Vibronic coupling and ultrafast electron transfer studied by picosecond time-resolved resonance Raman and CARS spectroscopy

Diese Arbeit befasst sich mit der vibronischen Kopplung zweier angeregter Elektronenniveaus in Diphenylhexatrien (DPH) und mit der Rolle von Schwingungsmoden beim ultraschnellen photoinduzierten intramolekularen Elektronentransfer in Betain-30. Mit Hilfe von Pikosekunden-zeitaufgelöster Kohärenter Antistokes Ramanspektroskopie im angeregten Zustand des DPH haben wir zum ersten Mal das Auftreten zweier extrem frequenzverbreiterter Ramanlinien beobachtet, die gegenüber dem C=C Streckschwingungsbereich zu höheren Wellenzahlen verschoben sind. Beide Ramanlinien lassen sich mit Erhöhung der Lösungsmittelpolarisierbarkeit um mehr als 50 cm-1 in Richtung niedrigerer Frequenzen verschieben. Zur Erklärung des Sachverhalts werden zwei Modelle diskutiert: (i) die Existenz zweier Isomere im ersten angeregten Elektronenniveau des DPH und (ii) vibronische Kopplung der beiden Elektronenniveaus durch eine niederfrequente asymmetrische bu Schwingungsbewegung (pseudo-Jahn-Teller Effekt). Mit Hilfe von stationärer Ramanspektroskopie und insbesondere Messungen der Stokes- und anti-Stokes-Ramanspektren mit Pikosekunden-Zeitauflösung, die Beteiligung von Molekülschwingungen beim Elektronentransfer in Betain-30 wurde untersucht. Zum ersten Mal wurde eine modenspezifische Kinetik der Ramanaktiven Schwingungen nach Elektronen Rücktransfer in Betain-30 beobachtet. Die hochfrequenten Ramanaktiven Moden werden beim Elektronen Rücktransfer bevorzugt, was zu einer nicht-thermischen Besetzung der Schwingungen führt. Das ist zumindest qualitativ in Übereinstimmung mit Rechnungen die auf Fermi's Goldener Regel basieren. Eine Thermalisierung zwischen den beobachteten Ramanaktiven Moden stellt sich frühestens 10 ps nach Anregung ein. Die Thermalisierung in dem gesamten Molekül ist aber noch nicht beendet.This thesis deals with vibronic coupling effects between two excited electronic singlet states in Diphenylhexatriene (DPH), and with the role of vibrational modes in photoinduced ultrafast electron transfer in Betaine-30. By using the picosecond time-resolved Coherent Antistokes Raman Spectroscopy method, it was possible to observe for the first time two very broad and unusual up-shifted vibrational frequencies in the excited singlet state of DPH, which have frequencies higher than frequency region of the C=C stretching mode. These two frequencies shift towards lower frequencies with increasing solvent polarizability. Two explanations have been discussed: (i) the simultaneous existence of two rotamers, where the two frequencies originate from "different molecules" and (ii) a model of vibronic coupling by an asymmetric low frequency bu-mode (pseudo-Jahn-Teller effect). By using the picosecond time-resolved anti-Stokes Raman spectroscopy method, we observed for the first time mode-specific excitation of vibrational modes after back-electron transfer in Betaine-30. In the primary event, high frequency Raman active modes are most effective in accepting energy, which leads to a non-thermal distribution of the relative populations of Raman active modes. This is qualitatively in accordance with predictions derived from Fermi's Golden Rule. Although energy transfer between the Raman active modes has been finished after about 10 to 15 ps, thermalization is not yet complete in the whole molecule

Autonomic Innervation and Segmental Muscular Disconnections at the Human Pulmonary Vein-Atrial Junction Implications for Catheter Ablation of Atrial-Pulmonary Vein Junction

ObjectivesThis study sought to examine the muscle connections and autonomic nerve distributions at the human pulmonary vein (PV)-left atrium (LA) junction.BackgroundOne approach to catheter ablation of atrial fibrillation (AF) is to isolate PV muscle sleeves from the LA. Elimination of vagal response further improves success rates.MethodsWe performed immunohistochemical staining on 192 circumferential venoatrial segments (32 veins) harvested from 8 autopsied human hearts using antibodies to tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT).ResultsMuscular discontinuities of widths 0.1 to 5.5 mm (1.1 ± 1.0 mm) and abrupt 90° changes in fiber orientation were found in 70 of 192 (36%) and 36 of 192 (19%) of PV-LA junctions, respectively. Although these anisotropic features were more common in the anterosuperior junction (p < 0.01), they were also present around the entire PV-LA junction. Autonomic nerve density was highest in the anterosuperior segments of both superior veins (p < 0.05 versus posteroinferior) and inferior segments of both inferior veins (p < 0.05 vs. superior), highest in the LA within 5 mm of the PV-LA junction (p < 0.01), and higher in the epicardium than endocardium (p < 0.01). Adrenergic and cholinergic nerves were highly co-located at tissue and cellular levels. A significant proportion (30%) of ganglion cells expressed dual adrenocholinergic phenotypes.ConclusionsMuscular discontinuities and abrupt fiber orientation changes are present in >50% of PV-LA segments, creating significant substrates for re-entry. Adrenergic and cholinergic nerves have highest densities within 5 mm of the PV-LA junction, but are highly co-located, indicating that it is impossible to selectively target either vagal or sympathetic nerves during ablation procedures

Novel theranostic nanoporphyrins for photodynamic diagnosis and trimodal therapy for bladder cancer

The overall prognosis of bladder cancer has not been improved over the last 30 years and therefore, there is a great medical need to develop novel diagnosis and therapy approaches for bladder cancer. We developed a multifunctional nanoporphyrin platform that was coated with a bladder cancer-specific ligand named PLZ4. PLZ4-nanoporphyrin (PNP) integrates photodynamic diagnosis, image-guided photodynamic therapy, photothermal therapy and targeted chemotherapy in a single procedure. PNPs are spherical, relatively small (around 23&nbsp;nm), and have the ability to preferably emit fluorescence/heat/reactive oxygen species upon illumination with near infrared light. Doxorubicin (DOX) loaded PNPs possess slower drug release and dramatically longer systemic circulation time compared to free DOX. The fluorescence signal of PNPs efficiently and selectively increased in bladder cancer cells but not normal urothelial cells in&nbsp;vitro and in an orthotopic patient derived bladder cancer xenograft (PDX) models, indicating their great potential for photodynamic diagnosis. Photodynamic therapy with PNPs was significantly more potent than 5-aminolevulinic acid, and eliminated orthotopic PDX bladder cancers after intravesical treatment. Image-guided photodynamic and photothermal therapies synergized with targeted chemotherapy of DOX and significantly prolonged overall survival of mice carrying PDXs. In conclusion, this uniquely engineered targeting PNP selectively targeted tumor cells for photodynamic diagnosis, and served as effective triple-modality (photodynamic/photothermal/chemo) therapeutic agents against bladder cancers. This platform can be easily adapted to individualized medicine in a clinical setting and has tremendous potential to improve the management of bladder cancer in the clinic

Signal generation and Raman-resonant imaging by non-degenerate four-wave mixing under tight focusing conditions

Weeks T, Schie I, Wachsmann-Hogiu S, Huser T. Signal generation and Raman-resonant imaging by non-degenerate four-wave mixing under tight focusing conditions. J. Biophoton. 2010;3(3):169-175

The effects of structural and microenvironmental disorder on the electronic properties of poly[2-methoxy,5-(2 '-ethyl-hexoxy)-1,4-phenylene vinylene] (MEH-PPV) and related oligomers

In this study, electroabsorption (Stark) spectroscopy is used to determine the trace of the change in polarizability (tr (Delta x) over bar) and the absolute value of the change in dipole moment (/Delta(mu) over right arrow/) of the electroluminescent polymer poly [2-methoxy,5-(2'-ethyl-hexoxy)- 1,4-phenylene vinylene] (MEH-PPV) and several model oligomers in L solvent glass matrixes. We find a value of tr (Delta alpha) over left right arrow of similar to2000 Angstrom(3) for the polymer and for a 9-ring substituted oligomer in both toluene and 2-methyl tetrahydrofuran matrixes at 77 K with smaller values being obtained for 3- and 5-ring unsubstituted oligomers. Although gas-phase calculations of tr /(Delta alpha) over left right arrow/. using INDO/SCI yield values that are about a factor of 8 smaller than the experiment, excellent agreement is obtained when the effects of solid-state dielectric screening are included. Screening increases tr /(Delta x) over left right arrow/ by bringing the energy gap between the 1B(u) and mA(g) states into agreement with solid-state measurements. Substantial values of /Delta(mu) over right arrow/ are observed experimentally both for the polymer and for the oligomers (6-11 D). Because in a planar (C-2h) geometry the oligomer and polymer are centrosymmetric, the observed /Delta(mu) over bar/ is an indication of disorder-induced symmetry breaking in the material. Calculations indicate that disorder in the ground-state geometry of the polymer (inner-sphere disorder) can account for nearly half of the observed /Delta(mu) over right arrow/. Disorder in the glassy environment (outer-sphere disorder) leads to a nonuniform electrostatic environment, and calculations show that this is a substantial contributor, accounting for the remainder of the observed /Delta(mu) over right arrow/

Label-free SERS analysis of proteins and exosomes with large-scale substrates from recordable compact disks

[EN] A central aspect to fully reach the biosensing scope of plasmonics beyond the research environment is its implementation in inexpensive and homogeneous functional nanostructured materials that can be manufactured in a large-scale fashion. Herein, we study the capabilities of consumer-grade compact disk technology for label-free SERS analysis of complex biological targets. Substrates from regular recordable disks (CD-R and DVD-R) coated with silver exhibit significant Raman enhancement. The magnitude of this enhancement depends on the nanostructure on the polycarbonate substrate, the silver thickness, and the excitation wavelength. The Raman fingerprint of hemoglobin and exosome samples were experimentally obtained in label-free conditions, which demonstrates the biosensing potential of this approach and suggests prospective developments towards fully exploiting the bioanalytical capabilities of SERS in point-of-care settings. (C) 2017 Elsevier B.V. All rights reserved.This work was supported by the Spanish Ministry of Economy and Competitiveness (CTQ2013-45875-R), FEDER, and the Generalitat Valenciana (PROMETEO II/2014/040). S.W-H would like to acknowledge financial support from UCDavis Office of Research. M.A-O also acknowledges the FPI program of the Spanish Ministry of Economy and Competitiveness for a PhD and an EEBB grant. We would like to thank Dr. Randy P. Carney for the exosome samples.Avella-Oliver, M.; Puchades, R.; Wachsmann-Hogiu, S.; Maquieira Catala, Á. (2017). Label-free SERS analysis of proteins and exosomes with large-scale substrates from recordable compact disks. Sensors and Actuators B Chemical. 252:657-662. https://doi.org/10.1016/j.snb.2017.06.058S65766225

Nanoconjugates of poly(malic acid) with functional modules for drug delivery

Nanoconjugates of β-poly(L-malic acid) (PMLA) have been synthesized with modules active in drug delivery, drug release, blocking of tumor-affiliated mRNA by antisense oligonucleotides, penetration of blood and cellular barriers, tissue targeting, membrane permeation, fluorescence, and protection. PMLA of microbial origin is non-toxic, nonimmunogenic, biodegradable and highly suited as a scaffold for tailored nanoconjugate chemistry. The nanoconjugate of 550 kDa allowed fluorescence imaging of brain tumor and breast cancer implanted on mouse, targeted on the basis of tumor tissue-inherent enhanced permeability and retention (EPR) and antibody recognition. The nanoconjugates were designed to inhibit tumor growth by preventing angiogenesis

Novel theranostic nanoporphyrins for photodynamic diagnosis and trimodal therapy for bladder cancer.

The overall prognosis of bladder cancer has not been improved over the last 30 years and therefore, there is a great medical need to develop novel diagnosis and therapy approaches for bladder cancer. We developed a multifunctional nanoporphyrin platform that was coated with a bladder cancer-specific ligand named PLZ4. PLZ4-nanoporphyrin (PNP) integrates photodynamic diagnosis, image-guided photodynamic therapy, photothermal therapy and targeted chemotherapy in a single procedure. PNPs are spherical, relatively small (around 23&nbsp;nm), and have the ability to preferably emit fluorescence/heat/reactive oxygen species upon illumination with near infrared light. Doxorubicin (DOX) loaded PNPs possess slower drug release and dramatically longer systemic circulation time compared to free DOX. The fluorescence signal of PNPs efficiently and selectively increased in bladder cancer cells but not normal urothelial cells in&nbsp;vitro and in an orthotopic patient derived bladder cancer xenograft (PDX) models, indicating their great potential for photodynamic diagnosis. Photodynamic therapy with PNPs was significantly more potent than 5-aminolevulinic acid, and eliminated orthotopic PDX bladder cancers after intravesical treatment. Image-guided photodynamic and photothermal therapies synergized with targeted chemotherapy of DOX and significantly prolonged overall survival of mice carrying PDXs. In conclusion, this uniquely engineered targeting PNP selectively targeted tumor cells for photodynamic diagnosis, and served as effective triple-modality (photodynamic/photothermal/chemo) therapeutic agents against bladder cancers. This platform can be easily adapted to individualized medicine in a clinical setting and has tremendous potential to improve the management of bladder cancer in the clinic