Ana Borba

Chirality influence on the aggregation of methyl mandelate

The methyl ester of mandelic acid is investigated by a wide range of techniques to unravel its aggregation pattern and the influence of relative chirality of the aggregating monomers. Matrix isolation confirms that a single monomer conformation prevails. The electronic spectrum of the dimers is strongly affected by the relative monomer chirality. Vibrational effects are more subtle and can be explained in terms of the most stable homo- and heteroconfigurational dimer structures, when compared to results of MP2 and DFT-D computations. Selective IR/UV double resonance techniques and wide-band FTIR spectroscopy provide largely consistent spectroscopic fingerprints of the chirality discrimination phenomena. The dominant homochiral dimer has two intermolecular O–H⋯OC hydrogen bonds whereas the more strongly bound heterochiral dimer involves only one such hydrogen bond. This is a consequence of the competition between dispersion and intramolecular or intermolecular hydrogen bonding. Aromatic interactions also play a role in trimers and larger clusters, favoring homochiral ring arrangements. Analogies and differences to the well-investigated methyl lactate system are highlighted. Bulk phases show a competition between different hydrogen bond patterns. The enantiopure, racemic, and 3 : 1 crystals involve infinite hydrogen-bonded chains with different arrangements of the aromatic groups. They exhibit significantly different volatility, the enantiopure compound being more volatile than the racemic crystal. The accumulated experimental and quantum-chemical evidence turns methyl mandelate into a model system for the role of competition between dispersion forces and hydrogen bond interactions in chirality discrimination.

Rotational isomers of lactic acid: first experimental observation of higher energy forms

Lactic acid {2-hydroxypropionic acid [CH(CH3)OHCOOH]} monomer was studied by matrix isolation FT-IR spectroscopy and molecular orbital calculations undertaken at both DFT(B3LYP)/6-311++G(d,p) and MP2/6-31G(d,p) levels of approximation. The theoretical calculations predicted the conformer (SsC) with the carboxylic group and both the CCOH(alcohol) and OCCO moieties in a cis configuration as the most stable form. In this conformer, the α-hydroxy hydrogen atom is involved in an intramolecular hydrogen bond with the carbonyl oxygen atom. The second most stable conformer (GskC) also shows a cis carboxylic group and differs from SsC in the CCOH(alcohol) and OCCO dihedral angles, which are equal to 43.3° and 156.8° respectively. These angles are equal to −51.5° and −149.9° in the third most stable conformer (G′sk′C). These forms are characterized by showing a relatively weak intramolecular H(alcohol)⋯O(acid) hydrogen bond. In the AaT conformer, the carboxylic group is trans and the CCOH(alcohol) and OCCO dihedral angles are 162.2° and 174.1°, respectively. This conformer shows a relatively strong H(acid)⋯O(alcohol) hydrogen bond. In consonance with the theoretical results, the matrix isolation experiments confirmed the predominance of conformer SsC in argon and xenon matrices, and provide the first experimental evidence of conformers GskC and AaT. Since the barrier for interconversion G′sk′C ↔ GskC is only ∼2 kJ mol−1, these two conformers are in equilibrium in the matrices and, at low temperature, the population of the less stable G′sk′C form is too small to enable its observation. Full assignment of the observed spectra was undertaken on the basis of comparison with the theoretical data and temperature variation studies. Water doping of matrices enabled the identification of spectral features due to weakly bound complexes of lactic acid with water.

Low Temperature Infrared Spectroscopy Study of Pyrazinamide: From the Isolated Monomer to the Stable Low Temperature Crystalline Phase

A structural and spectroscopic analysis of the anti-tuberculosis drug pyrazinamide (PZA) was carried out. The PZA molecule was predicted theoretically to possess two conformers differing by internal rotation around the C-C( horizontal lineO) bond, with the E conformer (C(s) symmetry point group; N-C-C horizontal lineO dihedral: 180 degrees ) being ca. 30 kJ mol(-1) more stable than the Z form (C(1) point group; N-C-C horizontal lineO dihedral: ca. +/- 42 degrees ). In consonance with both the large energy difference and low energy barrier between the Z and E conformers, upon isolation in low temperature argon and xenon matrices, only the E form could be observed and characterized spectroscopically. In the argon matrix, this conformer was found to exist in at least three matrix sites, of different stability. In a supersonic jet, besides the monomer (E), the most stable dimer of PZA with two equivalent NH...O horizontal line hydrogen bonds could also be identified. Its spectrum reveals rapid energy flow out of the excited NH stretching mode mediated by one of the heteroatoms in the ring. Finally, the IR spectra of the amorphous solid resulting from fast cooling of the vapor of the compound (initially in the alpha crystalline phase) onto the cold substrate of the cryostat (10 K) and of the crystalline phase resulting from warming the amorphous solid were also recorded and interpreted. The obtained crystalline phase was found to be the thermodynamically most stable delta polymorph of PZA.

Molecular Structure, Infrared Spectra, and Photochemistry of Isoniazid under Cryogenic Conditions

In this study, the structure, spectroscopy, and photochemistry of isoniazid (C6H7N3O, INH) were studied by low-temperature infrared spectroscopy and quantum chemistry calculations. According to DFT(B3LYP)/6-311++G(d,p) calculations, 12 minima were found on the potential energy surface of the molecule, corresponding to two cis conformers about the O=C-N-N axis (C1, C2) and one form trans about this axis (T), all being 4-fold degenerate by symmetry. The C1 conformer was predicted to be more stable than T and C2, by 20.4 and 22.6 kJ mol(-1), respectively. In consonance with these results, only C1 could be observed in low-temperature argon and xenon matrixes as well as in the neat glassy state prepared from the vapor of the compound at 70 degrees C. The C1 conformer was also found to be the constituting monomeric unit of the crystalline phase of INH produced from warming of the low-temperature neat amorphous state. The infrared spectra of INH in the different phases studied were fully assigned. After UV (lambda > 235 nm) irradiation of the matrix-isolated isoniazid, the compound was found to undergo photolysis through two different pathways: a Norris type I alpha-cleavage leading to production of isonicotinaldehyde and N2H2 and a concerted sigmatropic reaction with production of pyridine, CO and N2H2. The latter reaction was found to be nearly two times faster than the former in both argon and xenon matrixes. In addition, both reactions were found to be disfavored in a xenon matrix, which is in consonance with the involvement of (n, pi*) excited states in both photochemical processes.

Conformational landscape, photochemistry, and infrared spectra of sulfanilamide.

A combined matrix isolation FTIR and theoretical DFT(B3LYP)/6-311++G(3df,3pd) study of sulfanilamide (SA) was performed. The full conformational search on the potential energy surface of the compound allowed the identification of four different minima, all of them bearing the sulfamide nitrogen atom placed in the perpendicular orientation relatively to the aromatic ring and differing from each other in the orientation of the hydrogen atoms connected to the two nitrogen atoms of the molecule. All conformers were predicted to be significantly populated in the gas phase (at 100 °C, their relative populations were estimated as being 1:0.9:0.3:0.2). However, in agreement with the theoretically calculated low-energy barriers for conformational isomerization, in the low-temperature matrices, only the most stable conformer could be observed, with the remaining forms being converted into this form during matrix deposition (conformational cooling). The unimolecular photochemistry of matrix-isolated SA (in both argon and xenon) was also investigated. Upon broadband UV irradiation (λ > 215 nm), two photofragmentation pathways were observed: the prevalent pathway (A), leading to extrusion of sulfur dioxide and simultaneous formation of benzene-1,4-diamine, which then converts to 2,5-cyclohexadiene-1,4-diimine, and the minor pathway (B), conducting an γ-cleavage plus [1,3] H-atom migration from the sulfamide group to the aromatic ring, which leads to formation of iminosulfane dioxide and aniline, the latter undergoing subsequent phototransformation into cyclohexa-2,5-dien-1-imine. Finally, the crystalline polymorph of SA resulting from warming (265 K) the amorphous solid obtained from fast cooling of the vapor of the compound onto the cold (13 K) substrate of the cryostat was identified spectroscopically, and found to be the γ-crystalline phase, the one exhibiting in average longer H-bonds and an infrared spectrum resembling more that of the low temperature SA glass. Full assignment of the infrared spectra of this crystalline variety as well as of those of the β-polymorph room temperature crystalline sample and low temperature amorphous state was undertaken with help of theoretical results obtained for the crystallographically relevant dimer of SA.

Methylsilsesquioxane-Based Aerogel Systems-Insights into the Role of the Formation of Molecular Clusters.

Condensed clusters of hydrolyzed methyltrimethoxysilane (MTMS) were studied using two complementary approaches: (i) Fourier transform infrared (FTIR) spectroscopy was applied along with the hydrolysis and condensation stages of a sol-gel process from the condensation of colloidal suspension of nanoparticles to the solid phase of bulk material; (ii) density functional theory calculations of energies, structural and vibrational data of pertinent MTMS hydrolysis products, specifically, methylsilanetriol-based species with different number of silicon atoms (from two to eight atoms) and different structures/conformations (linear, cyclic, and cage, in a total of 13 structures), were performed at B3LYP/6-311+G(d,p) level of theory. The calculated infrared spectra show two distinct Si-O-Si stretch vibration bands for models of caged structures. The higher-frequency IR band at ca. 1120 cm(-1) is derived from the antisymmetric Si-O-Si stretch vibration mode, while the lower-frequency band at 1035 cm(-1) is due to the symmetric Si-O-Si stretch and is characteristic of the cyclic clusters, being absent in highly symmetric cage structures. The calculated versus the experimental FTIR spectra of poly(methylsilsesquioxane) (PMSQ) dried aerogel in KBr pellet show that cage/cyclic-like structures prevail over ladder structures (linear) in actual PMSQ.

Amino→Imino Tautomerization upon in Vacuo Sublimation of 2-Methyltetrazole Saccharinate as probed by Matrix Isolation Infrared Spectroscopy

The amino-imino tautomerization of the nitrogen-linked conjugate 2-methyltetrazole-saccharinate (2MTS) was observed upon sublimation of the compound in vacuo. As shown previously by X-ray diffraction [Ismael, A.; Paixão, J. A.; Fausto, R.; Cristiano, M. L. S. J. Mol. Struct., 2011, 1023, 128-142], in the crystalline phase the compound exists in an amino-bridged tautomeric form. Infrared spectroscopic investigation of a cryogenic matrix prepared after sublimation of a crystalline sample of 2MTS and deposition of the sublimate together with argon (in ~1:1000 molar ratio) onto an IR-transparent cold (15 K) substrate, revealed that the form of 2MTS present in the matrix corresponds to the theoretically predicted most stable imino-bridged tautomer. In this tautomer, the labile hydrogen atom is connected to the saccharine nitrogen, and the two heterocyclic fragments are linked by an imino moiety in which the double-bond is established with the carbon atom belonging to the saccharyl fragment. The observed isomeric form of this tautomer is characterized by a zusammen (Z) arrangement of the two rings around the C═N bond of the bridging group and an intramolecular NH···N hydrogen bond. The experimental IR spectrum of the matrix-isolated 2MTS has been fully assigned based on the calculated spectra for the two most stable conformers of this tautomer. A mechanism for the conversion of the tautomeric form existing in the crystal into that present in the gas phase is proposed. As a basis for the interpretation of the experimental results, a detailed theoretical [at the DFT(B3LYP) level of approximation with the 6-31++G(d,p) and 6-311++G(3df,3pd)] study of the potential energy surface of the compound was performed.

Interaction of nicotinamide and picolinamide with phosphatidylcholine and phosphatidylethanolamine membranes: A combined approach using dipole potential measurements and quantum chemical calculations

Interaction between the bioactive compounds nicotinamide and picolinamide and phospholipids (phosphatidylcholines and phosphatidylethanolamines) was investigated by a combined approach using dipole potential measurements and quantum chemical calculations. It is shown that nicotinamide and picolinamide interactions with phosphatidylcholines are of two main types: (i) specific interactions with the phosphate group of the lipid, for which H-bonding between NH(2) group of the substrate and the phosphate plays a dominant role, (ii) conjugated less specific weaker interactions involving both the phosphate and carbonyl groups of the head group, which propagate to the lipid alkyl chains and increase their conformational disorder. For phosphatidylethanolamines, picolinamide was found to decrease the dipole potential of the membrane in a similar way as for phosphatidylcholines, while nicotinamide is ineffective. These findings are correlated with the specific properties of phosphatidylethanolamines (reduced exposure of phosphate groups) and structural differences in the two substrates, in particular: different separation of the nitrogen atoms in the molecules, existence of a strong intramolecular hydrogen bond in picolinamide (NH...N ((ring))), which is absent in nicotinamide, and non-planarity of nicotinamide molecules, in contrast to picolinamide ones. Additional information on the lipid/substrate interactions was extracted from the analysis of the changes produced in the relevant vibrational frequencies of the lipid and substrate upon binding. The present study gives molecular support to the argument that changes of dipole potentials are due to effects on the constitutive dipolar PO and CO groups. In addition, it is also shown that according to the specific binding of the substrate to one or both of those, the conformational state of the acyl chains may be affected. These entropy effects may be in the origin of the well-known interdependence of the properties of one monolayer with respect to the other in bilayer membranes.

Structure and Photochemistry of a Saccharyl Thiotetrazole

The molecular structure and photochemistry of 5-thiosaccharyl-1-methyltetrazole (TSMT) were studied by means of matrix-isolation FTIR spectroscopy, X-ray crystallography, and theoretical calculations. The calculations predicted two conformers of TSMT that differ in energy by more than 15 kJ mol(-1). The infrared spectrum of TSMT isolated in solid argon was fully assigned on the basis of the spectrum calculated (O3LYP/6-311++G(3df,3pd)) for the most stable conformer. In the crystal, TSMT molecules were found to assume the same conformation as for the isolated molecule, with each molecule forming four hydrogen bonds with three neighboring molecules, leading to a network of TSMT oligomers. Upon UV (λ = 265 nm) irradiation of the matrix-isolated TSMT, two photodegradation pathways were observed, both arising from cleavage of the tetrazolyl ring. Pathway a involves cleavage of the N1-N2 and N3-N4 bonds with extrusion of N2, leading to photostable diazirine and thiocarbodiimide derivatives. The photostability of the photoproduced diazirine under the conditions used precluded its rearrangement to the nitrile imine, as reported for 5-phenyltetrazole by Bégué et al. ( J. Am. Chem. Soc. 2012 , 134 , 5339 ). Pathway b involves cleavage of the C5-N1 and N4-N3 bonds, leading to a thiocyanate and methyl azide, the latter undergoing subsequent fragmentation to give CNH.

Spectroscopic characterization of silica aerogels prepared using several precursors – effect on the formation of molecular clusters

Condensed clusters of hydrolyzed tetramethylorthosilicate (TMOS), methyltrimethoxysilane (MTMS) and vinyltrimethoxysilane (VTMS), as single precursors or in combination, were studied using complementary approaches: (i) Fourier transform infrared (FTIR) spectroscopy; (ii) solid-state NMR spectroscopy, and (iii) density functional theory calculations of energies, structural and vibrational and 29Si NMR chemical shift data of pertinent TMOS, MTMS and VMTS hydrolysis products, and species with different numbers of silicon atoms and different structures/conformations (linear, cyclic, and cage), performed at the B3LYP/6-311+G(d,p) and B3LYP/IGLO-III (for NMR) levels of theory. The calculated versus experimental (FTIR and solid-state NMR spectra) analysis of the aerogel derived from a single precursor shows that: (i) the TMOS-derived aerogels are mostly made of linear and/or cyclic elements with silicon environments of types Q4, Q3 and Q1, which have four, three and one Si–O–Si bridges, respectively; (ii) the MTMS-derived aerogels are mainly based on cyclic and/or cage structures with silicon of types T3, T2 and T1; (iii) VTMS-based aerogels exhibit the same type of silicon environments as MTMS (T3, T2 and T1), but incorporate structures that can be linear/cyclic/cage-like. The 29Si NMR spectra of the aerogels prepared with the mixtures of TMOS, MTMS and VTMS allowed the quantification of the relative percentages of the constitutive precursor components in the gels, i.e. the final composition of the aerogel is in line with the composition of the prepared solutions. This result is of utmost importance as the composition of the gel affects its final properties. The integrated experimental and computational investigation on the targeted nanostructured materials reported here provides a new understanding of both the microstructures of aerogels and the condensation stage of sol–gel polymerization.