Molecular and Crystal Structure, Spectroscopy, and Photochemistry of a Dispiro Compound Bearing the Tetraoxane Pharmacophore.

The molecular structure and photochemistry of dispiro[cyclohexane-1,3'-[1,2,4,5]tetraoxane-6',2''-tricyclo[3.3.1.13,7 ]decan]-4-one (TX), an antiparasitic 1,2,4,5-tetraoxane was investigated using matrix isolation IR and EPR spectroscopies, together with quantum chemical calculations undertaken at the DFT(B3LYP)/6-311++G(3df,3pd) level of theory, with and without Grimme's dispersion correction. Photolysis of the matrix-isolated TX, induced by in situ broadband (λ>235 nm) or narrowband (λ in the range 220-263 nm) irradiation, led to new bands in the infrared spectrum that could be ascribed to two distinct photoproducts, oxepane-2,5-dione, and 4-oxohomoadamantan-5-one. Our studies show that these photoproducts result from initial photoinduced cleavage of an O-O bond, with the formation of an oxygen-centered diradical that regioselectivity rearranges to a more stable (secondary carbon-centered)/(oxygen-centered) diradical, yielding the final products. Formation of the diradical species was confirmed by EPR measurements, upon photolysis of the compound at λ=266 nm, in acetonitrile ice (T=10-80 K). Single-crystal X-ray diffraction (XRD) studies demonstrated that the TX molecule adopts nearly the same conformation in the crystal and matrix-isolation conditions, revealing that the intermolecular interactions in the TX crystal are weak. This result is in keeping with observed similarities between the infrared spectrum of the crystalline material and that of matrix-isolated TX. The detailed structural, vibrational, and photochemical data reported here appear relevant to the practical uses of TX in medicinal chemistry, considering its efficient and broad parasiticidal properties.

Structure, Vibrational Spectra, and Cryogenic MatrixPhotochemistry of 6-Bromopyridine-2-carbaldehyde: From the Single Molecule of the Compound to the Neat Crystalline Material.

6-Bromopyridine-2-carbaldehyde (abbreviated as BPCA) is used both as a building block in supramolecular chemistry and as a ligand for transition metal catalysts and luminescent complexes. In this study, the structure and vibrational spectra of BPCA were investigated in both the room temperature neat crystalline phase and for the compound isolated in cryogenic Ar, Kr and Xe matrices. The experimental studies were complemented by quantum chemical DFT(B3LYP)/6-311++G(d,p) calculations. For the crystalline compound, infrared and Raman spectra were obtained and interpreted. Comparison of the obtained infrared spectrum of the crystal with those obtained for the isolated molecules of BPCA in the studied cryomatrices helped to conclude that the intermolecular interactions in the crystal do not significantly perturb the intramolecular vibrational potential. Structural analysis further supports the existence of weak coupling between the intermolecular interactions and the structure of the constituting molecular units in crystalline state. The intermolecular interactions in the BPCA crystal were also evaluated by means of Hirshfeld analysis, which revealed that the most important interactions are weak and of the H…N, H…O, H…H, H…Br and Br…Br types. The conformer of BPCA present in the crystal was found to correspond to the most stable form of the isolated molecule (trans), which bears stabilizing C-H…O=C and C(=O)H…N interactions. This conformer was shown to be the single conformer present in the as-deposited cryogenic matrices prepared from the room temperature gaseous compound. Broadband UV irradiation of matrix-isolated BPCA (λ ≥ 235 nm) resulted in the conversion of the trans conformer into the higher-energy cis conformer, where repulsive C-H…H-C(=O) and C=OLP…LPN (where LP designates a lone electron pair) interactions are present, and decarbonylation of the compound with formation of 2-bromopyridine (plus CO). The decarbonylation reaction was found to be more efficient in the more polarizable Xe matrix, indicating stabilization of the radicals initially formed upon breaking of the C-C(HO) and C-H (aldehyde) bonds in this medium, and testifying the occurrence of the decarbonylation reaction with involvement of radical species. TD-DFT calculations were used to access the nature of the excited states associated with the observed UV-induced reactions. As a whole, this study provides fundamental data to understand the physicochemical behavior of the compound, bridging the properties of the isolated molecule to those of the neat crystalline com-pound. Such information is of fundamental importance for the understanding of the role of BPCA in supramolecular chemistry and to potentiate its applications in synthesis and as a ligand for transition metal catalysts and luminescent complexes.

Matrix Isolation Study of Fumaric and Maleic Acids in Solid Nitrogen.

Fumaric and maleic acids ((E)- and (Z)-HOOC-CH═CH-COOH, FA and MA) were studied experimentally by infrared spectroscopy in nitrogen matrixes and theoretically by quantum chemical calculations. The calculations, carried out at the DFT(B3LYP) and MP2 levels of theory, predicted the existence of at least 5 conformers of maleic acid and 10 conformers of fumaric acid. After the deposition of the matrixes, two conformers of maleic acid (I and II) and three conformers (I-III) of fumaric acid were observed and characterized vibrationally. Selective narrowband near-infrared (NIR) excitation of the first OH stretching overtones of the different conformers of maleic and fumaric acids initially present in the matrixes allowed the generation of higher-energy forms, never before observed experimentally. In the case of maleic acid, conformers I (a cis-trans form, where cis and trans designate the conformation of the carboxylic groups of the molecule) and II (cis-cis) were found to generate the novel conformers VI (trans-trans) and VII (cis-trans), respectively. The conversion of conformer II into the most stable conformer I was also observed. For fumaric acid, the cis-cis conformers I-III were found to give rise to the new cis-trans conformers IV-VII, respectively. The tunneling decay of the new conformers produced upon NIR excitation of the lowest-energy conformers initially trapped in the matrixes was observed, and their lifetimes in solid N2 were determined. The increased stability of all of the observed high-energy conformers of the studied acids in the N2 matrix, compared to the argon matrix, where they could not be observed experimentally, demonstrates the stabilizing effect of the interaction between the OH groups of the acids with the matrix N2 molecules, in line with previous observations for other carboxylic acids. In addition, the photochemistry of matrix-isolated maleic and fumaric acids upon broad-band UV irradiation (λ > 235 nm) was also investigated. UV-induced isomerization of both acids around the C═C double bond was observed, together with their decarboxylation to acrylic acid.

Structure and IR Spectra of 3(5)-Aminopyrazoles and UV-Induced Tautomerization in Argon Matrix.

The prototropic tautomerism in 3(5)-aminopyrazoles was investigated by matrix isolation infrared (IR) spectroscopy, supported by DFT(B3LYP)/6-311++G(d,p) calculations. In consonance with the experimental data, the calculations predict tautomer 3-aminopyrazole (3AP) to be more stable than the 5-aminopyrazole (5AP) tautomer (calculated energy difference: 10.7 kJ mol-1; Gibbs free energy difference: 9.8 kJ mol-1). The obtained matrix isolation IR spectra (in both argon and xenon matrices) were interpreted, and the observed bands were assigned to the tautomeric forms with help of vibrational calculations carried out at both harmonic and anharmonic levels. The matrix-isolated compound (in argon matrix) was then subjected to in situ broadband UV irradiation (λ > 235 nm), and the UV-induced transformations were followed by IR spectroscopy. Phototautomerization of the 3AP tautomer into the 5AP form was observed as the strongly prevalent reaction.

Propiolic Acid in Solid Nitrogen: NIR- and UV-Induced cis → trans Isomerization and Matrix-Site-Dependent trans → cis Tunneling.

Propiolic acid (HCCCOOH, PA) was studied experimentally by infrared spectroscopy in a nitrogen matrix and by ab initio calculations. The vibrational spectra of the cis and trans monomers (O═C-O-H dihedral equal to 0 and 180°, respectively) were measured and assigned. The trans-PA monomer was produced by selective vibrational excitation of the cis-PA monomer molecules trapped in different matrix sites. Broadband in situ UV irradiation (λ > 235 nm) of matrix-isolated PA yielded as product the higher-energy trans conformer, with no other photoproducts being detected. Two cis- cis dimers were also identified in the matrixes and characterized structurally and vibrationally. trans-PA was found to decay back to cis-PA in the dark, by tunneling, and the different lifetimes of the higher-energy PA conformer resulting from pumping different matrix sites and different experimental conditions (using a filter blocking the higher-energy IR radiation of the spectrometer source and without using such a filter) were discussed.

Formic acid dimers in a nitrogen matrix.

Formic acid (HCOOH) dimers are studied by infrared spectroscopy in a nitrogen matrix and by ab initio calculations. We benefit from the use of a nitrogen matrix where the lifetime of the higher-energy (cis) conformer is very long (∼11 h vs. 7 min in an argon matrix). As a result, in a nitrogen matrix, a large proportion of the cis conformer can be produced by vibrational excitation of the lower-energy (trans) conformer. Three trans-trans, four trans-cis, and three cis-cis dimers are found in the experiments. The spectroscopic information on most of these dimers is enriched compared to the previous studies in an argon matrix. The cis-cis dimers of ordinary formic acid (without deuteration) are reported here for the first time. Several conformational processes are obtained using selective excitation by infrared light, some of them also for the first time. In particular, we report on the formation of cis-cis dimers upon vibrational excitation of trans-cis dimers. Tunneling decays of several dimers have been detected in the dark. The tunneling decay of cis-cis dimers of formic acid as well as the stabilization of cis units in cis-cis dimers is also observed for the first time.

Acetic acid-water complex: The first observation of structures containing the higher-energy acetic acid conformer.

Non-covalent interaction of acetic acid (AA) and water is studied experimentally by IR spectroscopy in a nitrogen matrix and theoretically at the MP2 and coupled-cluster with single and double and perturbative triple excitations [CCSD(T)]/6-311++G(2d,2p) levels of theory. This work is focused on the first preparation and characterization of complexes of higher-energy (cis) conformer of AA with water. The calculations show three 1:1 structures for the trans-AA⋯H2O complexes and three 1:1 structures for the cis-AA⋯H2O complexes. Two trans-AA⋯H2O and two cis-AA⋯H2O complexes are found and structurally assigned in the experiments. The two cis-AA⋯ ⋅ H2O complexes are obtained by annealing of a matrix containing water and cis-AA molecules prepared by selective vibrational excitation of the ground-state trans form. The less stable trans-AA⋯H2O complex is obtained by vibrational excitation of the less stable cis-AA⋯H2O complex. In addition, the 1:2 complexes of trans-AA and cis-AA with water molecules are studied computationally and the most stable forms of the 1:2 complexes are experimentally identified.

Acetic acid dimers in a nitrogen matrix: Observation of structures containing the higher-energy conformer.

Acetic acid (AA) dimers are studied experimentally by infrared spectroscopy in a N2 matrix and theoretically at the MP2/6-311++G(2d,2p) level of approximation. This work is focused on the first preparation and characterization of structures containing the higher-energy (cis) conformer of AA. Nine trans-trans, fourteen trans-cis, and six cis-cis dimers are theoretically predicted. Five trans-trans and a number of trans-cis dimers are identified in the experiments, but no indication of cis-cis dimers is found. Two trans-trans dimers and the trans-cis dimers are reported for the first time. One trans-cis dimer is prepared by selective vibrational excitation of the structurally related trans-trans dimer, which converts one of the trans subunits to the cis form. Several trans-cis dimers are obtained by annealing of a matrix containing both trans and cis monomers of AA. Tunneling-induced conversion of the trans-cis dimers into trans-trans forms (including two new trans-trans forms) is observed at low temperatures.

Photochemistry and vibrational spectra of matrix-isolated methyl 4-chloro-5-phenylisoxazole-3-carboxylate.

Methyl 4-chloro-5-phenylisoxazole-3-carboxylate (MCPIC) has been synthesized, isolated in low temperature argon and xenon matrices, and studied by FTIR spectroscopy. The characterization of the low energy conformers of MCPIC was made by undertaking a systematic investigation of the DFT(B3LYP)/6-311++G(d,p) potential energy surface of the molecule. The theoretical calculations predicted the existence of three low energy conformers. Two of them (I and II) were observed experimentally in the cryogenic matrices. The third one (III) was found to be converted into conformer II during deposition of the matrices, a result that is in agreement with the predicted low III → II energy barrier (<0.3 kJ mol(-1)). In situ UV irradiation (λ > 235 nm) of matrix-isolated MCPIC yielded as final photoproduct the corresponding oxazole (methyl 4-chloro-5-phenyl-1,3-oxazole-2-carboxylate). Identification of the azirine and nitrile-ylide intermediates in the spectra of the irradiated matrices confirmed their mechanistic relevance in the isoxazole → oxazole photoisomerization.

Formic and acetic acids in a nitrogen matrix: Enhanced stability of the higher-energy conformer.

Formic acid (HCOOH, FA) and acetic acid (CH(3)COOH, AA) are studied in a nitrogen matrix. The infrared (IR) spectra of cis and trans conformers of these carboxylic acids (and also of the HCOOD isotopologue of FA) are reported and analyzed. The higher-energy cis conformer of these molecules is produced by narrowband near-IR excitation of the more stable trans conformer, and the cis-to-trans tunneling decay is evaluated spectroscopically. The tunneling process in both molecules is found to be substantially slower in a nitrogen matrix than in rare-gas matrices, the cis-form decay constants being approximately 55 and 600 times smaller in a nitrogen matrix than in an argon matrix, for FA and AA respectively. The stabilization of the higher-energy cis conformer is discussed in terms of specific interactions with nitrogen molecule binding with the OH group of the carboxylic acid. This model is in agreement with the observed differences in the IR spectra in nitrogen and argon matrices, in particular, the relative frequencies of the νOH and τCOH modes and the relative intensities of the νOH and νC=O bands.

Conformational space and vibrational spectra of methyl 4-chloro-5-phenyl-1,3-oxazole-2-carboxylate.

Methyl 4-chloro-5-phenyl-1,3-oxazole-2-carboxylate (MCPOC) has been synthesized and isolated in cryogenic matrices (argon and xenon). FTIR spectroscopy studies on the matrix isolated compound, supported by DFT(B3LYP)/6-311++G(d,p) calculations, allow for the identification of two low-energy conformers (I and II) of the molecule, which differ from each other in the orientation of the ester group relative to the oxazole ring. In both these conformers, the ester moiety is in the s-cis configuration (O horizontal lineC-O-CH(3) dihedral: 0 degrees ). Conformer II is ca. 3.0 kJ mol(-1) higher in energy than form I in the gas phase. Two additional higher energy conformers, III and IV, with relative energies of ca. 30 and 45 kJ mol(-1), respectively, were predicted to exist by the calculations, corresponding to structures where the ester group is in an approximately s-trans arrangement. Annealing of the compound isolated in xenon at 60 K led to aggregation and simultaneous reduction of the population of I compared to that of the more polar conformer II. These results suggest the inversion of the order of stability of the two conformers in that matrix, eventually accompanied by a higher trend of conformer I to aggregate. Full assignment of the observed infrared bands to the two experimentally accessible conformers was carried out for the matrix isolated monomeric species. In addition, the infrared spectra of the neat compound in the low-temperature (10 K) amorphous and crystalline phases, as well as the infrared and Raman spectra of the crystal at room temperature were also obtained and assigned.

Matrix isolation and low temperature solid state FTIR spectroscopic study of alpha-furil.

Alpha-furil [C(4)H(3)O-C(=O)-C(=O)-C(4)H(3)O] has been isolated in argon and xenon matrices and studied by FTIR spectroscopy, supported by DFT(B3LYP)/6-311++G(d,p) calculations. The obtained spectra were fully assigned and revealed the presence in the matrices of three different conformers, all of them exhibiting skewed conformations around the intercarbonyl bond with the two C(4)H(3)O-C(=O) fragments nearly planar. The three conformers differ in the orientation of the furan rings relative to the carbonyl groups: the most stable conformer, I (C(2) symmetry; O=C-C=O intercarbonyl dihedral equal to 153.1 degrees), has both furan rings orientated in such a way that one of their beta-hydrogen atoms approaches the oxygen atom of the most distant carbonyl group, forming two H-C=C-C-C=O six-membered rings; the second most stable conformer, II (C(1) symmetry; O=C-C=O intercarbonyl dihedral equal to 126.9 degrees ), has one furan ring orientated as in I, while the second furan group is rotated by ca. 180 degrees (resulting in an energetically less favourable H-C=C-C=O five-membered ring); in the third conformer, III (C(2) symmetry; O=C-C=O dihedral equal to 106.2 degrees ), both furan rings assume the latter orientation relative to the dicarbonyl group. The theoretical calculations predicted the two higher energy forms being 5.85 and 6.22 kJ mol(-1) higher in energy than the most stable form, respectively, and energy barriers for conformational interconversion higher than 40 kJ mol(-1). These barriers are high enough to prevent observation of conformational isomerization for the matrix isolated compound. The three possible conformers of alpha-furil were also found to be present in CCl(4) solution, as well as in a low temperature neat amorphous phase of the compound prepared from fast condensation of its vapour onto a suitable 10 K cooled substrate. On the other hand, in agreement with the available X-ray data [S. C. Biswas, S. Ray and A. Podder, Chem. Phys. Lett., 1987, 134, 541], the IR spectra obtained for the neat low temperature crystalline state reveals that, in this phase, alpha-furil exists uniquely in its most stable conformational state, I.

Conformational flexibility, UV-induced decarbonylation, and FTIR spectra of 1-phenyl-1,2 propanedione in solid xenon and in the low temperature amorphous phase.

1-Phenyl-1,2-propanedione has been isolated in low-temperature xenon matrixes and studied by FTIR spectroscopy, supported by DFT(B3LYP)/6-311++G(d,p) calculations. In good agreement with previous electron diffraction data [Shen, Q.; Hagen, K. J. Phys. Chem. 1993, 97, 985], the calculations predicted the existence of only one stable conformation for the compound, in which the O=C-C=O dihedral angle is 135.6 degrees. On the other hand, the experimental data clearly reveals that, in the as-deposited xenon matrixes (T = 20 K), there is a distribution of molecules with different O=C-C=O dihedral angles around the equilibrium value. This distribution results from the efficient trapping of the conformational distribution existing in the gas phase, prior to deposition, which is determined by the low frequency, large amplitude torsional vibration around the C-C central bond. Upon annealing to higher temperatures (T approximately 45 K), the initially trapped conformational distribution can be modified in a certain degree, favoring more polar structures (corresponding to smaller O=C-C=O dihedral angles), as a result of the interactions with the matrix media. Irradiation of the matrix with UV light (lambda > 235 nm) led to decarbonylation of the compound, with generation of acetophenone and carbon monoxide, with an almost complete consumption of the reagent after 1100 min of irradiation (k = 2.8 x 10(-2) min.(-1)). Aggregation of the compound resulting from the matrix warming was also investigated, providing useful information for interpretation of the spectroscopic data obtained for the low-temperature amorphous state of the neat compound.