Carlos O. Della Védova

Structures and conformations of carbonyl isocyanates and carbonyl azides. An experimental and theoretical investigation

Abstract The geometric structures and conformational compositions of fluorocarbonyl isocyanate, FC(O)NCO, and fluorocarbonyl azide, FC(O)N 3 , were studied by gas electron diffraction, vibrational spectroscopy and ab initio calculations. Both compounds exist in the gas phase as a mixture of two planar conformers ( C s symmetry), with the cis form (carbonyl CO double bond in the cis position with respect to the NC or NN bond) being lower in energy than the trans rotamer. From the experimental scattering intensities the following geometric parameters ( r a distances and ∠ α , angles with 3σ uncertainties) were derived for the predominating cis structures. FC(O)NCO, 75(12)% cis: CO (isocyanate) = 1.154(8) A, CO (carbonyl) = 1.192(8) A, NC = 1.215(9) A, Cz.sbnd;F = 1.320 A (not refined), NC = 1.388(4) A, CNC = 125.9(11)°, NCO = 128.7(6)°, NCF = 107.8(8)° and NCO = 174.6(25)°. FC(O)N 3 , 90(10)% cis: N β N ω = 1.124(5) A, N α = N β = 1.246(5) A, CO = 1.192 A (not refined), CF = 1.324(3) A, N α C = 1.390(4) A, CN α = N β = 110.9(8)°, N α CO = 129.3(4)°, N α CF = 107.4(15)° and N α = N β N ω = 170.7(27)°. The experimentally obtained energy differences between the two conformers of FC(O)NCO (Δ E (ED) = E trans − E cis = 0.7(3) kcal mol −1 , Δ E (IR) = 0.4(2) kcal mol −1 , Δ E (Raman) = 0.8(3) kcal mol −1 ) and of FC(O)N 3 (Δ E (ED) = 1.3(6) kcal mol −1 , Δ E (IR) = 1.5(4) kcal mol −1 , Δ E (Raman) = 1.3(4) kcal mol −1 ) can be reproduced within their error limits by MP2/6–31G * //HF/6–3G * and MP4SDTQ/6–31G * //HF/6–31G * calculations. HF/6–31G * and MP2/6–31G * approximations overestimate these values. Corresponding ab initio calculations were performed for the parent compounds HC(O)NCO and HC(O)N 3 , which are not stable and cannot be studied in the gas phase.

The gas-phase structure and conformational properties of N-sulfinylimine fluorocarbonylsulphane, FC(O)SNSO

Abstract The conformational composition and geometric structure of FC(O)SNSO have been determined from electron diffraction intensities, vibrational spectra and ab initio calculations. The electron diffraction intensities can only be fitted by a mixture of two planar conformers with the CF bond trans or cis to the SN single bond. In both forms the CS single bond is trans to the NS double bond and the SN single bond is cis to the SO double bond. The conformational composition derived from the electron diffraction experiment, 85(5)% trans (Δ G °(ED) G °(cis) G °(trans)=1.0(2) kcal mol −1 ), is in excellent agreement with the value obtained from matrix IR spectra, 8% trans (Δ G °=1.1(1) kcal mol −1 ). Ab initio methods in the HF approximation predict slightly higher (HF/3-21G*) or lower (HF/6-31G*) values for the energy difference. Inclusion of electron correlation reproduces the experimental value perfectly. The following geometric parameters ( r a distances in A and ∠ α angles in degrees with 3σ uncertainties) were derived for the predominant trans conformer: CO=1.178(5) A, CF=1.342 A (fixed), CS=1.760(16) A, SN=1.689(14) A, SN=1.549(7) A, SO=1.449(3) A, OCS=130.8(6)°, FCS=105.9(5)°, CSN=94.7(9)°, SNS=119.0(11)°, NSO=118.0(17)°. This experimental structure is reproduced reasonably well by HF/3-21G* calculations.

Spectroscopic and theoretical studies of sulfamoil fluoride, FSO2NH2 and N-(fluorosulfonyl) imidosulfuryl fluoride, FSO2NS(O)F2

Abstract FT-IR and Raman spectra of sulfamoil fluoride, FSO 2 NH 2 , and N-(fluorosulfonyl) imidosulfuryl fluoride, FSO 2 NS(O)F 2 , were obtained. The experimental data are compared to results of ab initio and density functional theory (DFT) calculations. According to the theoretical studies the main conformer of FSO 2 NH 2 possesses anti conformation (F–S single bond in anti position with respect to the nitrogen lone pair). The vibrational spectra do not confirm the presence of a second conformer in the gas and liquid phases. They have been interpreted on the basis of C S symmetry. The Raman spectra of the liquid and the gas infrared spectra of FSO 2 NS(O)F 2 have been interpreted in the terms of the existence of a single conformation possessing C 1 symmetry, as determined previously by gas electron diffraction (GED). An assignment of the observed bands is proposed for both molecules.

Structures and conformational properties of trifluoromethylsulfonyl isocyanate, CF3SO2NCO, and trifluoromethylsulfonyl azide, CF3SO2N3

Abstract The geometric structures of trifluoromethylsulfonyl isocyanate, CF 3 SO 2 NCO, and trifluoromethylsulfonyl azide, CF 3 SO 2 N 3 , have been determined by gas electron diffraction and by theoretical methods ( HF 6–31 G ∗ , HF 6–31 G ∗ , MP 2 6–31 G ∗ , B 3 P 91 6–31 G ∗ . Both compounds possess a single conformation with eclipsed or nearly eclipsed orientation of the NCO or N 3 group relative to one SO double bond and dihedral angles o (OSNC) = 4(8)° and o (OSNN) = − 24(6)°. The negative sign indicates that the azide group is rotated towards the CF 3 group. The SN bonds in both compounds are very similar (1.653(5) and 1.668(4) A, respectively). The nitrogen bond angle in the isocyanate (SNC = 126.5(15)°) is larger by 15° than that in the azide (SNN = 111.6(15)°). All theoretical methods reproduce the experimental structures satisfactorily except for the SC and SN bond lengths.

NMR Spectroscopic Parameters of Molecular Systems with Strong Hydrogen Bonds

A series of closed H-bonded molecules that have (or not) delocalized bonds were studied. The dependence of both NMR spectroscopic parameters sigma and J-couplings, and also the energy stability of such molecules with H-bond strength, were analyzed. The selected basic geometrical structure was that of malonaldehyde. From its full optimized geometry, the corresponding geometry of 3-OH propanal was obtained, fixing either the d(O-O) distance or a more extended local geometry and then optimizing the other part of the whole structure. Nitromalonaldehyde and nitromalonamide were also studied because they should have stronger H-bonds and their basic structure is also malonaldehyde. The last one also has electronic effects that may be varied by rotating the amino groups. By doing this it is possible to show that the effects on acidity of donors are more important than the equivalent effects on the basicity of acceptors. It is also shown that J-couplings that involve atoms close to the H-bond have important noncontact contributions that must be included in order to reproduce total J values. Noncontact contributions are more important than the Fermi contact (FC) one for J(O-O) in malonaldehyde. In nitromalonamide all three terms, FC, paramagnetic spin-orbital, and spin-dipolar are of the same order of magnitude when both amino groups are rotated. This does not happen for its planar configuration. Nuclear magnetic shielding of the hydrogen belonging to the H-bond is quite sensitive to it. The magnetic behavior of such hydrogen atom is modified when it is part of a closed H-bonded molecule. Then a relationship between the H-bond strength with the paramagnetic contributions of the shieldings of both atoms, C and O of the donor substructure, was obtained. We have found a cubic correlation between sigma(p) (C) of the C-O donor bond with sigma (H) of the H-bonded hydrogen. It is observed that both the noncontact J-coupling contributions and shieldings on atoms belonging to the donor substructure, give a clear evidence about the presence of the resonance phenomenon in the model compounds that have been studied, malonaldehyde, nitromalonaldehyde, and nitromalonamide.

Syntheses, spectroscopic study and X-ray crystallography of some new phosphoramidates and lanthanide(III) complexes of N-(4-nitrobenzoyl)-N',N''-bis(morpholino)phosphoric triamide.

New phosphoramidates with the formula RC(O)N(H)P(O)X(2), R = 2-NO(2)-C(6)H(4), 3-NO(2)-C(6)H(4) and 4-NO(2)-C(6)H(4), X = N(CH(2)CH(3)) (1)-(3), NC(4)H(8) (4)-(6), and NC(4)H(8)O (7)-(9) were synthesized and characterized by (1)H, (13)C, (31)P NMR and IR spectroscopy, and elemental analysis. The reaction of (9) with hydrated lanthanide(III) nitrate leads to ten- or nine-coordinated complexes, (10)-(13). The crystal structure has been determined for (3), (5), (9), (10) and (13). In contrast to all of the previously reported similar phosphoramidate compounds, the -C(O)-N(H)-P(O) skeleton in the free ligand (9) shows a cisoid conformation, with the C=O and P=O double bonds adopting a nearly syn conformation. Quantum chemical calculations were applied for clarifying this exceptional conformational behavior. The monodentate neutral ligand (9) is coordinated to the metal ions via the phosphoryl O atom, adopting the usual anti conformation between the C=O and P=O groups.

Conformation and structure of acetylisocyanate, CH3C(O) NCO, from electron diffraction and microwave data and ab initio calculations

Abstract The geometric structure of acetylisocyanate has been determined from electron diffraction intensities and rotational constants. In accordance with previous vibrational studies, only the cis conformation (cis position of the vicinal CO and NC double bonds) is observed. Ab initio calculations predict the preference of the cis form by 3.8 kcal mol -1 (HF/6-31G*) and 2.4 kcal mol -1 (MP2/6-31G*) respectively. The following geometric parameters were derived ( r a distances and ∠ α angles, error limits are 2σ values): (CO) mean =1.179(3) A, ΔCOCO (carbonyl)  CO(isocyanate)  0.040 A, (from ab initio), CN=1.199(7) A, NC=1.413(7) A, CC=1.499(11), A, CH=1.090 A (from ab inito), CNC=128.2(13)°, NCC=111.5(4)°, CCO=124.0(23)°, NCO=124.5(23)°, NCO=173.0 (from ab initio), HCH=107.2(22)°.

Pediatric Clinical Pharmacology Studies in Chagas Disease

Chagas disease is a neglected parasitic disease endemic in the Americas. It mainly affects impoverished populations and the acute phase of the infection mostly affects children. Many cases have also been detected in nonendemic countries as a result of recent migratory trends. The chronic phase is relatively asymptomatic, but 30% of patients with chronic infection eventually develop cardiac and digestive complications that commonly lead to death or disability. Only two drugs are available for the treatment of Chagas disease, benznidazole and nifurtimox. These drugs have been shown to be effective in the treatment of both acute and early chronic phases in children, but the pharmacokinetics of these drugs have never been studied in this population. We have set out to conduct a pharmacokinetics study of benznidazole in a pediatric population with Chagas disease. The results of this study are expected to allow better estimation of the optimal doses and schedule of pharmacotherapy for Chagas disease in children.

The molecular structure of N-sulfinyl trimethylsilanamine, (CH3)3SiNSO

Abstract The geometric structure of (CH 3 ) 3 SiNSO in the vapour phase has been determined by gas electron diffraction. The molecule possesses a planar SiNSO skeleton with syn conformation. The Si(CH 3 ) 3 group staggers the NS double bond. The following skeletal parameters ( r a distances and ∠ α angles with 3σ errors limits) were obtained: SiN 1.750(6)A, NS 1.508(5)A, SO 1.444(4)A, SiNS 133.9(9)°, NSO 122.5(10)°. Ab initio calculations ( HF /3−21 G ∗ ) were performed for H 3 SiNSO and confirm the planar syn structure for sulfinyl silanamines.

Raman spectroscopic study of the conformational changes of thyroxine induced by interactions with phospholipid.

Abstract. Comparison of the Raman spectra of thyroxine (L-3,3′,5,5′-tetraiodothyronine) in the pure state and in a 1:5 mixture with phosphatidylcholine reveals spectral differences that reflect structural changes of thyroxine induced by interactions with the phospholipid. These structural changes could be localized in specific parts of the thyroxine molecule on the basis of a vibrational analysis that was carried out by density functional calculations with the B3LYP hybrid functional applying the SDD effective core potential basis set. The calculated (and subsequently scaled) frequencies reveal a good agreement with the experimental data, which together with calculated IR and Raman intensities allow a plausible assignment of most of the IR and Raman bands. Thus, it is found that modes localized in the aromatic β-ring and in the ether group as well as the C-I stretching modes of ring α are affected upon lipid interactions, indicating that thyroxine interacts with the phosphatidylcholine bilayer via penetration of the hydrophobic part of the molecule.