Dendritic molecular assemblies for singlet oxygen generation: meso-tetraphenylporphyrin-based biphotonic sensitizers with remarkable luminescence

International audienceFour new TPP-based chromophores (1-4) peripherally functionalized with dendrons contg. 2-fluorenyl groups were studied for their potential to serve in photodynamic therapy. Their linear and nonlinear optical properties were investigated. With significant TPA cross-sections at 790 nm, good singlet oxygen generation capabilities and relatively large intrinsic fluorescence, sensitizers such as 1 might become particularly appealing for theranostics

Stimulated emission depletion and fluorescence correlation spectroscopy of a branched quadrupolar chromophore

Stimulated emission depletion (STED) and single molecule fluorescence correlation spectroscopy (FCS) are used to determine stimulated emission cross-sections and investigate non-radiative relaxation in a branched quadrupolar chromophore (OM77). The results are used as inputs to simulations of single molecule STED by which the feasibility of STED control of the single molecule fluorescence cycle call be assessed. Single molecule STED in OM77 is shown to be readily achievable; however its effectiveness in reducing triplet trapping is apparently mediated by fast non-radiative relaxation processes other than intersystem crossing and rapid quenching of the triplet state in a non-deoxygenated environment

Nonlinear optical properties of meso-Tetra(fluorenyl)porphyrins peripherally functionalized with one to four ruthenium alkynyl substituents

The synthesis of a series of four porphyrin derivatives based on a meso-tetrafluorenylporphyrin core functionalized with one to four trans-chlorobis(dppe)ruthenium alkynyl units (dppe = 1,2-bis(diphenylphosphino)ethane) at the periphery, together with cyclic voltammetry (CV) and UV–Vis absorption and emission spectroscopy studies, are reported. In these multipolar assemblies, the organoruthenium endgroups are potential electron-donors and the central porphyrin core is a potential electron-acceptor. The third-order nonlinear optical (NLO) responses have been assessed by Z-scan, revealing that these extended π-networks incorporating polarizable organometallic units behave as nonlinear absorbers in the near-IR range. The role of the peripheral transition metal centers on the third-order NLO properties is discussed

Stimulated emission depletion dynamics in push-push polyenes

Two-photon fluorescence polarisation and stimulated emission depletion dynamics are investigated in three high two -photon cross-section push-push polyenes: OM62, LP79 and OM77 and compared to the behaviour of a standard fluorophore (rhodamine 6G). Two-photon fluorescence anisotropy measurements (R(O) and Omega) were undertaken using picosecond time-correlated single photon counting (TCSPC). For OM62 and LP79 these are consistent with a diagonal two-dimensional transition tensor with S-XX>S-YY. For OM77 the contribution of off-diagonal elements (S-XY & S-YX) appears significant. Two-photon fluorescence anisotropy decay data is combined with streak camera measurements of excited state population depletion to determine stimulated emission cross sections and ground state vibrational relaxation times. Cross-sections for STED in all three polyenes were found to be significantly higher than those for rhodamine 6G. The efficiency of STED is however dependent on the degree to which the S-1-->S-0 transition is saturated by the DUMP pulse; this is mediated by fast ground state vibrational relaxation. Of the three polyenes.. LP79 is seen to combine a large stimulated emission cross-section (c.a. 13sigma(r6G)) with rapid ground state relaxation (tau(R)=240fs)

Limited Lifespan of Fragile Regions in Mammalian Evolution

An important question in genome evolution is whether there exist fragile regions (rearrangement hotspots) where chromosomal rearrangements are happening over and over again. Although nearly all recent studies supported the existence of fragile regions in mammalian genomes, the most comprehensive phylogenomic study of mammals (Ma et al. (2006) Genome Research 16, 1557-1565) raised some doubts about their existence. We demonstrate that fragile regions are subject to a "birth and death" process, implying that fragility has limited evolutionary lifespan. This finding implies that fragile regions migrate to different locations in different mammals, explaining why there exist only a few chromosomal breakpoints shared between different lineages. The birth and death of fragile regions phenomenon reinforces the hypothesis that rearrangements are promoted by matching segmental duplications and suggests putative locations of the currently active fragile regions in the human genome

Combining Computational Prediction of Cis-Regulatory Elements with a New Enhancer Assay to Efficiently Label Neuronal Structures in the Medaka Fish

The developing vertebrate nervous system contains a remarkable array of neural cells organized into complex, evolutionarily conserved structures. The labeling of living cells in these structures is key for the understanding of brain development and function, yet the generation of stable lines expressing reporter genes in specific spatio-temporal patterns remains a limiting step. In this study we present a fast and reliable pipeline to efficiently generate a set of stable lines expressing a reporter gene in multiple neuronal structures in the developing nervous system in medaka. The pipeline combines both the accurate computational genome-wide prediction of neuronal specific cis-regulatory modules (CRMs) and a newly developed experimental setup to rapidly obtain transgenic lines in a cost-effective and highly reproducible manner. 95% of the CRMs tested in our experimental setup show enhancer activity in various and numerous neuronal structures belonging to all major brain subdivisions. This pipeline represents a significant step towards the dissection of embryonic neuronal development in vertebrates