Development of a Nanoscale-Sensitive DNA Sensor using Functionalized Graphene Substrates and Fluorescence Lifetime Characterization

Fluorescence Lifetime Image Microscopy (FLIM) of nanostructured graphene substrates was used to measure the recently observed nanoscale distance-scaling of the fluorescence lifetime of dyes located in the vicinity of graphene sheets, at distances up to about 30 nm. The results were compared with a Resonant Energy Transfer (RET) theoretical model and used to establish an experimental fluorescence lifetime-to-nanoscale distance conversion function. In the following, this nano-optical relation was used for the design of a Deoxyribonucleic Acid (DNA) biosensor. Graphene was functionalized with fluorescently labeled DNA molecular beacons that unfold during hybridization with complementary DNA, and thereby change the distance of the fluorescent dye from the graphene surface. The spatial distribution of DNA molecular beacons binding to the surface of a graphene flake was studied, as well as the temporal kinetics of the hybridization reaction using time-lapse FLIM measurements. The results showed a vertical ascent of a fluorescent label relative to the graphene surface with a distance extension that is in accordance with the expected molecular length of the specific DNA sequence used. Interestingly, an intermediate state associated to a distance of a few nanometers was identified with a lifespan of about 85 minutes. The developed graphene-based DNA sensor was shown to enable optical detection of nanoscale distances in liquid media. These findings indicate that the fluorescence lifetime-based detection coupled with nanoscale interaction effects may find applications in various biosensing applications such as health and food-quality tracing. For the processing of FLIM data, several fluorescence lifetime calculation algorithms were compared and integrated into a specially designed and implemented analysis software toolbox in MATLAB.Imagens de Microscopia de Tempo de Vida de Fluorescência (FLIM) de substratos de grafeno nano-estruturados foram usadas para a medição da recentemente observada alteração do tempo de vida de fluorescência de corantes quando localizados na vizinhança de grafeno para distâncias até cerca de 30 nm. Os resultados foram comparados com um modelo teórico de Transferência Ressonante de Energia (RET) e utilizados para o estabelecimento de uma função de calibração experimental entre tempo de vida de fluorescência e distâncias à nano-escala. Posteriormente, esta relação nano-ótica foi utilizada para o desenvolvimento de um biossensor de Ácido Desoxirribonucleico (ADN). Substratos de grafeno foram funcionalizados com sinais moleculares (molecular beacons) de ADN que se desdobram durante a hibridização com ADN complementar, alterando a distância do corante fluorescente à superfície de grafeno. A distribuição espacial da ligação de sinais moleculares de ADN à superfície do grafeno foi estudada, bem como a cinética de reação de hibridização, usando medições de FLIM por lapso de tempo. Os resultados mostraram a ascensão vertical dos marcadores fluorescentes relativamente à superfície, com uma deslocamento total que está de acordo com o comprimento molecular esperado para a sequência de ADN utilizada. Curiosamente, um estado intermedio associado a uma distância de alguns nanómetros foi identificado, tendo este uma duração de cerca de 85 minutos. Foi então demonstrado que o sensor de ADN desenvolvido permite a deteção ótica de distâncias à nano-escala em meio líquido. Estes resultados indicaram que a deteção baseada em tempo de vida de fluorescência, acoplada aos efeitos desta interação ótica à nano-escala pode ser utilizada em várias aplicações de biodeteção, tal como na saúde e no rastreamento da qualidade alimentar. Para o tratamento de dados de FLIM, vários algoritmos de cálculo de tempo de vida foram comparados e integrados num programa de análise especificamente desenhado e implementado para o efeito, em ambiente MATLAB.International Iberian Nanotechnology Laboratory – IN

On Heteroaromaticity Of Nucleobases. Bond Lengths As Multidimensional Phenomena

Three hundred and nine carbon-carbon, carbon-nitrogen, and carbon-oxygen w-bond lengths in high precision crystal structures of 31 purine and pyrimidine nucleobases were related to the Pauling w-bond order, its analogues corrected to crystal packing effects, the numbers of non-hydrogen atoms around the bond, and the sum of atomic numbers of the bond atoms. Principal Component Analysis (PCA) and Hierachical Cluster Analysis (HCA) demonstrated that the bond lengths in the nucleobases are three-dimensional phenomenon, characterized by nine distinct classes of bonds. Bond lengths predicted by Linear Regression models, Pauling Harmonic Potential Curves, Multiple Linear Regression, Principal Component, and Partial Least Squares Regression were compared to those calculated by molecular mechanics, semiempirical, and ab initio methods using PCA-HCA procedure on the calculated bond lengths, statistical parameters, and structural aromaticity indices. Incorporation of crystal packing effects into bond orders makes multivariate models to be competitive to semiempirical results, while further improvement of quantum chemical calculations can be achieved by geometry optimization of molecular clusters.433787809Hurst, D.T., (1980) An Introduction to the Chemistry and Biochemistry of Pyrimidines, Purines and Pteridines, p. 104. , Wiley: Chichester. UKChaudhuri, N.C., Ren, R.X.-F., Kool, E.T., C-nucleosides derived from simple aromatic hydrocarbons (1997) Synlett, pp. 341-347Saenger, W., (1984) Principles of Nucleic Acid Structure, , Springer: New YorkBarciszewski, J., Barciszewska, M.Z., Siboska, G., Rattan, S.I.S., Clark, B.F.C., Some unusual nucleic acid bases are products of hydroxyl radical oxidation of DNA and RNA (1999) Mol. Biol. Rep., 26, pp. 231-238Ray, A., Norden, B., Peptide nucleic acid (PNA): Its medical and biotechnical applications and promise for the future (2000) Faseb J., 14, pp. 1041-1060Barnes T.W. 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Lett., 2, pp. 1415-1418Clowney, L., Jain, S.C., Srinivasan, A.R., Westbrook, J., Olson, W.K., Berman, H.M., Geometric parameters in nucleic acids: Nitrogenous bases (1996) J. Am. Chem. Soc., 118, pp. 509-518Berman, H.M., Olson, W.K., Beveridge, D.L., Westbrook, J., Gelbin, A., Demeny, T., Hsieh, S.H., Schneider, B., The nucleic-acid database: A comprehensive relational database of 3-dimensional structures of nucleic-acids (2000) Biophys. J., 63, pp. 751-759. , http://ndbserver.rutgers.edu/structure-finder/ndb/, Website: The Nucleic Acid Database. The Nucleic Acid Database Project. 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Design Autom. News, 8, pp. 31-37. , http://www.ccdc.cam.ac.uk/prods/csd/osd.html, Website: The Cambridge Structural Database. University of Cambridge, Cambridge, UKGuckian, K.M., Schweitzer, B.A., Ren, R.X.-F., Sheils, C.J., Paris, P.L., Tahmassebi, D.C., Kook, E.T., Experimental measurement of aromatic stacking affinities in the context of duplex DNA (1996) J. Am. Chem. Soc., 118, pp. 8182-8183Guckian, K.M., Schweitzer, B.A., Ren, R.X.-F., Sheils, C.J., Paris, P.L., Tahmassebi, D.C., Kook, E.T., Factors contributing to aromatic stacking in water: Evaluation in the context of DNA (2000) J. Am. Chem. Soc., 118, pp. 2213-2222Voet, D., Voet, J.G., (1995) Biochemistry, 2nd Ed., p. 868. , J. Wiley: New YorkLemieux, S., Oldziej, S., Major, F., Nucleic acids: Qualitative modeling (1998) Encyclopedia of Computational Chemistry, 3, pp. 1930-1941. , von Ragué Schleyer, P., Ed.Wiley: Chichester, UKVan der Waals Volumes Bondi, A., Radii, (1964) J. Phys. 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Structure of 5,6-dimethylphenanthridinium triflate, [N-(6-Phenanthridinyl-methyl)-aza-18-crown-6-κ5O,O′,O ″,O‴,O″″](picrate-κ2O,O′)potassi um, and [N,N′-Bis(6-phenanthridinyl-κN-methyl)-7 (1996) Acta Crystallogr., B52, pp. 823-837Kiralj, R., Kojić-Prodić, B., Nikolić, S., Trinajstić, N., Bond lengths and bond orders in benzenoid hydrocarbons and related systems: A comparison of valence bond and molecular orbital treatments (1998) J. Mol. Struct. 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Organophosphorus Chemistry 2018

Organophosphorus chemistry is an important discipline within organic chemistry. Phosphorus compounds, such as phosphines, trialkyl phosphites, phosphine oxides (chalcogenides), phosphonates, phosphinates and >P(O)H species, etc., may be important starting materials or intermediates in syntheses. Let us mention the Wittig reaction and the related transformations, the Arbuzov- and the Pudovik reactions, the Kabachnik–Fields condensation, the Hirao reaction, the Mitsunobu reaction, etc. Other reactions, e.g., homogeneous catalytic transformations or C-C coupling reactions involve P-ligands in transition metal (Pt, Pd, etc.) complex catalysts. The synthesis of chiral organophosphorus compounds means a continuous challenge. Methods have been elaborated for the resolution of tertiary phosphine oxides and for stereoselective organophosphorus transformations. P-heterocyclic compounds, including aromatic and bridged derivatives, P-functionalized macrocycles, dendrimers and low coordinated P-fragments, are also of interest. An important segment of organophosphorus chemistry is the pool of biologically-active compounds that are searched and used as drugs, or as plant-protecting agents. The natural analogue of P-compounds may also be mentioned. Many new phosphine oxides, phosphinates, phosphonates and phosphoric esters have been described, which may find application on a broad scale. Phase transfer catalysis, ionic liquids and detergents also have connections to phosphorus chemistry. Green chemical aspects of organophosphorus chemistry (e.g., microwave-assisted syntheses, solvent-free accomplishments, optimizations, and atom-efficient syntheses) represent a dynamically developing field. Last, but not least, theoretical approaches and computational chemistry are also a strong sub-discipline within organophosphorus chemistry

Conformational Study Of (8α,8′β)-bis(substituted Phenyl)-lignano-9,9'-lactones By Means Of Combined Computational, Database Mining, Nmr, And Chemometric Approaches

β-(3,4-Methylenedioxybenzyl)-γ-butyrolactone (MDBL) and (-)-hinokinin (HK) were obtained by partial synthesis and characterized by 1H NMR and computational methods (conformational analysis, molecular modeling, structural data mining and chemometrics). Three conformers were detected for MDBL and nine were found for HK. The energy differences are around 1 and 2 kcal mol-1 and rotation barriers are less than 3 and 5 kcal mol-1 for MDBL and HK conformers, respectively. The geometries of these conformers, obtained from semiempirical PM3 and density functional theory (DFT) B3LYP 6-3IG** calculations agree satisfactorily with 1H NMR data (vicinal proton-proton coupling constants) and structures retrieved from the Cambridge Structural Database (torsion angles). DFT combined with some variants of the Haasnoot-de Leeuuw-Altona equations gives the best predictions for the coupling constants. The molecular conformation of MDBL, of HK, and of related systems depends not only on intramolecular interactions but also on crystal packing forces and solvent-solute interactions, in particular hydrogen bonds and polar interactions. Hydration favors more stable HK conformers, which can be important for their behavior in chemical and biological systems. © 2007 American Chemical Society.1112863166333McRae, W.D., Towers, G.H.N., Biological Activities of Lignans (1984) Phytochemistry, 23, pp. 1207-1220Ayres, D.C., Loike, J.D., (1990) Chemistry and Pharmacology of Natural Products: LignansChemical, Biological and Clinical Properties, , Cambridge University Press: New YorkWard, R.S., Lignans, Neolignans, and Related Compounds (1993) Nat. Prod. Rep, 10, pp. 1-28Ward, R.S., Lignans, Neolignans, and Related Compounds (1995) Nat. Prod. Rep, 12, pp. 183-205Ward, R.S., Lignans, Neolignans, and Related Compounds (1997) Nat. 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