Application of computational quantum chemistry to chemical processes involved in mass spectrometry

The field of application of mass spectrometry (MS) has increased considerably due to the development of ionization techniques. Other factors that have stimulated the use of MS are the tandem mass spectrometry (MS/MS) and sequential mass spectrometry (MSn) techniques. However, the interpretation of the MS/MS and MSn data may lead to speculative conclusions. Thus, various quantum chemical methods have been applied for obtaining high quality thermochemical data in gas phase. In this review, we show some applications of computational quantum chemistry to understand the formation and fragmentation of gaseous ions of organic compounds in a MS analysis.Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)FAPESPCNP

A Fragmentation study of di-acidic mycosporine-like amino acids in electrospray and nanospray mass spectrometry

Two mycosporine (MAAs), containing an extra acid function, were analyzed by nanospray and electrospray ionization tandem mass spectrometry. In contrast to the previous studies it is demonstrated that no significant characteristic methyl radical loss occurred in positive mode. The fragmentation pathway in negative mode was also proposed in this work, along with theoretical calculations to characterize the site of protonation.No presente estudo, duas micosporinas (MAAs) contendo um segundo ácido carboxílico foram submetidas à fragmentação em eletrospray e nanospray em diferentes equipamentos. Em contraste com resultados anteriores, a eliminação de radical metila no modo positivo de análise foi um processo minoritário de fragmentação. Neste trabalho apresentamos também a via de fragmentação destas substâncias em modo negativo e cálculos teóricos para caracterizar os sítios de protonação.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Fragmentation study of di-acidic mycosporine-like amino acids in electrospray and nanospray mass spectrometry

No presente estudo, duas micosporinas (MAAs) contendo um segundo ácido carboxílico foram submetidas à fragmentação em eletrospray e nanospray em diferentes equipamentos. Em contraste com resultados anteriores, a eliminação de radical metila no modo positivo de análise foi um processo minoritário de fragmentação. Neste trabalho apresentamos também a via de fragmentação destas substâncias em modo negativo e cálculos teóricos para caracterizar os sítios de protonação. Two mycosporine (MAAs), containing an extra acid function, were analyzed by nanospray and electrospray ionization tandem mass spectrometry. In contrast to the previous studies it is demonstrated that no significant characteristic methyl radical loss occurred in positive mode. The fragmentation pathway in negative mode was also proposed in this work, along with theoretical calculations to characterize the site of protonation. Keywords: mycosporine, nanoESI-MS/MS, ESI-MS/MS, natural products, algae Introduction Mycosporine-like amino acids (MAAs) are a group of chemically related, water soluble compounds responsible for UV photoprotection in a diverse range of organisms including invertebrates, fish, bacteria, cyanobacteria, micro-and macroalgae. 1-3 These compounds are chemically characterised by the presence of either a cyclohexenone or cyclohexenimine chromophore conjugated with a substituent nitrogen of an amino acid, amino alcohol or amino group 1 MAAs normally show a strong UV absorption between 310 and 360 nm with high molar extinction coefficients. These characteristics indicate a possible photoprotective role that has been demonstrated in a number of studies 11-13 17 In the last few years, nanospray ionisation (nanoESI) is beginning to increase in importance, especially with the development of automated systems using 'chips' (arrays of uniform nanospray needles that are used only once to avoid contamination). 21 NanoESI offers the possibility of improved sensitivity and lower sample consumption over conventional ESI for the analysis of natural products. 22 This is especially important for the study of extracts from biological and medicinal sources when often only a very small amount of material is available. In 'chip based' nanoESI, the analyte solution is sprayed from a conducting pipette tip pressed against the rear of a chip using a small gas pressure and much lower voltages to create the spray. Recently, analysis of some natural antioxidants (retinoids Experimental Chemicals All solvents used were HPLC grade (Tedia, J. Baker and Fisher). Water was purified using a Milli-Q system (Millipore, Bedford, MA, USA). Trifluoroacetic acid (99.9%) was purchased from Aldrich. Galena Química e Farmacêutica Ltda/Brazil kindly supplied the standards of shinorine and porphyra-334 (product Helioguard ® 365-Porphyra umbilicalis extracts) Instrumentation Nanospray ionisation analyses were performed on two quadrupole-time of flight hybrid instruments: (a) an UltrOTOF-Q (Bruker Daltonics, Billerica, MA) using Tip™ Emittek (glass tip capillaries working with 500 V) or (b) a QStar-XL (Applied Biosystems, Warrington, UK) using a Nanomate HD automatic 'chip based' nanospray system (Advion Biosciences, Norwich, UK). The Nanomate was set for 5 µL of solution to be aspirated and sprayed through a Nanomate 400 chip at 1.45 kV, with a nitrogen back pressure of 0.4 psi. On both instruments, the ion source gas and curtain gas were nitrogen. Electrospray ionisation analyses were performed on five instruments: (a) an Apex 4 7.0 Tesla Fouriertransform ion-cyclotron resonance mass spectrometer (Bruker Daltonics, Billerica, MA, USA). Samples were directly infused into the Apollo electrospray source from a syringe pump at 100 µL h -1 . Analyses were performed at a capillary voltage, of 4600V and capillary exit potential of 200 V (except were indicated otherwise). The N 2 drying gas temperature was 200 °C. A mixture of PEG grades was used as an external calibrant for accurate-mass ESI analysis; (b) on a quadrupole-time of flight instrument (UltrOTOF-Q, Bruker Daltonics, Billerica, MA). The analyses were performed in positive ion ESI mode at a capillary voltage of 3400 V and N 2 drying gas temperature of 180 °C. NaTFA 10 mmol L -1 was used as a standard for internal and external calibration; (c) on a QStar-XL quadrupole-time-of-flight instrument (Applied Biosystems, Warrington, UK); (d) on a Quattro-LC triple quadrupole mass spectrometer (Micromass, Manchester, UK); (e) on an Esquire HCT ion trap instrument (Bruker Daltonics, Billerica, MA, USA) using a syringe pump (Cole-Parmer, Vernon Hills, IL, USA). Ion trap analyses were performed using nitrogen as the nebulising and drying gas and helium as the bath gas (4×10 -6 mbar). Theoretical calculations All calculations were performed in Gaussian 03 27 suite of programs using the B3LYP/6-31+G(d,p) model. 28,29 The geometries of neutral and protonated species were optimised and the potential energy surface minima were indicated by analysis of vibrational frequencies. The gasphase basicity and proton affinity were calculated via a protonation reaction, using Gibbs energies and enthalpies, respectively. 30 Cardozo et al. 1627 Vol. 20, No. 9, 2009 Results and Discussion Mycosporine-like amino acids with one acidic function were previously analysed by positive mode ESI sequential mass spectrometry (at high-resolution and accurate-mass). The loss of a methyl radical by the homolytic cleavage of the O-C bond was observed to be the preferred fragmentation pathway. As expected, analysis in negative ion mode Conclusions These results indicate that the presence of a second carboxylic acid function significantly reduces the intensity of the observed product ions from the radical methyl cleavage in positive mode MS/MS. As expected, in the negative ion mode, the radical fragmentation pathway does not occur. Taken together, these results confirm the importance of careful selection of the product ions used for analytical protocols for the analysis of crude extracts containing MAAs where the presence of the second acid function may change the fragmentation behavior and the classical analysis of loss of methyl radical may lead to the wrong conclusions during screening for MAAs

Projeto ExPOSE: criação de protocolos para avaliação da exposição ocupacional ao microbiota em ambientes clínicos

FCT - 02/SAICT/2016 – Project nº 23222Nas últimas décadas, tem sido enfatizada a importância dos bioaerossóis em ambientes interiores, pelos efeitos adversos que causam na saúde humana e consequente impacto na saúde pública. Os hospitais e restantes unidades de saúde, pelas caraterísticas inerentes aos mesmos podem potenciar a contaminação microbiana, pelo que requerem uma atenção e intervenção especial para proteger, não só os pacientes mas também os profissionais de saúde, das infeções associadas aos cuidados de saúde e das doenças profissionais. O projeto ExPOSE tem como objetivo avaliar a exposição dos trabalhadores ao microbiota em unidades de cuidados de saúde e consequente elaboração de orientações para a redução dessa exposição.info:eu-repo/semantics/publishedVersio

Synthesis of 7-Chloroquinoline Derivatives Using Mixed Lithium-Magnesium Reagents

We have prepared a library of functionalized quinolines through the magnesiation of 7-chloroquinolines under mild conditions, employing both batch and continuous flow conditions. The preparation involved the generation of mixed lithium-magnesium intermediates, which were reacted with different electrophiles. Mixed lithium-zinc reagents allowed the synthesis of halogenated and arylated derivatives. Some of the synthesized 4-carbinol quinolines have shown interesting antiproliferative properties, their hydroxyl group being a suitable amino group bioisostere. We also report a two-step approach for optically active derivatives

Systematic UPLC-ESI-MS/MS study on the occurrence of staurosporine and derivatives in associated marine microorganisms from Eudistoma vannamei

Former bioactivity-guided analysis of the marine invertebrate Eudistoma vannamei led to the isolation of staurosporine derivatives, which revealed strong cytotoxic activity against several human cancer cell lines. The occurrence of such alkaloids in E. vannamei may be correlated to the presence of associated biota, such as Streptomyces bacteria. In agreement to this hypothesis, marine microorganisms associated with E. vannamei were recovered and cultured, leading to a total of 84 isolated bacterial strains. Gas phase fragmentation reactions of staurosporine and derivatives were systematically studied and the analyzed results further supported by computational chemistry studies. The resulting fragment patterns were used to search for the presence of different derivatives in extracts of isolated microorganisms, thereby using LC-MS/MS analysis in MRM mode. These results evidenced that one isolated Streptomyces sp. was able to generate staurosporine, while none of the hydroxy-7-oxo derivatives were detected. Finally, significant cytotoxic activity against human cancer lines was observed for one of the extracts

The use of computational chemistry in the studies of chemical processes involved in electrospray ionization

Nas últimas décadas, o desenvolvimento das técnicas de ionização à pressão atmosférica impulsionou a espectrometria de massas, na caracterização e elucidação estrutural de compostos de grande massa molecular. O surgimento dessas técnicas foi o responsável pela amplitude nas aplicações e estudos de espectrometria de massas, sendo a ionização por electrospray a mais versátil dentre essas fontes de ionização. O caráter eletrolítico da fonte de ionização por electrospray permite-se obter íons provenientes de três processos químicos: i) ácido-base; ii) redox e iii) complexação. A extensão com que cada um desses processos ocorrerá dependerá de fatores relacionados à operação da fonte de ionização e grandezas termoquímicas do analito. O notável progresso em técnicas experimentais, processamento de dados e integração entre as mais diversas áreas de aplicação da química, tem estimulado e beneficiado a aplicação da química teórica em estudos de reações em fase gasosa. A aplicação da química computacional fornece uma compreensão quantitativa das variações estruturais e energéticas dos possíveis íons formados durante a ionização da amostra, permitindo também a compreensão das possíveis vias de dissociação. É neste sentido, que o sinergismo entre a aplicação de conceitos derivados da química quântica pode auxiliar nas análises de espectrometria de massas. O objetivo desta tese foi o de se aplicar os modelos fundamentados na mecânica quântica para obtenção de grandezas termoquímicas relacionadas aos fenômenos que ocorrem durante as análises de espectrometria de massas por electrospray. Inicialmente, a comparação entre métodos ab initio, modelos compostos e aqueles embasados na teoria do funcional de densidade foram empregados nos cálculos das grandezas termoquímicas para a -butirolactona e 2-pirrolidinona, com a finalidade de se obter parâmetros termoquímicos de alta qualidade. Os modelos compostos G2, G2(MP2), CBS-Q, CBS-QB3 e os métodos B3LYP, B3P86, B98, PW91PW91 e MP2 foram testados. Os valores obtidos para a entalpia de formação, afinidade protônica e basicidade em fase gasosa para essas duas moléculas foram comparados aos dados experimentais disponíveis na literatura. Os melhores resultados para os valores de entalpia de formação foram obtidos ao se empregar o modelo B3LYP/6-31+G(d,p). A afinidade protônica e basicidade em fase gasosa foram mais bem descritas por B3LYP e G2(MP2). Posteriormente, foram estudadas a 1,4-benzoquinona, 1,4-naftoquinona, bem como seus derivados (2-acetilamina-1,4-naftoquinona; 2-propionilamina-1,4-naftoquinona; 2-butirilamina-1,4-naftoquinona, 2-benzoilamina-1,4-naftoquinona, 2-succinilamina-1,4-naftoquinona e lapachol). A escolha do modelo teórico empregado foi realizada por se comparar as geometrias, afinidade protônica, basicidade em fase gasosa, energia de ionização e afinidade eletrônica obtidos para a 1,4-benzoquinona com aqueles disponíveis na literatura. O modelo B3LYP/6-31+G(d,p) foi o mais exato com relação as grandezas termoquímicas supracitadas, assim, este modelo foi empregado no cálculo dessas mesmas grandezas para a 1,4-naftoquinona e seus derivados. A influência do substituinte na estrutura eletrônica dessas moléculas protonadas, desprotonadas, oxidadas, reduzidas e cationizadas foi estudada utilizando-se análises energéticas, geométricas, eletrônicas e topológicas. O desenvolvimento desses estudos compreendeu as análises das grandezas termoquímicas e análises da densidade eletrônica pelos métodos NBO (Natural Bond Orbital), NSA (Natural Steric Analysis), NRT (Natural Resonance Theory) e AIM (Atoms in molecules). A ionização por electrospray e a dissociação induzida por colisão foram realizadas para os derivados da 1,4-naftoquinona, sendo analisados suas moléculas protonadas, desprotonadas, reduzidas, oxidadas e cationizadas com Na+. As vias mecanísticas de dissociação foram embasadas nas análises da superfície de energia obtidas pelo cálculo das energias de Gibbs e entalpias.In recent decades, the development of atmospheric ionization techniques improved mass spectrometry, principally for characterization and structural elucidation of high-molecular weight compounds. The development of spray ionization was responsible for the spread of applications and studies of mass spectrometry, where the electrospray ionization is the most versatile among the ionization sources. The electrolytic character of electrospray source allows obtaining ions by three different chemical processes: i) acid-base; ii) redox and, iii) metal complexation. These processes will occur through several factors which can be related to the ionization source and thermochemical parameters of analyte. The notable progress of experimental analyses, computational data and the integration between several areas of chemical application have stimulated the use of theoretical chemistry at gas-phase studies. Computational chemistry can furnish a quantitative understanding of the structure and energy of possible ions during the ionization process. For this reason, the synergism between the concepts from quantum chemistry and gas-phase chemistry can help mass spectrometry analysis. The main purpose of this thesis was the application of several quantum mechanical models to obtain thermochemical parameters which can be related to mass spectrometry phenomena. Firstly, the comparison between ab initio, composite model and DFT methods were employed to obtain the thermochemical parameters to -butyrolactone e 2-pyrrolidinona, in order to obtain high performance of thermochemical parameters. The composite G2, G2(MP2), CBS-Q and, the B3LYP, B3P86, B98, PW91PW91 and MP2 methods were tested. The calculated values were compared to experimental values reported in the literature. The best results for enthalpies of formation were obtained when B3LYP/6-31+G(d,p) model was employed. The proton affinity and gas-phase basicity were better described by using of B3LYP and G2(MP2). Secondly, the studies with quinones were performed, where the 1,4-benzoquinone, 1,4-naphthoquinone and its derivatives (2-acylamino-1,4-naphthoquinone; 2-propyonilamino-1,4-naphthoquinone; 2-butyrilamino-1,4-naphthoquinone; 2-benzoylamino-1,4-naphthoquinone; 2-succynilamino-1,4-naphtoquinone and, lapachol) were studied. A search for a theoretical model was made to compare the geometries, proton affinity, gas-phase basicity, ionization energy and electron affinity to 1,4-benzoquinone with those reported in the literature. The most accurate results were obtained by using of B3LYP/6-31+G(d,p). Thus, this model was applied in all studies with 1,4-naphthoquinone derivatives. The influence of substituent groups on electronic structure of protonated, deprotonated, reduced, oxidized and cationized molecules were studied by energetic, geometrics, electronics and topological analyses. The development of these studies and the determination of the thermochemical parameters and wave function analysis was achieved by means of Natural Bond Orbitals, Natural Steric Analysis, Natural Resonance Theory and Atoms in Molecules The electrospray ionization and gas-phase collision-induced dissociation were made for the 1,4-naphtoquinone derivatives by analyzing their protonated, deprotonated species, the radicalar and sodiated ones. The main fragmentation pathways were elucidated on the basis of the energy surface by using Gibbs energies and enthalpies

Evaluation of the enthalpy of formation, proton affinity, and gas-phase basicity of gamma-butyrolactone and 2-pyrrolidinone by isodesmic reactions

The knowledge of thermochemical parameters such as the enthalpy of formation, gas-phase basicity, and proton affinity may be the key to understanding molecular reactivity. The obtention of these thermochemical parameters by theoretical chemical models may be advantageous when experimental measurements are difficult to accomplish. The development of ab initio composite models represents a major advance in the obtention of these thermochemical parameters,. but these methods do not always lead to accurate values. Aiming at achieving a comparison between the ab initio models and the hybrid models based on the density functional theory (DFT), we have studied gamma-butyrolactone and 2-pyrrolidinone with a goal of obtaining high-quality thermochemical parameters using the composite chemical models G2, G2MP2, MP2, G3, CBS-Q, CBS-4, and CBS-QB3; the DFT methods B3LYP, B3P86, PW91PW91, mPW1PW, and B98; and the basis sets 6-31G(d), 6-31+G(d), 6-31G(d,p), 6-31+G(d,p), 6-31++G(d,p), 6-311G(d), 6-311+G(d), 6-311G(d,p), 6-311+G(d,p), 6-311++G(d,p), aug-cc-pVDZ, and aug-cc-pVTZ. Values obtained for the enthalpies of formation, proton affinity, and gas-phase basicity of the two target molecules were compared to the experimental data reported in the literature. The best results were achieved with the use of DFT models, and the B3LYP method led to the most accurate data