Nicolas Desbois

Slow and Fast Singlet Energy Transfers in BODIPY-gallium(III)corrole Dyads Linked by Flexible Chains

Red (no styryl), green (monostyryl), and blue (distyryl) BODIPY-gallium(III) (BODIPY = boron-dipyrromethene) corrole dyads have been prepared in high yields using click chemistry, and their photophysical properties are reported. An original and efficient control of the direction of the singlet energy transfers is reported, going either from BODIPY to the gallium-corrole units or from gallium-corroles to BODIPY, depending upon the nature of the substitution on BODIPY. In one case (green), both directions are possible. The mechanism for the energy transfers is interpreted by means of through-space Förster resonance energy transfer (FRET).

Evaluation of new iodinated acridine derivatives for targeted radionuclide therapy of melanoma using 125I, an Auger electron emitter

SummaryThe increasing incidence of melanoma and the lack of effective therapy on the disseminated form have led to an urgent need for new specific therapies. Several iodobenzamides or analogs are known to possess specific affinity for melanoma tissue. New heteroaromatic derivatives have been designed with a cytotoxic moiety and termed DNA intercalating agents. These compounds could be applied in targeted radionuclide therapy using 125I, which emits Auger electrons and gives high-energy, localized irradiation. Two iodinated acridine derivatives have been reported to present an in vivo kinetic profile conducive to application in targeted radionuclide therapy. The aim of the present study was to perform a preclinical evaluation of these compounds. The DNA intercalating property was confirmed for both compounds. After radiolabeling with 125I, the two compounds induced in vitro a significant radiotoxicity to B16F0 melanoma cells. Nevertheless, the acridine compound appeared more radiotoxic than the acridone compound. While cellular uptake was similar for both compounds, SIMS analysis and in vitro protocol showed a stronger affinity for melanin with acridone derivative, which was able to induce a predominant scavenging process in the melanosome and restrict access to the nucleus. In conclusion, the acridine derivative with a higher nuclear localization appeared a better candidate for application in targeted radionuclide therapy using 125I.

Porphyrin-based design of bioinspired multitarget quadruplex ligands.

Secondary nucleic acid structures, such as DNA and RNA quadruplexes, are potential targets for cancer therapies. Ligands that interact with these targets could thus find application as anticancer agents. Synthetic G‐quartets have recently found numerous applications, including use as bioinspired G‐quadruplex ligands. Herein, the design, synthesis and preliminary biophysical evaluation of a new prototype multitarget G‐quadruplex ligand, PNAPorphySQ, are reported, where peptidic nucleic acid guanine (PNAG) was incorporated in the porphyrin‐templated synthetic G‐quartet (PorphySQ). Using fluorescence resonance energy transfer (FRET)‐melting experiments, PorphySQ was shown to possess enhanced quadruplex‐interacting properties thanks to the presence of four positively charged PNAG residues that improve its electrostatic interactions with the binding site of both DNA and RNA quadruplexes (i.e., their negatively charged and accessible G‐quartets), thereby making PNAPorphySQ an interesting prototype of a multitarget ligand. Both the chemical stability and water solubility of PNAPorphySQ are improved over the non‐PNA derivative (PorphySQ), which are desirable properties for drug development, and while improvements remain to be made, this ligand is a promising lead for the further development of multitarget G‐quadruplex ligands.

Synthesis, Electrochemistry, and Photophysics of Aza-BODIPY Porphyrin Dyes.

The synthesis of dyad and triad aza-BODIPY-porphyrin systems in two steps starting from an aryl-substituted aza-BODIPY chromophore is described. The properties of the resulting aza-BODIPY-porphyrin conjugates have been extensively investigated by means of electrochemistry, spectroelectrochemistry, and absorption/emission spectroscopy. Fluorescence measurements have revealed a dramatic loss of luminescence intensity, mainly due to competitive energy transfer and photoinduced electron transfer involving charge separation followed by recombination.

cis-Dichloroplatinum(II) complexes tethered to dibenzo[c,h][1,6]naphthyridin-6-ones: Synthesis and cytotoxicity in human cancer cell lines in vitro

A novel family of cisplatin-type complexes tethered to dibenzo[c,h][1,6]naphthyridin-6-one topoisomerase inhibitor via a polymethylene chain and their nonplatinated counterparts were prepared. Their potential cytotoxicity was assessed in three human colorectal cancer cell lines HCT 116, SW480 and HT-29 and compared to the reference molecules cisplatin and oxaliplatin. Platinated compounds were poorly active whilst nonplatinated dibenzo[c,h][1,6]naphthyridin-6-one moieties exhibited higher cytotoxic properties than cisplatin and oxaliplatin whatever the length of the polymethylene chain; molecules containing the tri- and hexamethylene chain length were the most cytotoxic.

Easy access to heterobimetallic complexes for medical imaging applications via microwave-enhanced cycloaddition

Summary The Cu(I)-catalysed Huisgen cycloaddition, known as “click” reaction, has been applied to the synthesis of a range of triazole-linked porphyrin/corrole to DOTA/NOTA derivatives. Microwave irradiation significantly accelerates the reaction. The synthesis of heterobimetallic complexes was easily achieved in up to 60% isolated yield. Heterobimetallic complexes were easily prepared as potential MRI/PET (SPECT) bimodal contrast agents incorporating one metal (Mn, Gd) for the enhancement of contrast for MRI applications and one “cold” metal (Cu, Ga, In) for future radionuclear imaging applications. Preliminary relaxivity measurements showed that the reported complexes are promising contrast agents (CA) in MRI.

Evaluation of two 125I-radiolabeled acridine derivatives for Auger-electron radionuclide therapy of melanoma

SummaryWe previously selected two melanin-targeting radioligands [125I]ICF01035 and [125I]ICF01040 for melanoma-targeted 125I radionuclide therapy according to their pharmacological profile in mice bearing B16F0 tumors. Here we demonstrate in vitro that these compounds present different radiotoxicities in relation to melanin and acidic vesicle contents in B16F0, B16F0 PTU and A375 cell lines. ICF01035 is effectively observed in nuclei of achromic (A375) melanoma or in melanosomes of melanized melanoma (B16F0), while ICF01040 stays in cytoplasmic vesicles in both cells. [125I]ICF01035 induced a similar survival fraction (A50) in all cell lines and led to a significant decrease in S-phase cells in amelanotic cell lines. [125I]ICF01040 induced a higher A50 in B16 cell lines compared to [125I]ICF01035 ones. [125I]ICF01040 induced a G2/M blockade in both A375 and B16F0 PTU, associated with its presence in cytoplasmic acidic vesicles. These results suggest that the radiotoxicity of [125I]ICF01035 and [125I]ICF01040 are not exclusively reliant on DNA alterations compatible with γ rays but likely result from local dose deposition (Auger electrons) leading to toxic compound leaks from acidic vesicles. In vivo, [125I]ICF01035 significantly reduced the number of B16F0 lung colonies, enabling a significant increase in survival of the treated mice. Targeting melanosomes or acidic vesicles is thus an option for future melanoma therapy.

BODIPY–diketopyrrolopyrrole–porphyrin conjugate small molecules for use in bulk heterojunction solar cells

Two small molecules denoted as BD-pPor and BD-tPor composed of a central BODIPY core surrounded with two DPP and two porphyrin units have been designed and synthesized. In BD-pPor and BD-tPor, porphyrins are linked to the central BODIPY by phenyl and thiophene bridges, respectively. The optical and electrochemical properties were systematically investigated in order to employ them as donors along with PC71BM as an acceptor for solution processed bulk heterojunction organic solar cells. After the optimization of the active layer, the organic solar cells based on BD-pPor and BD-tPor exhibit overall power conversion efficiencies of 6.67% and 8.98% with an energy loss of 0.63 eV and 0.50 eV. The low value of energy loss for BD-tPor may be related to the low LUMO offset between the BD-tPor and PC71BM (0.31 eV) as compared to that between BD-pPor and PC71BM (0.36 eV). The low energy loss also leads to a higher value of open-circuit voltage for the BD-tPor based OSC than its BD-pPor counterpart, despite the slightly deeper HOMO energy level of BD-pPor. The enhanced values of Jsc and FF of the BD-tPor based OSCs may be related to the better exciton dissociation and charge transport, as confirmed from the PL spectra and charge carrier mobility. These results indicate that the combination of BODIPY, DPP and porphyrin in the same conjugate is very promising for small molecule organic solar cells.

Porphyrin Antenna-Enriched BODIPY–Thiophene Copolymer for Efficient Solar Cells

Low bandgap A-π-D copolymer, P(BdP-DEHT), consisting of alternating BOronDIPYrromethene (BODIPY) and thiophene units bridged by ethynyl linkers, and its porphyrin-enriched analogue, P(BdP/Por-DEHT), were prepared, and their optical and electrochemical properties were studied. P(BdP-DEHT) exhibits strong absorption in the 500-800 nm range with an optical bandgap of 1.74 eV. On the basis of cyclic voltammetry, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels are evaluated to be -5.40 and -3.66 eV, respectively. After the anchoring of zinc(II) porphyrin on the BODIPY unit, P(BdP/Por-DEHT) displays broadened absorption, thanks to porphyrins, and the optical bandgap decreases to 1.59 eV because of extension of BODIPY conjugation. The resulting estimated HOMO and LUMO energy levels, respectively, move to -5.32 and -3.73 eV. After optimization of the P(BdP-DEHT) or P(BdP/Por-DEHT) to PC71BM weight ratio to 1:2 in dichlorobenzene solution, the bulk heterojunction polymer solar cells show overall power conversion efficiencies (PCEs) of 3.03 and 3.86%, respectively. After solvent vapor annealing (SVA) treatment in CH2Cl2 for 40 s, the PCEs increased to 7.40% [Voc of 0.95 V, Jsc of 12.77 mA/cm2, and fill factor (FF) of 0.61 with energy loss of 0.79 eV] and 8.79% (Voc of 0.92 V, Jsc of 14.48 mA/cm2, and FF of 0.66 with energy loss of 0.67 eV). The increase in the PCE for P(BdP/Por-DEHT)-based devices is mainly attributed to the enhancement in Jsc and FF, which may be related to the broader absorption spectra, lower band gap, and better charge transport of P(BdP/Por-DEHT) compared to P(BdP-DEHT). This could also be related to the optimized nanoscale morphology of the active layer for both efficient exciton dissociation and charge transport toward the electrodes and a balanced charge transport in the device, induced by the SVA treatment of the active layer.

DNA structure-specific sensitization of a metalloporphyrin leads to an efficient in vitro quadruplex detection molecular tool

The search for convenient molecular probes for detecting DNA and RNA quadruplexes in vitro is marked by a rapid pace of progress, spurred on by the multiple roles these higher-order nucleic acid structures play in many genetic dysregulations. Here, we contribute to this search, reporting on a palladated porphyrin named Pd·TEGPy: its efficiency as quadruplex-selective fluorescent dye relies on a structural design that endows it with attractive supramolecular and electronic properties and makes it an efficient turn-on, quadruplex-selective fluorescent stain thanks to a DNA-mediated sensitization mechanism that ensures a high level of specificity.