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Producción Científica, DOPAC, a relevant scaffold in dopamine metabolism, was probed in the gas phase and interrogated by high-resolution rotational spectroscopy. Herein, three distinct conformers were isolated in a supersonic jet and identified for the first time through an examination of the trend of the rotational constants and the dipole moment selection rules. Additionally, we examined the plausible relaxation pathways of the low-energy conformers of DOPAC, which helped us to claim the indirect detection of two additional conformers, providing conclusive experimental evidence of the flexible nature of this biomolecule. The current investigation sheds some light on the differences between jet-cooled rotational experiments and matrix-isolation infrared spectroscopy., Ministerio de Ciencia e Innovación (CTQ2016-76393-P and PID2019- 111396 GB-I00), Junta de Castilla y León (VA077U16 and VA244P20), European Research Council under the European Union’s Seventh Framework Programme (FP/2007- 2013)/ERC-2013-SyG, Grant Agreement n. 610256 NANOCOSMOS

Producción Científica, The unbiased, naked structures of tartaric acid, one of the most important organic compounds existing in nature and a candidate to be present in the interstellar medium, has been revealed in this work for the first time. Solid samples of its naturally occurring (R,R) enantiomer have been vaporized by laser ablation, expanded in a supersonic jet, and characterized by Fourier transform microwave spectroscopy. In the isolation conditions of the jet, we have discovered up to five different structures stabilized by intramolecular hydrogen-bond networks dominated by O−H⋅⋅⋅O=C and O−H⋅⋅⋅O motifs extended along the entire molecule. These five forms, two with an extended (trans) disposition of the carbon chain and three with a bent (gauche) disposition, can serve as a basis to represent the shape of tartaric acid. This work also reports the first set of spectroscopy data that can be used to detect tartaric acid in the interstellar medium., Ministerio de Ciencia e Innovación (CTQ2016- 76393-P y PID2019-111396GB-I00), Junta de Castilla y León (Subvenciones VA077U16 y VA244P20)

Dissertação de Mestrado em Física apresentada à Faculdade de Ciências e Tecnologia Máquinas moleculares e as suas aplicações são uma área de investigação que se tem desenvolvido bastante tendo mesmo a Academia Real Sueca de Ciências laureado os cientistas Jean-Pierre Sauvage, Sir James Fraser Stoddart e Bernard L. Feringa com o prémio Nobel de Química em 2016 "pelo design e síntese das máquinas moleculares". Muitas classes de moléculas podem ser usadas para construir estas máquinas minúsculas, como por exemplo a classe das iminas. As iminas, que normalmente são relativamente fáceis de sintetizar, podem funcionar como motores moleculares de dois ou quatro passos. Esta tese foca-se no estudo conformacional de uma imina de canforaquinona e dos complexos que esta forma com moléculas de água, usando espectroscopia rotacional. Esta imina tem dois isómeros (E e Z) e pode transitar entre os dois quando excitada com luz com um comprimento de onda bem determinado, de forma reversível, tornando-se assim um interruptor molecular. Uma caracteristica interessante desta molécula é que um isómero (Z) é mais estável na fase gasosa, enquanto o outro (E) é mais estável em solução. A espectroscopia rotacional é uma técnica experimental em que radiação de microondas é usada para investigar transições entre os níveis de energia rotacionais de uma molécula. As frequências destas transições podem ser relacionadas com a estrutura molecular através dos momentos principais de inércia da molécula. Assim, medidas do espectro rotacional de isotopólogos (muitas vezes em abundância natural) permitem-nos calcular as posições dos átomos na molécula. A espectroscopia rotacional é pois uma ferramenta incrível para o estudo da estrutura de moléculas isoladas. Os espectros de alta resolução analisados nesta tese foram obtidos com o espectrómetro de microondas, COMPACT, em Hamburgo. Para analisar um espectro rotacional é necessário ter uma previsão inicial, aproximada, para várias propriedades da molécula. Esta estimativa foi obtida com cálculos de química quântica feitos usando o programa ORCA. Foi utilizada a teoria dos funcionais da densidade com o funcional B3LYP, uma correção de dispersão entre pares de átomos com o esquema de amortecimento de Becke-Johnson (D3BJ), e a base def2-TZVP para obter a energia e geometria das moléculas bem como o seu dipolo elétrico e as suas constantes de acoplamento do quadrupolo nuclear. A análise dos espectros rotacionais permitiu identificar inequivocamente as espécies predominantes contidas no jato molecular. Para a molécula isolada, foram observadas as duas conformações sendo o isómero Z muito mais prevalente. No complexo com uma molécula de água, os dois isómeros são visíveis. No complexo com duas moléculas de água, só conseguimos observar o complexo com o isómero E. Os valores experimentais finais obtidos por refinamento do modelo para melhor ajuste aos dados experimentais diferem da previsão inicial em cerca de 1 a 2% para as constantes rotacionais e 10 a 20% para as constantes de acoplamento do quadrupolo nuclear. O uso de cálculos de teoria de perturbação de simetria adaptada (SAPT) e de análises de interações não-covalentes permitiram-nos perceber e visualizar as interações não-covalentes intramoleculares e intermoleculares e como estas afetam a estabilidade relativa dos isómeros. Para a molécula isolada, a maior estabilidade do isómero Z deve-se à presença de duas ligações de hidrogénio intramoleculares que estão ausentes no outro isómero. Nos complexo com uma molécula de água, a interação primária, que liga os monómeros, em ambos os isómeros é a mesma, uma ligação de hidrogénio entre o átomo azoto da imina e um átomo de hidrogénio da água. Assim, a estabilidade relativa observada surge como consequência de interações secundárias. Com base nesta investigação ficou claro que a espectroscopia rotacional, em combinação com cálculos de química quântica, é uma ferramenta poderosa para o estudo e elucidação da estrutura e interações de moléculas e complexos fracamente ligados. Molecular machines and their applications are an area of research which has greatly developed, with the Royal Swedish Academy of Science awarding the 2016 Nobel prize in Chemistry to Jean-Pierre Sauvage, Sir James Fraser Stoddart and Bernand L. Feringa "for the design and synthesis of molecular machines". Many classes of molecules, like for example imines, can be used to create these small machines. Imines, which are generally relatively easy to synthesize, can function as two or four step molecular motors. This thesis focuses on a conformational study of a camphorquinone imine and the complexes it forms with water molecules using rotational spectroscopy. This imine has two isomers (E and Z) and can transition between the two using when excited using light with a well defined wavelength, in a reversible manner, and as such can work as a molecular switch. An interesting property of this molecule is that while one isomer (Z) is the more stable in the gas phase, the other (E) is the more stable in solution.Rotational spectroscopy is a experimental technique where microwave radiation is used to investigate transitions between the rotational energy levels of a molecule. The transition frequencies can be related to the molecular structure through the principal moments of inertia. As such, measurements of the rotational spectra of isotopologues (many times done at natural abundance) allow us to calculate the positions of atoms in the molecule. Rotational spectroscopy is thus an incredible tool for the study of the structure of isolated molecules. The high resolution spectra used in this dissertation were obtained using the broadband microwave spectrometer, COMPACT, in Hamburg. To analyse a rotational spectrum, it is necessary to have an approximate initial guess to multiple molecular properties. This estimate was obtained using quantum chemistry calculations performed using ORCA. We used density functional theory with the B3LYP functional, an atom-pairwise dispersion correction with the Becke-Johnson damping scheme (D3BJ), and the def2-TZVP basis set to obtain the energy and geometry of the molecules as well as their electric dipole moment and nuclear quadrupole coupling constants. The analysis of the spectra allowed us to unequivocally identify the species present in the molecular jet. For the isolated molecules, we observed both conformations although the Z isomer was much more prevalent. For the complexes with one water molecule, both isomers were also visible. For the complexes with two water molecules, only the E isomer form could be observed. The experimental values obtained by refining our models to best fit the experimental data differ from our initial predictions by about 1 to 2% for the rotational constants and 10 to 20% for the nuclear quadrupole coupling constants.The use of symmetry adapted perturbation theory (SAPT) calculations and non covalent interaction analysis (NCI) allowed us to understand and visualise the intramolecular and intermolecular non-covalent interactions, and how these affect the relative stability of the isomers. For the isolated molecule, the greater stability of the Z isomer is due to the presence two intramolecular hydrogen bonds which are absent in the other isomer. In the complexes with one water molecule, the primary interaction, which binds the monomers, is the same, a hydrogen bond between the nitrogen atom of the imine and one of the hydrogen atoms of the water. As such, the observed relative stability appears as a consequence of secondary interactions. From this investigation it became clear that rotational spectroscopy, in combination with quantum chemistry calculations, is a powerful tool for the study and elucidation of structure and interactions of molecules and weakly bound complexes.

Producción Científica, The rotational spectrum (4–40 GHz and 50–330 GHz) has been measured and analyzed for trifluoroacetaldehyde, also known as fluoral (CF3CHO), which is one of the degradation products of the fluorinated contaminants emitted into the atmosphere. The complexity of the spectroscopic analysis of this molecule arises from the strong coupling between the internal rotation motion of CF3 group and the overall rotation of the molecule. The value obtained for its coupling constant (ρ = 0.91723481(49)) is comparable to the corresponding value of methanol (CH3OH, ρ = 0.81), which is known for its complex spectrum. A total of 12,322 transitions of the ground, the first and second excited torsional states (ΔE1υt = 62.0183(13)cm−1; ΔE2υt = 120.3315(13)cm−1) with J ≤ 50 were included in the analysis that was performed employing the rho-axis-method (RAM), and the RAM36 code. A fit within experimental error (root mean square deviation equals to 35 kHz) has been achieved for this dataset using 47 parameters of the RAM torsion-rotation Hamiltonian. In the course of the analysis, it became evident that for such high ρ value, as it is determined for fluoral, a larger than usual torsional basis set at the first diagonalization step of the two-step diagonalization procedure is required for achieving a fit within experimental error., National French Programme “ANR Labex CaPPA” through the PIA (contract ANR-11-LABX-0005-01), Ministry of Science and Technology of Taiwan (grants MOST 104-2113-M-009-020 and MOST 105-2811-M-009-026)

La D-penicilamina es un fármaco trifuncional con el que es posible tratar una gran variedad de enfermedades. En el presente trabajo se aborda, por primera vez, el estudio de su estructura tridimensional con el fin de poder entender en mayor manera cómo ejerce su potencial actividad biológica. Mediante el uso de una técnica de ablación láser, se ha transferido la muestra sólida de penicilamina a fase gas, para después ser expandida supersónicamente e interrogada con una radiación en el rango de frecuencias de microondas, con la técnica conocida como Laser Ablation Chirped Pulse Fourier Transform Microwave (LA-CP-FTMW) de espectroscopia de rotación, desarrollada en el Grupo de Espectroscopia Molecular (GEM) de la Universidad de Valladolid. El espectro de rotación de la D-penicilamina ha sido obtenido experimentalmente, siendo capaces de identificar dos confórmeros dominantes que se corresponden con las dos estructuras predichas más estables de la molécula. Paralelamente, se han empleado métodos computacionales (mecánica molecular y cálculos mecanocuánticos), con el fin de buscar las estructuras más relevantes, o más estables, y así tener una predicción de los parámetros rotacionales que sirvan de guía en la asignación del espectro experimental. Finalmente, se ha llevado a cabo un análisis de las fuerzas intermoleculares de los dos confórmeros para poder discutir si existe alguna correlación entre la estructura y el papel biológico que ejerce la penicilamina., D-penicillamine is a drug widely used to treat many diseases. In the present work, we characterize the three-dimensional structure of penicillamine as a first approach to shed light on its biological activity. Using a laser ablation source, we have transferred solid D-penicillamine to the gas phase by Laser Ablation (LA) and probed it employing Chirped Pulsed Fourier Transform Microwave (CP-FTWM) spectroscopy in the isolated conditions of a supersonic jet. This technique has been designed and developed by Grupo de Espectroscopia Molecular (GEM) in the University of Valladolid. On the one hand, we use computational methods (both molecular mechanics and quantum chemical calculations), to search for the most relevant structures. This allows us to obtain the most stable structures and make a prediction of the rotational spectra in order to proceed with their assignment. At the same time, the experimental rotational spectrum of D-penicillamine is obtained, and two conformers are found which correspond to the predicted most stable conformers. Finally, a characterization of the intermolecular forces is carried out to discuss any correlation with the biological role of penicillamine., Departamento de Química Física y Química Inorgánica, Grado en Química

Chirality is determinant for sphingosine biofunctions and pharmacological activity, yet the reasons for the biological chiral selection are not well understood. Here, we characterized the intra- and intermolecular interactions at the headgroup of the cytotoxic anhydrophytosphingosine jaspine B, revealing chirality-dependent correlations between the puckering of the ring core and the formation of amino-alcohol hydrogen bond networks, both in the monomer and the monohydrate. Following the specific synthesis of a shortened 3-carbon side-chain molecule, denoted jaspine B3, six different isomers were observed in a jet expansion using broadband (chirped-pulsed) rotational spectroscopy. Additionally, a single isomer of the jaspine B3 monohydrate was observed, revealing the insertion of water in between the hydroxy and amino groups and the formation of a network of O-H···N-H···Oring hydrogen bonds. The specific jaspine B3 stereochemistry thus creates a double-faced molecule where the exposed lone-pair electrons may easily catalyze the formation of intermolecular aggregates and determine the sphingosine biological properties., Funding support from the Spanish MICINN-FEDER (grant PGC2018-098561-B-C22) is gratefully acknowledged. M.J. and R.T.S. are thankful for predoctoral contracts from the MICINN and UVa, respectively.

Dissertação de mestrado, Inovação Quimica e Regulamentação, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015 Sulfa-drug derivatives, such as Benzenesulfonamide (BSA), para-Toluenesulfonamide (p-TSA), ortho-Toluenesulfonamide (o-TSA), and Sulfanilamide (SAM), are widely used in the chemical industry. However, these polar organic compounds constitute emerging environmental concerns. Unfortunately, there is lack of eco-toxicological data for these substances but some insight can be obtained by analyzing the molecular structure and conformational properties of the compounds which can aid with the understanding of their biological mechanisms. Rotational spectroscopy coupled with high level theoretical calculations can supply these data. In this dissertation, the structural information and conformational properties of the sulfa-drug derivatives were obtained by a combined study of rotational spectroscopy in free jet expansions and quantum chemical calculations (B3LYP and MP2 at 6-311++G** level of theory). The effect of the added substituents (ortho/para-CH3 and para-NH2), in terms of structural parameters, were investigated as well since BSA is the molecular backbone of o-TSA, p-TSA, and SAM. Results showed that the four sulfa-drug derivatives favour the eclipsed conformation of the –NH2 and –SO2 groups but rationalization behind this preference varies among the compounds. Conversely, addition of –CH3 and –NH2 in the para position has no significant effects on the structural parameters of BSA but addition of ortho-CH3 brought some dramatic changes in the bond angles. European Commission: scholarship funded within the Erasmus+ KA1 Programme, ref. 2013-0241 – Erasmus Mundus Joint Master Degree in Chemical Innovation and Regulation