Unravelling the structural features of monosaccharide glyceraldehyde upon mono-hydration by quantum chemistry and rotational spectroscopy.

Water is a fundamental molecule for life, and investigating its interaction with monosaccharides is of great interest in order to understand its influence on their conformational behavior. In this study, we report on the conformational landscape of monosaccharide glyceraldehyde, the simplest aldose sugar, in the presence of a single water molecule in the gas phase. This investigation was performed using a combination of Fourier transform microwave spectroscopy and theoretical calculations. Out of the nine calculated conformers, only the lowest energy conformer was experimentally observed and characterized. Interestingly, the presence of water was found to induce structural features in the lowest energy conformer of the glyceraldehyde monomer, with water positioned between the alcohol groups. To analyze this interaction further, non-covalent interaction plots were employed to map the intermolecular interactions in the observed species. Additionally, natural bond orbital analysis was conducted to study the effects of charge transfer in the monohydrate system. Furthermore, topological analysis based on Bader's Atoms in Molecules theory was performed to gain insights into the observed complex. The results of all three analyses consistently showed the formation of relatively strong hydrogen bonds between water and glyceraldehyde, leading to the formation of a seven-member ring network.

The gas-phase structure determination of α-pinene oxide: An endo-cyclic epoxide of atmospheric interest.

The gas-phase rotational spectra of α-pinene oxide have been recorded using a chirped-pulse Fourier transform microwave spectrometer in the 6-18 GHz frequency range. The parent species and all heavy atom isotopologues (13C and 18O) have been observed in their natural abundance. The experimental rotational constants of all isotopic species observed have been determined and used to obtain the substitution (rs) and the effective (r0) structures of the most stable conformer of α-pinene oxide. Calculations using the density functional theories B3LYP, M06-2X, and MN15-L and the ab initio method MP2 level of theory were carried out to check their performance against experimental results. The structure of the heavy atom's skeleton of α-pinene oxide has been compared to that of α-pinene and has shown that epoxidation does not overly affect the structure of the bicycle, validating its robustness. Furthermore, the structural features have been compared to those of other bicyclic molecules, such as nopinone and ß-pinene.

The conformational landscape of myrtenol: The structure of the hydroxymethyl group and its robustness upon hydration.

The conformational landscape of myrtenol (2-pinen-10-ol) and its robustness upon hydration were investigated theoretically and experimentally by employing a synergic combination of quantum chemical calculations and Fourier transform microwave spectroscopy coupled to a supersonic jet expansion. Relaxed potential energy surfaces have been carried out, and the lowest energy conformers of the monomer were found to be associated with different geometries of the hydroxymethyl group from those previously reported [Sedo et al., J. Mol. Spectrosc. 356, 32 (2019)]. Geometry optimizations and harmonic vibrational frequency calculations allowed characterization of the equilibrium structure of the possible conformers of myrtenol. Among the nine predicted structures, four have been observed, analyzed, and identified. The controversy on the geometry was solved with the deuteration of the hydroxyl group, which led to the determination of substitution (rs) geometry, in agreement with the present theoretical results. Interestingly, the four observed conformers exhibit the same orientation of OH as in the allyl alcohol molecule. Furthermore, hydrogen bonding linking myrtenol to water was studied. One monohydrate has been observed and identified. Non-covalent interactions and natural bond orbital analysis were performed to depict the interactions responsible for the stabilization of the observed structure. We conclude that the structure of the hydroxymethyl group is robust and does not change upon hydration.

Identification of the maze in the conformational landscape of fenchol.

The rotational spectrum of the bicyclic molecule fenchol (C10H18O, 1,3,3-trimethylbicyclo[2.2.1]heptan-2-ol) - a biogenic volatile organic compound - was recorded in the gas phase using an impulse Fourier transform microwave spectrometer coupled to a supersonic jet expansion over the 2-20 GHz range. Quantum chemical calculations were performed to characterize the conformational landscape of the two diastereoisomers, endo-fenchol and exo-fenchol, with respect to the orientation of the hydroxyl group. The three most stable structures for each diastereoisomer were optimized at the MP2/6-311++G(2df,p) level of theory. Two of them were found to be very close in energy. Molecular parameters obtained from the analysis of observed signals led to the observation of one conformer per diastereoisomer. For the endo-fenchol molecule the rs geometry associated with the hydroxyl group was obtained, from the observation and analysis of the rotational spectra associated with the deuterated hydroxyl group. The nuclear quadrupolar hyperfine signature was identified. The hydroxyl group was found to be oriented into the direction of the methyl groups attached to C3, for the more stable conformer of endo-fenchol. For exo-fenchol, it is oriented into the methyl group attached to C1.

The quasi-unchanged gas-phase molecular structures of the atmospheric aerosol precursor ß-pinene and its oxidation product nopinone.

The rotational spectra of the two bicyclic molecules ß-pinene and its oxidation product nopinone were investigated in the gas phase, using Fourier transform microwave spectroscopy coupled to a supersonic jet, in the 2-20 GHz range. The parent species and all heavy atom isotopologues have been observed in their natural abundance. The spectroscopic parameters of the ground states were determined from a Watson's Hamiltonian in the A reduction. The rotational constants were used together with geometrical parameters obtained from ab initio calculations to determine the r0 and r structures of the skeletons, without any structural assumption in the fit concerning the heavy atoms. Comparison with solid phase and other bicyclic monoterpenes unveiled an unprecedented complete set of geometrical parameters for the rigid cages. The structures of ß-pinene and nopinone are very close, except for the substituents at C2. In the gas phase C2 is a centre of planarity in both molecules.

APOBEC3A intratumoral DNA electroporation in mice.

Human APOBEC3A (A3A) cytidine deaminase shows pro-apoptotic properties resulting from hypermutation of genomic DNA, induction of double-stranded DNA breaks (DSBs) and G1 cell cycle arrest. Given this, we evaluated the antitumor efficacy of A3A by intratumoral electroporation of an A3A expression plasmid. DNA was repeatedly electroporated into B16OVA, B16Luc tumors of C57BL/6J mice as well as the aggressive fibrosarcoma Sarc2 tumor of HLA-A*0201/DRB1*0101 transgenic mice using noninvasive plate electrodes. Intratumoral electroporation of A3A plasmid DNA resulted in regression of ~50% of small B16OVA melanoma tumors that did not rebound in the following 2 months without treatment. Larger or more aggressive tumors escaped regression when so treated. As APOBEC3A was much less efficient in provoking hypermutation and DSBs in B16OVA cells compared with human or quail cells, it is likely that APOBEC3A would be more efficient in a human setting than in a mouse model.

Torsion-rotation-vibration effects in the ground and first excited states of methacrolein, a major atmospheric oxidation product of isoprene.

Methacrolein is a major oxidation product of isoprene emitted in the troposphere. New spectroscopy information is provided with the aim to allow unambiguous identification of this complex molecule, characterized by a large amplitude motion associated with the methyl top. State-of-the-art millimeter-wave spectroscopy experiments coupled to quantum chemical calculations have been performed. For the most stable s-trans conformer of atmospheric interest, the torsional and rotational structures have been characterized for the ground state, the first excited methyl torsional state (ν27), and the first excited skeletal torsional state (ν26). The inverse sequence of A and E tunneling sub-states as well as anomalous A-E splittings observed for the rotational lines of v26 = 1 state clearly indicates a coupling between methyl torsion and skeletal torsion. A comprehensive set of molecular parameters has been obtained. The far infrared spectrum of Durig et al. [Spectrochim. Acta, Part A 42, 89-103 (1986)] was reproduced, and a Fermi interaction between ν25 and 2ν27 was evidenced.

Spin-torsion effects in the hyperfine structure of methanol.

The magnetic hyperfine structure of the non-rigid methanol molecule is investigated experimentally and theoretically. 12 hyperfine patterns are recorded using molecular beam microwave spectrometers. These patterns, along with previously recorded ones, are analyzed in an attempt to evidence the effects of the magnetic spin-torsion coupling due to the large amplitude internal rotation of the methyl group [J. E. M. Heuvel and A. Dymanus, J. Mol. Spectrosc. 47, 363 (1973)]. The theoretical approach setup to analyze the observed data accounts for this spin-torsion in addition to the familiar magnetic spin-rotation and spin-spin interactions. The theoretical approach relies on symmetry considerations to build a hyperfine coupling Hamiltonian and spin-rotation-torsion wavefunctions compatible with the Pauli exclusion principle. Although all experimental hyperfine patterns are not fully resolved, the line position analysis yields values for several parameters including one describing the spin-torsion coupling.

The cyclic ground state structure of the HF trimer revealed by far infrared jet-cooled Fourier transform spectroscopy.

The rovibrationally resolved Fourier transform (FT) far infrared (FIR) spectra of two intermolecular librations of (HF)3, namely the in-plane ν6 and out-of-plane ν4 bending fundamentals centered, respectively, at about 494 cm(-1) and 602 cm(-1), have been recorded for the first time under jet-cooled conditions using the supersonic jet of the Jet-AILES apparatus. The simultaneous rotational analysis of 245 infrared transitions belonging to both bands enabled us to determine the ground state (GS), ν6 and ν4 rotational and centrifugal distortion constants. These results provided definite experimental answers to the structure of such a weakly bound trimer: firstly the vibrationally averaged planarity of cyclic (HF)3, also supported by the very small value of the inertia defect obtained in the GS, secondly the slight weakening of the hydrogen bond in the intermolecular excited states evidenced from the center of mass separations of the HF constituents determined in the ground, ν6 = 1 and ν4 = 1 states of (HF)3 as well as the decrease of the fitted rotational constants upon excitation. Finally, lower bounds of about 2 ns on ν6 and ν4 state lifetimes could be derived from the deconvolution of experimental linewidths. Such long lifetimes highlight the interest in probing low frequency intermolecular motions of molecular complexes to get rid of constraints related to the vibrational dynamics of coupled anharmonic vibrations at higher energy, resulting in loss of rotational information.

The far infrared spectrum of naphthalene characterized by high resolution synchrotron FTIR spectroscopy and anharmonic DFT calculations.

Using synchrotron radiation, we performed the rotationally resolved Fourier transform infrared absorption spectroscopy of three bands of naphthalene C10H8, namely ν(46)-0 (centered at 782 cm(-1), 12.7 µm), ν(47)-0 (centered at 474 cm(-1), 21 µm), and ν(48)-0 (centered at 167 cm(-1), 60 µm). The intense CH bending out of plane ν(46)-0 band was recorded under supersonic jet-cooled conditions using a molecular beam (the Jet-AILES apparatus) and the low frequency ν(47)-0 and ν(48)-0 bands were measured at room temperature in a long absorption path cell. The simultaneous rotational analysis of these bands permitted us to refine the ground state (GS) and ν(46) rotational spectroscopic constants and to provide the first sets of constants for the ν(47) and ν(48) modes. The experimental rotational constants were then used as reference data to calibrate theoretical models in order to provide new insights into the accuracy of anharmonic calculations. The B97-1 functional associated with the cc-pVTZ and ANO-RCC basis sets gave a consistent set of results, for rotational constants and fundamental frequencies. The data presented here pave the way for the search of naphthalene through its far-infrared spectrum in different objects of the interstellar medium.

Synchrotron FTIR spectroscopy of weak torsional bands: a case study of cis-methyl formate.

The far infrared spectrum of cis-methyl formate has been recorded on the AILES beamline of the synchrotron SOLEIL using a Fourier transform infrared spectrometer coupled to a long path cell. The very weak fundamental band associated with the methyl-top torsion mode (ν(18)) was observed. The frequency analysis was performed using the "rho axis method", and the microwave and millimeter-wave data from the literature. A precise determination of the band origins (ν(18)(A) = 132.4303 cm(-1) and ν(18)(E) = 131.8445 cm(-1)) and of the barrier height [V(3) = 370.7398 (58) cm(-1)] have been obtained. The intensity of the ν(18) fundamental band was determined to be 3.4 × 10(-21) cm(-1)∕(molecule cm(-2)) at 297 K, equally shared among A-A and E-E transitions, thus leading to a dipole moment component µ(c)(3) equal to 0.0483 D. The results were compared with the ab initio calcula-tions of Senent et al. [Astrophys. J. 627, 567 (2005)].

The (CH2)2O-H2O hydrogen bonded complex. Ab Initio calculations and Fourier transform infrared spectroscopy from neon matrix and a new supersonic jet experiment coupled to the infrared AILES beamline of synchrotron SOLEIL.

A series of hydrogen bonded complexes involving oxirane and water molecules have been studied. In this paper we report on the vibrational study of the oxirane-water complex (CH(2))(2)O-H(2)O. Neon matrix experiments and ab initio anharmonic vibrational calculations have been performed, providing a consistent set of vibrational frequencies and anharmonic coupling constants. The implementation of a new large flow supersonic jet coupled to the Bruker IFS 125 HR spectrometer at the infrared AILES beamline of the French synchrotron SOLEIL (Jet-AILES) enabled us to record first jet-cooled Fourier transform infrared spectra of oxirane-water complexes at different resolutions down to 0.2 cm(-1). Rovibrational parameters and a lower bound of the predissociation lifetime of 25 ps for the v(OH)(b) = 1 state have been derived from the rovibrational analysis of the ν(OH)(b) band contour recorded at respective rotational temperatures of 12 K (Jet-AILES) and 35 K (LADIR jet).

Magnetic hyperfine coupling of a methyl group undergoing internal rotation: a case study of methyl formate.

The hyperfine structure of methyl formate was recorded in the 2-20 GHz range. A molecular beam coupled to a Fourier transform microwave spectrometer having an instrumental resolution of 0.46 kHz and limited by a Doppler width of a few kHz was used. A-type lines were found split by the magnetic hyperfine coupling while no splittings were observed for E-type lines. Symmetry considerations were used to account for the internal rotation of the methyl top and to derive effective hyperfine coupling Hamiltonians. Neglecting the spin-rotation magnetic coupling, the vanishing splittings of the E-type lines could be understood and analyses of the hyperfine patterns of the A-type lines were performed. The results are consistent with a hyperfine structure dominated by the magnetic spin-spin coupling due to the three hydrogen atoms of the methyl group.

Influence of the geometry of a hydrogen bond on conformational stability: a theoretical and experimental study of ethyl carbamate.

Spectra of ethyl carbamate (urethane) in the gas phase have been recorded in the microwave (4-20 GHz), millimeter-wave (49-118 GHz and 150-235 GHz) and mid-infrared (1000-1900 cm(-1)) regions. At the same time, high level ab initio calculations have been performed in order to both predict the experimental results and help in understanding the physical properties of the system. An extensive set of spectroscopic constants for the two most stable conformers in the gas phase, that might be useful for astrophysical databases, has been derived from the observed signals. The most stable conformer has been unambiguously identified. Then, the influence of a weak intramolecular hydrogen bond on the conformational stability has been discussed on the basis of theoretical and experimental results.

The chiral molecule CHClFI: first determination of its molecular parameters by Fourier transform microwave and millimeter-wave spectroscopies supplemented by ab initio calculations.

The rotational spectrum of chlorofluoroiodomethane (CHClFI) has been investigated. Because its rotational spectrum is extremely crowded, extensive ab initio calculations were first performed in order to predict the molecular parameters. The low J transitions were measured using a pulsed-molecular-beam Fourier transform spectrometer, and the millimeter-wave spectrum was measured to determine accurate centrifugal distortion constants. Because of the high resolution of the experimental techniques, the analysis yielded accurate rotational constants, centrifugal distortion corrections, and the complete quadrupole coupling tensors for the iodine and chlorine nuclei, as well as the contribution of iodine to the spin-rotation interaction. These molecular parameters were determined for the two isotopologs CH35ClFI and CH37ClFI. They reproduce the observed transitions within the experimental accuracy. Moreover, the ab initio calculations have provided a precise equilibrium molecular structure. Furthermore, the ab initio molecular parameters are found in good agreement with the corresponding experimental values.

Prerequisites for effective adenovirus mediated gene therapy of colorectal liver metastases in the rat using an intracellular neutralizing antibody fragment to p21-Ras.

Ras mutations are present in 40-50% of colorectal cancers. Inactivating this oncogene may therefore reduce proliferation capacity. In order to target ras we studied the transduction efficacy and anti tumour activity of an adenoviral vector expressing an intracellular, neutralizing single chain antibody to p21-ras (Y28). In in vitro studies transfection levels of the K-ras mutated rat colon carcinoma cell line CC531 were studied using the LacZ marker gene. In our in vivo liver metastases model different routes of administration were evaluated to determine which regimen resulted in the best transfection levels and tumour responses: intravenous injection, intratumoural injection, isolated liver perfusion, or hepatic artery infusion. CC531 cells are readily transfected in vitro, resulting in significant inhibition of tumour cell proliferation by the Y28 construct. Intravenous injection did not result in any measurable transfection. Intratumoural injection resulted only in the transfection of tumour cells along the needle track. IHP as well as single HAI achieved low transfection levels of tumour tissue. Expression of Y28 was demonstrated in tumours after IT injection, HAI and IHP. Whereas, repeated HAI's clearly achieved expression in and around tumour associated vessels. Only five times repeated HAI's with Y28 resulted in a tumour response: in all animals tumour growth was inhibited, and in three rats out of eight a complete regression of the liver tumours was observed.

Biodegradability of volatile hydrocarbons of gasoline.

The biodegradability under aerobic conditions of volatile hydrocarbons (4-6 carbons) contained in gasoline and consisting of n-alkanes, iso-alkanes, cycloalkanes and alkenes, was investigated. Activated sludge was used as the reference microflora. The biodegradation test involved the degradation of the volatile fraction of gasoline in closed flasks under optimal conditions. The kinetics of biodegradation was monitored by CO2 production. Final degradation was determined by gas chromatographic analysis of all measurable hydrocarbons (12 compounds) in the mixture after sampling the headspace of the flasks. The degradation of individual hydrocarbons was also studied with the same methodology. When incubated individually, all hydrocarbons used as carbon sources, except 2,2-dimethylbutane and 2,3-dimethylbutane, were completely consumed in 30 days or less with different velocities and initial lag periods. When incubated together as constituents of the light gasoline fraction, all hydrocarbons were metabolised, often with higher velocities than for individual compounds. Cometabolism was involved in the degradation of dimethyl isoalkanes.

Cancer gene therapy mediated by CTS1, a p53 derivative: advantage over wild-type p53 in growth inhibition of human tumors overexpressing MDM2.

Recently, a new p53 derivative has been designed, namely chimeric tumor suppressor 1 (CTS1), in which the p53 domains that are known to mediate p53 inactivation have been replaced. In this study, the antitumoral activity of CTS1 mediated by adenovirus vector has been evaluated in comparison with a p53 adenovirus vector in various human tumor cell lines. In vitro, in terms of cell growth inhibition, the CTS1 vector was significantly (P < .01) more efficient (2- to 7-fold) than the p53 vector in tumor models overexpressing an inhibitor of p53, murine double minute-2. This result was confirmed in vivo in a pre-established tumor developed in nude mice. In an osteosarcoma model overexpressing murine double minute-2, we have shown a significantly (P < .05) higher tumor growth delay with the CTS1 vector compared with the p53 vector (25.6 days compared with 12.4 days). Furthermore, both in vitro and in vivo, we have shown that this higher inhibition of tumor growth with the CTS1 vector was correlated with a higher induction of apoptosis. Therefore, CTS1 is a potentially improved tumor suppressor gene for the treatment of human tumors resistant to wild-type p53 gene therapy.

Radiosensitization of human tumor cell lines induced by the adenovirus-mediated expression of an anti-Ras single-chain antibody fragment.

The expression of activated ras genes has been implicated as a contributing factor to the radioresistance of tumor cells. As a strategy for compromising Ras protein activity and potentially enhancing the radiosensitivity of tumor cells, we have investigated the application of the AV1Y28 adenovirus, which expresses a single-chain antibody fragment directed against p21 Ras proteins. The ability of AV1Y28 transduction to modulate radioresponse was investigated using four human tumor cell lines--U251 glioblastoma, MIA PaCa-2 pancreatic carcinoma, and the colon carcinomas SW620 and HT29. Cultures were exposed to sufficient levels of AV1Y28 to transduce more than 90% of the cells; 24 h later, cultures were exposed to ionizing radiation, and clonogenic cell survival was determined. Tumor cell survival was reduced by 40-50% when the tumor cell lines were exposed to AV1Y28 only. In addition, for each tumor cell line, AV1Y28 exposure enhanced the level of radiation-induced cell killing. Dose enhancement factors at a surviving fraction of 0.1 ranged from 1.3 to 1.5. Furthermore, for each of the cell lines, the surviving fraction at 2 Gy was significantly reduced by AV1Y28 exposure. In contrast to the results seen in tumor cells, the radiosensitivity of a normal human fibroblast cell line was not affected by AV1Y28. These data indicate that this anti-Ras adenovirus enhances the radiosensitivity of tumor cells but does not affect the radiosensitivity of normal cells.

Betulinic acid derivatives: a new class of specific inhibitors of human immunodeficiency virus type 1 entry.

A novel series of omega-aminoalkanoic acid derivatives of betulinic acid were synthesized and evaluated for their activity against human immunodeficiency virus (HIV). The anti-HIV-1 activity of several members of this new series was found to be in the nanomolar range in CEM 4 and MT-4 cell cultures. The optimization of the omega-aminoalkanoic acid side chain is described. The presence of an amide function within the side chain was found important for optimal activity. RPR 103611 (14g), a statine derivative, was found to be inactive against HIV-1 protease, reverse transcriptase, and integrase as well as on gp120/CD4 binding. "Time of addition" experiments suggested interaction with an early step of HIV-1 replication. As syncytium formation, but not virus-cell binding, seems to be affected, betulinic acid derivatives are assumed to interact with the postbinding virus-cell fusion process.