7 research outputs found
Resolving the excited state relaxation dynamics of guanosine monomers and hydrogen-bonded homodimers in chloroform solution
Ultrafast vibrational dynamics of hydrogen-bonded base pairs and hydrated DNA
Diese Arbeit ermöglicht ein detailliertes VerstĂ€ndnis der Schwingungsdynamik und Kupplungen in einem Basenpaar-Modellsystem und in kĂŒnstlichen DNA-Oligomeren bei verschiedenen Hydratationsgraden. Durch die Verwendung von nichtlinearer ultraschneller IR Pump-Probe Spektroskopie sind die Schwingungsbewegungen hydratisierter DNA und die schnellsten VerĂ€nderungen in den DNA-Wasser-Wechselwirkungen und Hydrationsgeometrien direkt zugĂ€nglich. 2-pyridone/2-hydroxypyridine ist ein Modellsystem fĂŒr die gekoppelte intermolekularen WasserstoffbrĂŒcken, deren Struktur der von DNA-Basenpaaren Ă€hnelt. In Dichlormethan existiert das MolekĂŒl als ein zyklischer 2-Pyridon-Dimer, deren Vorkommern durch NMR-und 2D-FTIR Spektroskopie verifiziert wurde. Die beobachteten kohĂ€rente Oszillationen aufgrund niederfrequenter Wellenpaketbewegungen der Dimere können fĂŒr die Dynamik und rĂ€umliche Geometrie der Basenpaare in den DNA-MolekĂŒl relevant sein. Transiente Schwingungsspektren eines poly[d(A-T)]:poly[d(A-T)] Film erlauben die Zuordnung von verschiedenen NH-Streckbanden zu einer bestimmten Schwingung der Nukleinbasen und ermöglichen deren Abgrenzung zu den BeitrĂ€gen von OH-Streckschwingungen des umgebenden Wassers. Bei einem niedrigen Hydratisierungsgrad verĂ€ndern die restlichen, an die Phosphatgruppen gebundenen WassermolekĂŒle, ihre Ausrichtung auf ultraschnellen Zeitskalen nicht. Im Fall vollstĂ€ndig hydratisierter DNA ist die Dynamik der WasserhĂŒlle dem Verhalten des reinen Wassers Ă€hnlicher und man beobachtet spektrale Diffusion der OH-Streckschwingung im Subpikosekundenbereich sowie einen Zerfall der Schwingungsanisotropie durch MolekĂŒlrotation und/oder Energietransfer. Die WassermolekĂŒle der Phosphat-HydratationshĂŒlle dienen als effiziente WĂ€rmesenke fĂŒr Ăberschussenergie aus der DNA, wobei die Energietransferzeiten im fs-bereich liegen. Im Gegensatz dazu erfolgt Energietransport innerhalb der DNA auf einer langsameren Zeitskala von 20 ps.This thesis provides a detailed understanding of vibrational dynamics and couplings in a base pair model system and artificial DNA oligomers at different levels of hydration. By using nonlinear ultrafast infrared pump-probe spectroscopy, the basic vibrational motions of hydrated DNA and the fastest changes in the DNAâwater interactions and hydration geometries are directly accessed. 2-pyridone/2-hydroxypyridine is used as a model molecule for coupled intermolecular hydrogen bonds with a structure resembling a DNA base pair. In dichloromethane the molecule predominantly exists as a cyclic 2-pyridone dimer as determined using a combined NMR and 2D FTIR approach. The observed coherent oscillations due to low-frequency hydrogen bond wavepacket motions of the dimers are expected to be relevant for the dynamics and spatial geometry of base pairs in DNA molecule. Transient vibrational spectra of a poly[d(A-T)]:poly[d(A-T)] film enabled the assignment of different NH stretching bands to particular nucleobase vibrations, also discerning them from the OH stretching contributions of the surrounding water. At a low hydration level, residual water molecules, bound to the phosphate groups, do not alter their orientation on ultrafast time scales. In the case of fully hydrated DNA, the dynamics of the water shell are closer to those of bulk liquid water with a sub-picosecond spectral diffusion and a loss of vibrational anisotropy as a result of molecular rotation and/or energy transfer. The water shell around the phosphates serves as a efficient heat sink accepting excess energy from DNA in a femtosecond time domain, whereas the energy transfer within DNA occurs on the time scale of 20 ps
Note: An environmental cell for transient spectroscopy on solid samples in controlled atmospheres
A sample cell for performing time-resolved spectroscopy on solid samples within an atmosphere of controlled vapor composition was designed and constructed. Control over vapor composition was accomplished using a combination of passive sealing and chemical agents. Performance characteristics especially well-suited to studies using femtosecond mid-infrared spectroscopy were achieved by the use of ultrathin silicon nitride windows and a rapid and reproducible sample cell exchange mechanism. © 2013 American Institute of Physics
Diagnostic Performance of a Support Vector Machine for Dermatofluoroscopic Melanoma Recognition: The Results of the Retrospective Clinical Study on 214 Pigmented Skin Lesions
The need for diagnosing malignant melanoma in its earliest stages results in an increasing number of unnecessary excisions. Objective criteria beyond the visual inspection are needed to distinguish between benign and malignant melanocytic tumors in vivo. Fluorescence spectra collected during the prospective, multicenter observational study (“FLIMMA”) were retrospectively analyzed by the newly developed machine learning algorithm. The formalin-fixed paraffin-embedded (FFPE) tissue samples of 214 pigmented skin lesions (PSLs) from 144 patients were examined by two independent pathologists in addition to the first diagnosis from the FLIMMA study, resulting in three histopathological results per sample. The support vector machine classifier was trained on 17,918 fluorescence spectra from 49 lesions labeled as malignant (1) and benign (0) by three histopathologists. A scoring system that scales linearly with the number of the “malignant spectra” was designed to classify the lesion as malignant melanoma (score > 28) or non-melanoma (score ≤ 28). Finally, the scoring algorithm was validated on 165 lesions to ensure model prediction power and to estimate the diagnostic accuracy of dermatofluoroscopy in melanoma detection. The scoring algorithm revealed a sensitivity of 91.7% and a specificity of 83.0% in diagnosing malignant melanoma. Using additionally the image segmentation for normalization of lesions’ region of interest, a further improvement of sensitivity of 95.8% was achieved, with a corresponding specificity of 80.9%
Aqueous Solvation of Ammonia and Ammonium: Probing Hydrogen Bond Motifs with FT-IR and Soft X-ray Spectroscopy
In a multifaceted investigation combining local soft X-ray and vibrational spectroscopic probes with ab initio molecular dynamics simulations, hydrogen-bonding interactions of two key principal amine compounds in aqueous solution, ammonia (NH3) and ammonium ion (NH4+), are quantitatively assessed in terms of electronic structure, solvation structure, and dynamics. From the X-ray measurements and complementary determination of the IR-active hydrogen stretching and bending modes of NH3 and NH4+ in aqueous solution, the picture emerges of a comparatively strongly hydrogen-bonded NH4+ ion via NâH donating interactions, whereas NH3 has a strongly accepting hydrogen bond with one water molecule at the nitrogen lone pair but only weakly NâH donating hydrogen bonds. In contrast to the case of hydrogen bonding among solvent water molecules, we find that energy mismatch between occupied orbitals of both the solutes NH3 and NH4+ and the surrounding water prevents strong mixing between orbitals upon hydrogen bonding and, thus, inhibits substantial charge transfer between solute and solvent. A close inspection of the calculated unoccupied molecular orbitals, in conjunction with experimentally measured N K-edge absorption spectra, reveals the different nature of the electronic structural effects of these two key principal amine compounds imposed by hydrogen bonding to water, where a pH-dependent excitation energy appears to be an intrinsic property. These results provide a benchmark for hydrogen bonding of other nitrogen-containing acids and bases
Aqueous Solvation of Ammonia and Ammonium: Probing Hydrogen Bond Motifs with FT-IR and Soft Xâray Spectroscopy
In
a multifaceted investigation combining local soft X-ray and
vibrational spectroscopic probes with ab initio molecular dynamics
simulations, hydrogen-bonding interactions of two key principal amine
compounds in aqueous solution, ammonia (NH<sub>3</sub>) and ammonium
ion (NH<sub>4</sub><sup>+</sup>), are quantitatively assessed in terms
of electronic structure, solvation structure, and dynamics. From the
X-ray measurements and complementary determination of the IR-active
hydrogen stretching and bending modes of NH<sub>3</sub> and NH<sub>4</sub><sup>+</sup> in aqueous solution, the picture emerges of a
comparatively strongly hydrogen-bonded NH<sub>4</sub><sup>+</sup> ion
via NâH donating interactions, whereas NH<sub>3</sub> has a
strongly accepting hydrogen bond with one water molecule at the nitrogen
lone pair but only weakly NâH donating hydrogen bonds. In contrast
to the case of hydrogen bonding among solvent water molecules, we
find that energy mismatch between occupied orbitals of both the solutes
NH<sub>3</sub> and NH<sub>4</sub><sup>+</sup> and the surrounding
water prevents strong mixing between orbitals upon hydrogen bonding
and, thus, inhibits substantial charge transfer between solute and
solvent. A close inspection of the calculated unoccupied molecular
orbitals, in conjunction with experimentally measured N K-edge absorption
spectra, reveals the different nature of the electronic structural
effects of these two key principal amine compounds imposed by hydrogen
bonding to water, where a pH-dependent excitation energy appears to
be an intrinsic property. These results provide a benchmark for hydrogen
bonding of other nitrogen-containing acids and bases