Effects of the matrix and intramolecular interactions on the stability of the higher-energy conformers of 2-fluorobenzoic acid.

DFT(B3LYP)/6-311++G(d,p) calculations on 2-fluorobenzoic acid (2FBA) show that the molecule has four conformers: two low energy conformers (forms I and II) with the carboxylic acid group assuming the cis configuration (O=C-O-H dihedral equal to 0°) and two higher-energy conformers (III, IV) with a trans carboxylic group configuration. Isolation of 2FBA monomers in argon or nitrogen matrices allows for the efficient trapping of both low-energy conformers. Narrowband selective near-IR(NIR) excitation of the 2νOH mode of I in both argon and N2 matrices leads to its efficient conversion into conformer III, which is stabilized by an intramolecular O-H···F interaction. On the other hand, upon identical selective vibrational excitation of II no changes could be noticed in the argon matrix spectra, while experiments carried out on N2 matrices showed conversion of II into III. In conformer IV (the expected direct product resulting from NIR excitation of II), the stabilizing O-H···F interaction existing in III is replaced by an O-H···H repulsive interaction, which leads to a barrier separating this form from II that is about one third of that separating III from I. Under these circumstances, once formed by vibrational excitation of II, conformer IV can easily convert to the reactant species by fast tunneling, justifying the apparent inefficiency of the II→IV conversion upon vibrational excitation of II in an argon matrix. On the other hand, the stabilization of the initially formed conformer IV by the N2 matrix (due to OH···N2 interactions) allows this species to survive long enough to allow the IV→III over-the-barrier conversion to be competitive with the IV→IItunneling, justifying the observed net conversion of the NIR excited conformer II into form III in N2 matrix. These results demonstrate as the intramolecular local topology may decisively influence the intrinsic kinetic stability of different conformers of the same molecule. They are also a clear additional evidence of the stabilization of higher-energy trans conformers of carboxylic acids by the N2 matrix medium that has been found before for other molecules of the same family.

Experimental Evidence of Long-Range Intramolecular Vibrational Energy Redistribution through Eight Covalent Bonds: NIR Irradiation Induced Conformational Transformation of E-Glutaconic Acid.

Long-range intramolecular vibrational energy redistribution (IVR) driven conformational changes were investigated in a matrix-isolated open-chain, asymmetrical dicarboxylic acid, E-glutaconic acid. Although the analysis was challenging due to the presence of multiple backbone conformers and short lifetimes of the prepared higher energy cis conformers, it was shown that the selective excitation of the O-H stretching overtone of one of the carboxylic groups can induce the conformational change (trans to cis) of the other carboxylic group, located at the other end of the E-glutaconic acid molecule. This is a direct proof that the IVR process can act through eight covalent bonds in a flexible molecule before the excess energy completely dissipates into the matrix. The lifetime of the prepared higher energy conformers (averaged over the different backbones) was measured to be 12 s.

Matrix isolation infrared spectroscopic study of 4-Pyridinecarboxaldehyde and of its UV-induced photochemistry.

The structure, infrared spectrum, barrier to internal rotation, and photochemistry of 4-pyridinecarboxaldehyde (4PCA) were studied by low-temperature (10K) matrix isolation infrared spectroscopy and quantum chemical calculations undertaken at both Moller-Plesset to second order (MP2) and density functional theory (DFT/B3LYP) levels of approximation. The molecule has a planar structure (Cs point group), with MP2/6-311++G(d,p) predicted internal rotation barrier of 26.6kJmol-1, which is slightly smaller than that of benzaldehyde (~30kJmol-1), thus indicating a less important electron charge delocalization from the aromatic ring to the aldehyde moiety in 4PCA than in benzaldehyde. A complete assignment of the infrared spectrum of 4PCA isolated in an argon matrix has been done for the whole 4000-400cm-1 spectral range, improving over previously reported data. Both the geometric parameters and vibrational frequencies of the aldehyde group reveal the relevance in this molecule of the electronic charge back-donation effect from the oxygen trans lone electron pair to the aldehyde CH anti-bonding orbital. Upon in situ UV irradiation of the matrix-isolated compound, prompt decarbonylation was observed, leading to formation of pyridine.

Quinolone-Hydroxyquinoline Tautomerism in Quinolone 3-Esters. Preserving the 4-Oxoquinoline Structure To Retain Antimalarial Activity.

Recent publications report in vitro activity of quinolone 3-esters against the bc1 protein complex of Plasmodium falciparum and the parasite. Docking studies performed in silico at the yeast Qo site established a key role for the 4-oxo and N-H groups in drug-target interactions. Thus, the possibility of 4-oxoquinoline/4-hydroxyquinoline tautomerism may impact in pharmacologic profiles and should be investigated. We describe the synthesis, structure, photochemistry, and activity against multidrug-resistant P. falciparum strain Dd2 of ethyl 4-oxo-7-methylquinoline-3-carboxylate (7Me-OQE) and ethyl 4-hydroxy-5-methylquinoline-3-carboxylate (5Me-HQE), obtained from diethyl 2-[((3-methylphenyl)amino)methylene]malonate. Theoretically (B3LYP/6-311++G(d,p)), 5Me-HQE and 7Me-OQE show clear preference for the hydroxyquinoline form. The difference between the lowest energy hydroxyquinoline and quinolone forms is 27 and 38 kJ mol(-1), for 5Me-HQE and 7Me-OQE, respectively. Calculations of aromaticity indexes show that in 5Me-HQE both rings are aromatic, while in the corresponding oxo tautomers the nitrogen-containing ring is essentially non-aromatic. The structure of monomeric 5Me-HQE was studied using matrix isolation coupled to FTIR spectroscopy. No traces of 4-oxoquinoline tautomers were found in the experimental IR spectra, revealing that the species present in the crystal, 5Me-HQE·HCl, was lost HCl upon sublimation but did not tautomerize. Continuous broadband irradiation (λ > 220 nm; 130 min) of the matrix led to only partial photodecomposition of 5Me-HQE (ca. 1/3).

Structure and Photochemistry of N-Salicylidene-p-carboxyaniline Isolated in Solid Argon.

Infrared matrix isolation spectroscopy and DFT/B3LYP/6-311++G(d,p) calculations have been used to characterize the conformational space of the enol-imine and keto-amine tautomers of N-salicylidene-p-carboxyaniline (SCA) in both their E and Z isomeric forms. Monomers of SCA were isolated in an argon matrix (15 K), which was shown to contain only the most stable conformer of the E-enol isomer of the compound. The matrix-isolated E-enol was then subjected to in situ UV irradiation (λ = 335; 345 nm, provided by a laser/MOPO system, or λ > 235 nm, provided by a Hg(Xe) broad-band source), and the photoinduced processes probed by infrared spectroscopy. Two photoreaction channels were observed, with a branching ratio of ∼1:1, corresponding to E-enol → Z-enol isomerization and E-enol → E-keto tautomerization. Both processes were found to be rather effective, with practically complete consumption of the reactant after broad-band irradiation by 1 min only. Identification among the photoproduced species of the Z-enol conformer that differs from the reactant only by E-to-Z isomerization suggests the initial photoproduction of this conformer, which subsequently decays into the lowest energy Z-enol conformer (also identified experimentally). The E-enol → E-keto tautomerization requires an excited state intramolecular proton transfer and twisting about the exocyclic CC bond of the molecule. These processes most probably take place sequentially. However, in the present study the Z-keto isomer, which should act as intermediate in this sequence of processes, could not be detected, most probably due to its short lifetime under the used experimental conditions. On the contrary, the detailed structural and vibrational characterization of the photoproduced E-keto form was successfully achieved.

Infrared Spectrum and UV-Induced Photochemistry of Matrix-Isolated 5-Hydroxyquinoline.

The structure, infrared spectrum, and photochemistry of 5-hydroxyquinoline (5HQ) were studied by matrix isolation infrared spectroscopy, complemented by theoretical calculations performed at the DFT(B3LYP)/6-311++G(d,p) level of approximation. According to the calculations, the trans conformer of 5HQ (with the OH group pointing to the opposite direction of the pyridine ring of the molecule) is more stable than the cis form (by ∼8.8 kJ mol(-1)). The main factors determining the relative stability of the two conformers were rationalized through natural bond orbital (NBO) and charge density analyses. The compound was trapped in solid nitrogen at 10 K, and its infrared spectra registered and interpreted, showing the sole presence in the matrix of the more stable trans conformer. Broadband in situ UV irradiations (λ ≥ 288 nm and λ ≥ 235 nm) allowed for the observation of different chemical transformations, which started by excitation to the S1 state of 5HQ, followed by homolytic cleavage of the O-H bond, and subsequent reattachment of the H atom to the 5HQ radical to form quinolin-5(6H)-one and quinolin-5(8H)-one. The first of these two quinolinones was found to convert to open-ring isomeric ketenes, especially when irradiation was performed at higher energy, whereas the second is rather stable under the used experimental conditions. As a whole, the observed photochemistry of matrix-isolated 5HQ closely matches those previously reported for phenol and thiophenol. A detailed mechanistic interpretation for the observed photochemical processes is here proposed, which received support from time-dependent DFT calculations.

Trans- and cis-stilbene isolated in cryogenic argon and xenon matrices.

Monomers of trans- (TS) and cis-stilbene (CS) were isolated in cryogenic argon and xenon matrices, and their infrared (IR) spectra were fully assigned and interpreted. The interpretation of the vibrational spectra received support from theoretical calculations undertaken at the DFT(B3LYP)/6-311++G(d,p) level of theory. In situ broadband UV irradiation of the matrix-isolated CS led to its isomerization to TS, which appeared in the photolysed matrices in both non-planar and planar configurations. The non-planar species was found to convert into the more stable planar form upon subsequent annealing of the matrices at higher temperature. TS was found to be photostable under the used experimental conditions. The structure of the non-planar TS form was assigned based on the comparison of its observed IR spectrum with those theoretically predicted for different conformations of TS. Chemometrics was used to make this assignment. Additional reasoning on the structure of the studied stilbenes is presented taking as basis results of the Natural Bond Orbital analysis.

Near-infrared and ultraviolet induced isomerization of crotonic acid in N2 and Xe cryomatrices: first observation of two high-energy trans C-O conformers and mechanistic insights.

E-crotonic acid was isolated in cryogenic solid N2 and xenon matrices, and subjected to Laser ultraviolet (UV) and near-infrared (NIR) irradiations. In the deposited matrices, the two low-energy cis C-O E-cc and E-ct conformers, which are the only forms significantly populated in the gas phase, were observed. UV irradiation (λ= 250 nm) of the compound in N2 matrix allows for experimental detection, not just of the two low-energy cis C-O isomers of Z-crotonic acid previously observed in the experiments carried out in argon matrix [Z-cc and Z-ct; R. Fausto, A. Kulbida, and O. Schrems, J. Chem. Soc., Faraday Trans. 91, 3755-3770 (1995)] but also of the never observed before high-energy forms of both E- and Z-crotonic acids bearing the carboxylic acid group in the trans arrangement (E-tc and Z-tc conformers). In turn, NIR irradiation experiments in the N2 matrix allow to produce the high-energy E-tc trans C-O conformer in a selective way, from the initially deposited E-cc form. The vibrational signatures of all the 6 rotameric structures of the crotonic acids experimentally observed, including those of the new trans C-O forms, were determined and the individual spectra fully assigned, also with support of theoretically obtained data. On the other hand, as found before for the compound isolated in argon matrix, the experiments performed in xenon matrix failed to experimental detection of the trans C-O forms. This demonstrates that in noble gas matrices these forms are not stable long enough to allow for their observation by steady state spectroscopy techniques. In these matrices, the trans C-O forms convert spontaneously into their cis C-O counterparts, by tunnelling. Some mechanistic details of the studied processes were extracted and discussed.

Crystal structure, matrix-isolation FTIR, and UV-induced conformational isomerization of 3-quinolinecarboxaldehyde.

The crystal structure of 3-quinolinecarboxaldehyde (3QC) has been solved, and the compound has been shown to crystallize in the space group P21/c (monoclinic) with a = 6.306(4), b = 18.551(11), c = 6.999(4) Å, ß = 106.111(13)°, and Z = 4. The crystals were found to exhibit pseudomerohedral twinning with a twin law corresponding to a two-fold rotation around the monoclinic (100) reciprocal lattice axis (or [4 0 1] in direct space). Individual molecules adopt the syn conformation in the crystal, with the oxygen atom of the aldehyde substituent directed toward the same side of the ring nitrogen atom. In the gas phase, the compound exists in two nearly isoenergetic conformers (syn and anti), which could be successfully trapped in solid argon at 10 K, and their infrared spectra are registered and interpreted. Upon in situ irradiation of matrix-isolated 3QC with UV light (λ > 315 nm), significant reduction of the population of the less stable anti conformer was observed, while that of the conformational ground state (syn conformer) increased, indicating occurrence of the anti → syn isomerization. Upon irradiation at higher energy (λ > 235 nm), the syn → anti reverse photoreaction was observed. Interpretation of the structural, spectroscopic, and photochemical experimental data received support from quantum chemical theoretical results obtained at both DFT/B3LYP (including TD-DFT investigation of excited states) and MP2 levels, using the 6-311++G(d,p) basis set.

Methylparaben isolated in solid argon: structural characterization and UV-induced conversion into methylparaben radical and isomeric ketenes.

Methylparaben (methyl p-hydroxybenzoic acid; MP) is a widely used antimicrobial preservative, being the most frequently used antimicrobial preservative in cosmetics. The generalized use of MP has become controversial, with several recent reports of dangerous side effects. For example, the presence of MP in human breast tumors and its harmful effects on human skin exposed to the sunlight have been demonstrated. In spite of the important practical relevance of the compound and of the controversy about its practical use, its structural and photochemical characterization had not been undertaken hitherto. To fill this gap, in the present study, MP was isolated in solid argon (T = 15 K) and structurally characterized by a combined infrared spectroscopy/quantum chemistry approach. The potential energy surface (PES) of the molecule was investigated in detail, revealing the existence of two almost isoenergetic (ΔE(0) = 0.37 kJ mol(-1)) s-cis carboxylic ester low-energy conformers, with an estimated population ratio in the gas phase at room temperature (∼298 K) of ca. 0.83. The calculations also predicted the existence of two high-energy (ΔE(0) = ∼50 kJ mol(-1)) s-trans carboxylic ester conformers of MP. Upon isolation of the compound in an argon matrix, only the lowest energy conformer was found to survive, due to occurrence of extensive conformational cooling during matrix deposition. The infrared spectrum of this conformer was obtained and interpreted. In addition, the chemical processes resulting from in situ irradiation of the matrix-isolated MP with a broadband UV source (λ > 234 nm) were investigated, revealing extensive conversion of MP into highly reactive methylparaben radical and isomeric ketenes. These observations support the recent concerns regarding uses of MP, in particular when the compound has to be exposed to UV light.

FTIR investigation of the O-H···Xe interaction in simple carboxylic acids in solid xenon.

The O-H stretching region of the infrared spectra of a series of carboxylic acids in Xe matrices was investigated as a function of temperature. Upon increasing the temperature, the νO-H band site-components undergo reversible frequency blue-shifts, which are larger for the lowest-frequency components. This unprecedented observation indicates both that different types of O-H···Xe specific interactions occur, depending on different trapping sites, and the prevalence of stronger interactions of this type for molecules trapped in sites corresponding to lower frequency νO-H band site-components. These results are in agreement with previous investigations pointing to an increased stabilization and larger νO-H frequency red-shifts in carboxylic acid∕Xe complexes bearing a specific H-bond like O-H···Xe interaction. O-H···Xe interaction energies were obtained theoretically and also estimated from the spectroscopic data. Changes in the interaction energies upon temperature variation were also evaluated.

Using heavy atom rare gas matrix to control the reactivity of 4-methoxybenzaldehyde: a comparison with benzaldehyde.

Different patterns of photochemical behavior were observed for 4-methoxybenzaldehyde (p-anisaldehyde) isolated in xenon and in argon matrices. Monomers of the compound isolated in solid Xe decarbonylate upon middle ultraviolet irradiation, yielding methoxybenzene (anisole), and CO. On the other hand, p-anisaldehyde isolated in an Ar matrix and subjected to identical irradiation, predominantly isomerizes to the closed-ring isomeric ketene (4-methoxycyclohexa-2,4-dien-1-ylidene) methanone. Experimental detection of a closed-ring ketene photoproduct, generated from an aromatic aldehyde, constitutes a rare observation. The difference between the patterns of photochemical transformations of p-anisaldehyde isolated in argon and xenon environments can be attributed to the external heavy-atom effect, where xenon enhances the rate of intersystem crossing from the singlet to the triplet manifold in which decarbonylation (via p-methoxybenzoyl radical) takes place. The parent compound, benzaldehyde, decarbonylates (to benzene + CO) when subjected to middle ultraviolet irradiation in both argon and xenon matrices. This demonstrates the role of the methoxy p-anisaldehyde substituent in activation of the reaction channel leading to the formation of the ketene photoproduct.

Photorotamerization of matrix-isolated acrylic acid revisited.

In this study, the conformational preferences and photochemistry of acrylic acid (AA, CH(2)=CHCOOH) monomer isolated in cryogenic argon and krypton matrices were interpreted, based on results of quantum chemical calculations. Natural bond orbital analysis allowed to shed light on the main electronic effects determining the relative stability of the conformers of the molecule in the ground electronic state. The conformational isomerization taking place upon UV-irradiation of the matrix-isolated compound (λ ∼ 243 nm) was explained, based on theoretical complete active space self-consistent field/complete active space with second order perturbation theory (CASSCF/CASPT2) and time-dependent density functional theory (TD-DFT) results, allowing to rationalize the nearly equal populations of the two lowest energy conformers of the molecule observed in the photostationary state. Besides, details of the infrared spectra of the compound were reinterpreted based on the calculated spectra for the two most stable conformers of the molecule. In particular, the assignments for the out-of-plane A" symmetry vibrations were revised.

Photoisomerization and photochemistry of matrix-isolated 3-furaldehyde.

3-Furaldehyde (3FA) was isolated in an argon matrix at 12 K and studied using FTIR spectroscopy and quantum chemistry. The molecule has two conformers, with trans and cis orientation of the O=C-C=C dihedral angle. At the B3LYP/6-311++G(d,p) level of theory, the trans form was computed to be ca. 4 kJ mol(-1) more stable than the cis form. The relative stability of the two conformers was explained using the natural bond orbital (NBO) method. In fair agreement with their calculated relative energies and the high barrier of rotamerization (ca. 34 kJ mol(-1) from trans to cis), the trans and cis conformers were trapped in an argon matrix from the compound room temperature gas phase in proportion ~7:1. The experimentally observed vibrational signatures of the two forms are in a good agreement with the theoretically calculated spectra. Broad-band UV-irradiation (λ > 234 nm) of the matrix-isolated compound resulted in partial trans → cis isomerization, which ended at a photostationary state with the trans/cis ratio being ca. 1.85:1. This result was interpreted based on results of time-dependent DFT calculations. Irradiation at higher energies (λ > 200 nm) led to decarbonylation of the compound, yielding furan, cyclopropene-3-carbaldehyde, and two C(3)H(4) isomers: cyclopropene and propadiene.

Thermal and photoinduced control of relative populations of 4-methoxybenzaldehyde (p-anisaldehyde) conformers.

Two almost isoenergetic conformers of 4-methoxybenzaldehyde (p-anisaldehyde), O-trans and O-cis, are nearly equally populated in gas phase at room temperature. The existence of these two conformers of similar energy makes p-anisaldehyde an attractive molecule for conformational investigations, in which the relative populations of the two forms might be subjected to optical control. In the present study, monomers of the compound were trapped from the room-temperature gas phase into cryogenic argon and xenon matrices. The initial relative amount of the two conformers present in the freshly deposited matrices is shifted slightly in favor of the O-trans conformer. The ratio of the two forms could be reversibly varied by irradiating the sample with UV light in different wavelength ranges or by using the temperature variation. Increasing the temperature of the xenon matrix up to ca. 57 K led to conversion of the less stable O-cis form into the O-trans conformer, shifting the O-cis/O-trans ratio to ca. 1:7. A series of UV irradiations with different long-pass cutoff filters was carried out. UV excitation induced transformation of O-cis and O-trans conformers into each other. These transformations were leading to the UV-wavelength-specific photostationary equilibria characterized by the O-cis/O-trans ratios of about 1:2.2, 1:1.4, 1:1.1, and 1:0.89 for lambda > 328, 295, 288, and 234 nm cutoff filters, respectively. The isomerization processes were probed by infrared spectroscopy and supported by quantum chemical calculations. The absorption bands observed in the infrared spectra of p-anisaldehyde isolated in argon and xenon matrices were assigned to the theoretically predicted normal modes.

FTIR spectroscopic and theoretical study of the photochemistry of matrix-isolated coumarin.

The infrared spectrum of monomeric unsubstituted coumarin (C9H6O2; 2H-1-benzopyran-2-one), isolated in solid argon at 10 K is presented and assigned. The UV-induced (lambda>200 nm) unimolecular photochemistry of the matrix-isolated compound was studied experimentally. Three main photoreactions were observed: (a) decarboxylation of the compound and formation of benzocyclobutadiene and CO2, with the Dewar form of coumarin as intermediate; (b) isomerization of the compound, leading to production of a conjugated ketene; and (c) decarbonylation, leading to formation of CO and benzofuran complex. Further decomposition of benzofuran to produce ethynol is suggested. Photochannels (a) and (b) correspond to those previously observed for matrix-isolated alpha-pyrone and its sulfur analogs (Phys. Chem. Chem. Phys. 2004, 6, 929; J. Phys. Chem. A 2006, 110, 6415), while route (c) is similar to the UV-induced photochemistry of coumarin in the gaseous phase (J. Phys. Chem. A 2000, 104, 1095). Interpretation of the experimental data is supported by extensive calculations performed at the B3LYP/6-311++G(d,p), MP2/6-31G(d,p) and MP2/6-311++G(d,p) levels.