Molecular aggregation of thiols and alcohols: study of non-covalent interactions by microwave spectroscopy

El estudio y comprensión de las interacciones no covalentes a nivel molecular es un campo que está en continuo desarrollo y cobra vital importancia para determinar el comportamiento estructural de muchas moléculas de interés químico, tecnológico o biológico. En esta tésis doctoral se han analizado las interacciones intermoleculares implicadas en la formación de agregados moleculares neutros, tanto dímeros como productos de microsolvatación, en fase gas. Los complejos intermoleculares se han generado mediante expansiones supersónicas pulsadas, caracterizándose posteriormente mediante espectroscopía de rotación. Este trabajo ha utilizado dos técnicas espectroscópicas, incluyendo un espectrómetro de microondas con transformada de Fourier (FTMW) de tipo Balle-Flygare en el rango de frecuencias 8-20 GHz, y un espectrómetro de transformada de Fourier de banda ancha con excitación multifrecuencia (CP-FTMW) cubriendo el rango espectral de 2-8 GHz. Los complejos intermoleculares estudiados han incluido moléculas con grupos alcohol y/o tiol, con objeto de analizar las diferencias entre las interacciones intermoleculares que implican átomos de oxígeno o azufre, en especial el enlace de hidrógeno. Se han estudiado moléculas incluyendo tanto sistemas cíclicos alifáticos (ciclohexanol, ciclohexanotiol) como aromáticos (furfuril alcohol, furfuril mercaptano, tienil alcohol, tienil mercaptano). Los enlaces de hidrógeno analizados han comprendido especialmente interacciones de tipo O-H···O, O-H···S y S-H···S. La formación de los complejos intermoleculares ha revelado en algunos de ellos una gran variedad conformacional, como la observación de seis isómeros del dímero de ciclohexanol. En el caso de los monohidratos se han observado en algunos casos desdoblamientos asociados a movimientos internos de gran amplitud, como la rotación de la molécula de agua en los monohidratos de ciclohexanol y tienil mercaptano. En los casos de moléculas quirales la dimerización ha permitido observar la estabilidad relativa de los diastereoisómeros homo o heteroquirales. El estudio experimental se ha completado con diferentes cálculos teóricos de orbitales moleculares, en especial teoría del funcional de la densidad, a fin de caracterizar las interacciones estructuralmente, energéticamente y mediante análisis topológico de la densidad electrónica. El conjunto de datos experimentales y teóricos permite aumentar la información existente sobre enlaces de hidrógeno con átomos de azufre, generalmente poco estudiados, y su comparación con los análogos oxigenados.The study and understanding of non-covalent interactions at molecular level is a field in continuous development and essential to determine the structural behavior of many molecules of chemical, technological or biological interest. In this PhD thesis, the intermolecular interactions involved in the formation of neutral molecular aggregates, both dimers and microsolvation products, have been analyzed in the gas phase. The intermolecular complexes were generated by pulsed supersonic expansions, and later characterized by rotational spectroscopy. This work has used two spectroscopic techniques, including a Balle-Flygare Fourier-Transform Microwave (FTMW) spectrometer in the 8-20 GHz frequency range, and a broadband Chirped-Pulse Fourier Transform Microwave (CP-FTMW) spectrometer covering the 2-8GHz spectral range. The intermolecular complexes studied have included molecules with alcohol and / or thiol groups, in order to analyze the differences between the intermolecular interactions involving oxygen or sulfur atoms, especially hydrogen bonds. Molecules that comprise both aliphatic (cyclohexanol) and aromatic (furfuryl alcohol, furfuryl mercaptan, thenyl alcohol, thenyl mercaptan) ring systems have been studied. The analyzed hydrogen bonds included especially O-H···O, O-H···S and S-H···S interactions. The formation of intermolecular complexes has revealed a great conformational diversity in some of them, such as the observation of six isomers of the cyclohexanol dimer. With regard to the monohydrates, tunnelling splittings associated with internal large amplitude motions have been observed in some cases, such as the rotation of the water molecule in the monohydrates of cyclohexanol, thenyl alcohol and thenyl mercaptan. In the case of chiral molecules, dimerization has made it possible to observe the relative stability of homo- or heterochiral diastereoisomers. The experimental study has been supported by different theoretical molecular orbital calculations, in particular Density Functional Theory (DFT) calculations, in order to characterize the interactions structurally, energetically and by a topological analysis of electron density. The set of experimental and theoretical data will advance the existing information on hydrogen bonds involving sulfur atoms, generally scarcely studied, and their comparison with the oxygenated analogues.Departamento de Química Física y Química InorgánicaDoctorado en Físic

HYDROGEN BONDING IN THE MONOHYDRATES AND HOMODIMERS OF CYCLOHEXYLAMINE AND CYCLOHEXANETHIOL

\begin{wrapfigure}{r}{0pt} \includegraphics[scale=0.3]{Image1.eps} \end{wrapfigure} Following previous investigation of the monohydrate\footnote{M. Juanes, W. Li, L. Spada, L. Evangelisti, A. Lesarri, W. Caminati, \textit{Phys.Chem.Chem.Phys.}, \textbf{2019}, 21, 3676.} and homodimer of cyclohexanol\footnote{M. Juanes, I. Le\'{o}n, R. Pinacho, J. E. Rubio, W. Li, L. Evangelisti, W. Caminati, A. Lesarri, Comm. WK09, 73rd ISMS (Urbana-Champaign), \textbf{2018}.}, we have examined the non-covalent interactions in the saturated six-membered rings of cyclohexylamine (CA) and cyclohexanethiol (CT), using chirped-pulsed and cavity Fourier-transform microwave spectroscopy (2-18 GHz). Water behaves as proton donor to both CA and CT, generating two isomers in CT $\cdot$$\cdot$$\cdot$ H$_{2}$O (equatorial-gauche and equatorial-trans) and a single isomer in CA $\cdot$$\cdot$$\cdot$ H$_{2}$O (equatorial gauche-trans). Torsional splittings were observed for CT $\cdot$$\cdot$$\cdot$ H$_{2}$O, while nuclear quadrupole coupling effects were resolved for CA $\cdot$$\cdot$$\cdot$ H$_{2}$O. The predicted hydrogen bond distances in the hydrated amine and thiol are enlarged with respect to the alcohol (r$_{O H}$$_{\cdot}$$_{\cdot}$$_{\cdot}$$_{S}$)=2.47{\AA} and (r$_{O-H}$$_{\cdot}$$_{\cdot}$$_{\cdot}$$_{N}$)=1.91{\AA} vs (r$_{O-H}$$_{\cdot}$$_{\cdot}$$_{\cdot}$$_{O}$)=1.88{\AA}). Work on the CA$_{2}$ and CT$_{2}$ dimers will also be reported. In these dimers the hydrogen bonds are characterized by r$_{O-H}$$_{\cdot}$$_{\cdot}$$_{\cdot}$$_{O}$=1.88{\AA} and r$_{O-H}$$_{\cdot}$$_{\cdot}$$_{\cdot}$$_{N}$=1.91 \AA. Rotational data and supporting ab initio calculations will be presented for the investigated species

SULFUR HYDROGEN BONDING IN THE OLIGOMERS OF AROMATIC THIOLS

\begin{wrapfigure}{l}{0pt} \includegraphics[scale=0.3]{Image2.eps} \end{wrapfigure} Following previous experiments on sulfur hydrogen bonding\footnote{M. Juanes, A. Lesarri, R. Pinacho, E. Charro, J. E. Rubio, L. Enríquez, M. Jaraíz, \textit{Chem. Eur. J.}, \textbf{2018}, 24, 6564} we have observed several oligomers of the aromatic thiols thiophenol, phenylmethanethiol and 2-phenylethanethiol in a jet-cooled expansion using broadband (chirped-pulsed) microwave spectroscopy (2-8 GHz).The homodimers of the three aromatic thiols are primarily stabilized by S-H $\cdot$$\cdot$$\cdot$ S hydrogen bonds and other weak interactions. The phenylmethanethiol and 2-phenylethanethiol dimers exhibit additional combinations of S-H $\cdot$$\cdot$$\cdot$ $\pi$, C-H $\cdot$$\cdot$$\cdot$ $\pi$ or C-H $\cdot$$\cdot$$\cdot$ S interactions, while the two phenyl rings in the thiophenol dimer are stacked, displaying a $\pi$-$\pi$ interaction. A single symmetric-top isomer of the thiophenol trimer has been observed, characterized by a C$_{3}$ symmetry topologically equivalent to that observed in the phenol\footnote{N. A. Seifert, A. L. Steber, J. L. Neill, C. Pérez, D. P. Zaleski, B. H. Pate, A. Lesarri, \textit{Phys. Chem. Chem. Phys.}, \textbf{2013}, 15, 11468} and aniline\footnote{C. Pérez, I. León, A. Lesarri, B. H. Pate, R. Martínez, Judith Millán, J. A. Fernández, \textit{Angew. Chem. Int. Ed.}, \textbf{2018}, 57, 15112} trimers. The trimer structure combines S-H $\cdot$$\cdot$$\cdot$ S hydrogen bonds and C-H $\cdot$$\cdot$$\cdot$ $\pi$ interactions. Accurate rotational parameters and supporting ab initio and DFT calculations will be reported at the symposium

DIMERIZATION AND MICROSOLVATION OF 2- AND 3-THIOPHENEETHANOL

\begin{wrapfigure}{l}{0pt} \includegraphics[scale=0.55]{Image4.eps} \centering \end{wrapfigure} We are using rotational spectroscopy to examine sulfur hydrogen bonding in a series of thiophene and furan mercapto derivatives\footnote{M. Juanes, A. Lesarri, R. Pinacho, E. Charro, J. E. Rubio, L. Enríquez, M. Jaraíz, \textit{Chem. Eur. J.}, \textbf{2018}, 24, 6564}, in order to compare their aggregation properties with those of the equivalent alcohols. Here we report on the dimers and monohydrates of 2-thiopheneethanol (2TE) and 3-thiopheneethanol (3TE), isolated in a jet-cooled expansion. Two isomers of (2TE)$_{2}$, three isomers of (3TE)$_{2}$ and the two monohydrates 2TE···H$_{2}$O and 3TE···H$_{2}$O were observed using chirped-pulsed and cavity Fourier transform microwave spectroscopy (2-18 GHz). The dimers are primary bound in all cases by the stronger O-H···O interaction (r$_{O-H}$$_{\cdot}$$_{\cdot}$$_{\cdot}$$_{O}$ ca. 1.88 Å) originated by the alcohol groups. In the monohydrates water behaves as a proton acceptor, and the spectrum shows evidence of torsional tunneling. Rotational parameters and supporting ab initio calculations will be reported

THE CYCLOHEXANOL DIMER AND THE MONOHYDRATE: INTERNAL ROTATION AND CONVERSION FROM TRANSIENT TO PERMANENT CHIRALITY

\begin{wrapfigure}{l}{0pt} \includegraphics[scale=0.153]{ch-abstract.eps} \end{wrapfigure} The conformational preferences, molecular structure and intramolecular dynamics of cyclohexanol (CHOL), the cyclohexanol dimer (CHOL$_{2}$) and cyclohexanol-water (CHOL···H$_{2}$O) have been analyzed using rotational spectroscopy in a supersonic jet expansion. The monomer conformation is controlled by ring inversion (equatorial/axial) and alcohol internal rotation (gauche+/gauche- or trans). Both equatorial trans (rigid) and equatorial gauche (tunneling) isomers were observed, but axial cyclohexanol went undetected. The monohydrate CHOL···H$_{2}$O exhibits a single hydrogen bonded equatorial gauche conformation, with tunneling splittings revealing a concerted motion of the hydroxyl and water molecules. The formation of the dimer CHOL$_{2}$ stabilizes the transient chirality of the gauche+/gauche- monomer conformations, as different chiral combinations donor-acceptor result in permanent chirality. This molecular dimer represent a larger level of complexity compared with previous studies \footnote{M. S. Snow, B. J. Howard, L. Evangelisti, W. Caminati, \textit{J. Phys. Chem. A} \textbf{2011}, 115, 47.}\footnote{A. K. King, B. J. Howard, \textit{Chem. Phys. Lett.} \textbf{2001}, 348, 343.}, as 36 different donor-acceptor combinations are now possible and the relative orientation of the two rings generates multiple conformations. Finally, six different isomers were observed for the dimer. Accurate rotational parameters for the observed conformations and supporting ab initio and DFT calculations will be reported

SULFUR HYDROGEN BONDING: A COMPARISON OF THE DIMERS AND MONOHYDRATES OF THENYL AND FURFURYL ALCOHOLS AND MERCAPTANS

\begin{wrapfigure}{r}{0pt} \includegraphics[scale=0.18]{dimer_comb_2_v2.eps} \end{wrapfigure} The dimers of thenyl alcohol (TA$_{2}$) and furfuryl alcohol (FA$_{2}$), and the monohydrates of both alcohols (TA$\cdot$$\cdot$$\cdot$H$_{2}$O, FA$\cdot$$\cdot$$\cdot$H$_{2}$O) and their corresponding mercaptans (TM$\cdot$$\cdot$$\cdot$H$_{2}$O, FM$\cdot$$\cdot$$\cdot$H$_{2}$O) were generated in a supersonic jet expansion and probed using both chirped-pulse and cavity Fourier transform microwave spectroscopy. The experimental results, supported by ab initio molecular orbital calculations, allow comparing the conformational preferences and the role of the sulfur and oxygen atoms in the O-H$\cdot$$\cdot$$\cdot$O/O-H$\cdot$$\cdot$$\cdot$S/S-H$\cdot$$\cdot$$\cdot$O hydrogen bonds (HBs) stabilizing the dimers. In the furfuryl monohydrates (FA$\cdot$$\cdot$$\cdot$H$_{2}$O, FM$\cdot$$\cdot$$\cdot$H$_{2}$O) water behaves as a proton donor to the ring oxygen, in competence with a second HB to the alcohol or thiol side chain\footnote{M.~Juanes, A.~Lesarri, R.~Pinacho, E.~Charro, J.~E.~Rubio, L.~Enriquez, M.~Jaraiz, \textit{Chem.~Eur.~J.}, \textbf{2018}, 24, 1–9, in press}. Different behavior was observed when the ring oxygen is replaced by sulfur atom in the thenyl monohydrates (TA$\cdot$$\cdot$$\cdot$ H$_{2}$O and TM$\cdot$$\cdot$$\cdot$H$_{2}$O) as the water molecule is binding to the side chain and the $\pi$ electronic cloud of the ring. The water motion in both thenyl dimers is detected by tunneling splittings of the rotational transitions, denoting a weaker binding compared to the furfuryl compounds. The alcohol dimers (TA)$_{2}$ and (FA)$_{2}$ again reveal the different HB strengths in the furfuryl and thenyl groups. The alcohol dimer forms a network of two consecutive O-H$\cdot$$\cdot$$\cdot$O hydrogen bonds involving the oxygen ring, while in the thenyl dimer the alcohol group prefers binding to the $\pi$ cloud than to the sulfur atom in the ring. Spectroscopic, structural and computational data will be reported

Dinámica de fotodisociación ultravioleta de agregados de van der Waals con enlaces de hidrógeno : aplicación a Ar-HCl

Tesis de la Universidad Complutense de Madrid, Facultad de Ciencias Físicas, Departamento de Física Teórica I y II, leída el 11-10-2002En este trabajo de tesis se investiga la dinámica de fotodisociación ultravioleta del agregado Ar - HCl mediante cálculos cuánticos exactos de paquete de ondas y cálculos clásicos, en tres dimensiones, suponiendo momento angular total nulo. Para ello se realiza un estudio resuelto en energía de los dos posibles canales de fragmentación de Ar - HCl: fragmentación parcial en H + Ar - Cl y total en H + AR + Cl. El paquete de ondas asintótico ha sido proyectado sobre los estados correspondientes a los distintos fragmentos de la fotólisis, para diferentes energías de excitación en el intervalo del espectro de absorción de Ar - HCl. La probabilidad global del canal de fragmentación parcial resulta ser aproximadamente el 1% del proceso de fotólisis, correspondiendo el 99% restante a la fragmentación total del agregado. El presente estudio proporciona la primera confirmación teórica de la formación de complejos radicales del tipo Rg - X(Rg = gas noble, X = halógeno) como consecuencia de la fotólisis ultravioleta de agregados Rg - HX. Se han calculado distribuciones de energía interna de los radicales Ar - Cl producidos, encontrándose que a energías muy bajas la formación de Ar - Cl domina el proceso de fotodisociación, aunque su intensidad disminuye rápidamente con la energía de excitación. Asimismo, se han calculado distribuciones de energía cinética del hidrógeno correspondiente a la fragmentación total de Ar - HCl; dichas distribuciones presentan una estructura pronunciada de picos, los cuales están asociados a distintos sucesos colisionales del hidrógeno con Ar y Cl antes de disociarse. En las distribuciones cuánticas obtenidas, tanto de fragmentación parcial como de fragmentación total, se observan manifestaciones de interferencia entre distintos estados de los productos. Los resultados de los cálculos clásicos proporcionan una confirmación de estos efectos de interferencia, que explicaría el comportamiento de todas las distribuciones cuánticas calculadas, y podría ser aplicable a la fotólisis ultravioleta de una gran variedad de agregados con enlaces de hidrógenoDepto. de Física TeóricaFac. de Ciencias FísicasTRUEpu

La neurona de Cajal-Retzius

Este trabajo consiste en una revisión bibliográfica sobre la información que se tiene de las neuronas de Cajal-Retzius, su papel fundamental en el desarrollo embrionario de la corteza cerebral y las principales asociaciones patológicas que se relacionan con ellas. Al principio hablaré sobre la citoarquitectura de la corteza cerebral y los tipos neuronales principales que la forman, así como de una pequeña introducción sobre su desarrollo. Finalmente profundizaré en las características morfológicas y funcionales de la célula de Cajal-Retzius que hacen de ésta un factor fundamental en el desarrollo y en la organización de la corteza cerebral

Molecular Recognition, Transient Chirality and Sulfur Hydrogen Bonding in the Benzyl Mercaptan Dimer

The homodimers of transiently chiral molecules offer physical insight into the process of molecular recognition, the preference for homo or heterochiral aggregation and the nature of the non-covalent interactions stabilizing the adducts. We report the observation of the benzyl mercaptan dimer in the isolation conditions of a supersonic jet expansion, using broadband (chirped-pulse) microwave spectroscopy. A single homochiral isomer was observed for the dimer, stabilized by a cooperative sequence of S-H···S and S-H···π hydrogen bonds. The structural data, stabilization energies and energy decomposition describe these non-covalent interactions as weak and dispersion-controlled. A comparison is also provided with the benzyl alcohol dimer.This research was funded by the Spanish Ministerio de Ciencia e Innovación MICINN-FEDER, grants numbers PGC2018-098561-B-C21 and PGC2018-098561-B-C22. The APC were funded by PGC2018-098561-B-C22