaction types were used, namely 1,3-dipolar cycloadditions, hetero-Diels-Alder, Sonogashira, alkylation or acylation reactions. This is clearly a more versatile approach, leading to a larger diversity of conjugates and allowing the access to conjugates bearing one to up to 16 coumarin units.