Silmar A. do Monte

Dynamic Effects Dictate the Mechanism and Selectivity of Dehydration–Rearrangement Reactions of Protonated Alcohols [Me2(R)CCH(OH2)Me]+ (R=Me, Et, iPr) in the Gas Phase

The gas-phase dehydration-rearrangement (DR) reactions of protonated alcohols [Me2 (R)CCH(OH2 )Me](+) [R=Me (ME), Et (ET), and iPr (I-PR)] were studied by using static approaches (intrinsic reaction coordinate (IRC), Rice-Ramsperger-Kassel-Marcus theory) and dynamics (quasiclassical trajectory) simulations at the B3LYP/6-31G(d) level of theory. The concerted mechanism involves simultaneous water dissociation and alkyl migration, whereas in the stepwise reaction pathway the dehydration step leads to a secondary carbocation intermediate followed by alkyl migration. Internal rotation (IR) can change the relative position of the migrating alkyl group and the leaving group (water), so distinct products may be obtained: [Me(R)CCH(Me)Me⋅⋅⋅OH2 ](+) and [Me(Me)CCH(R)Me⋅⋅⋅OH2 ](+) . The static approach predicts that these reactions are concerted, with the selectivity towards these different products determined by the proportion of the conformers of the initial protonated alcohols. These selectivities are explained by the DR processes being much faster than IR. These results are in direct contradiction with the dynamics simulations, which indicate a predominantly stepwise mechanism and selectivities that depend on the alkyl groups and dynamics effects. Indeed, despite the lifetimes of the secondary carbocations being short (<0.5 ps), IR can take place and thus provide a rich selectivity. These different selectivities, particularly for ET and I-PR, are amenable to experimental observation and provide evidence for the minor role played by potential-energy surface and the relevance of the dynamics effects (non-IRC pathways, IR) in determining the reaction mechanisms and product distribution (selectivity).

Revisiting the concept of the (a)synchronicity of diels‐alder reactions based on the dynamics of quasiclassical trajectories

A number of model Diels‐Alder (D‐A) cycloaddition reactions (H2CCH2 + cyclopentadiene and H2CCHX + 1,3‐butadiene, with X = H, F, CH3, OH, CN, NH2, and NO) were studied by static (transition state ‐ TS and IRC) and dynamics (quasiclassical trajectories) approaches to establish the (a)synchronous character of the concerted mechanism. The use of static criteria, such as the asymmetry of the TS geometry, for classifying and quantifying the (a)synchronicity of the concerted D‐A reaction mechanism is shown to be severely limited and to provide contradictory results and conclusions when compared to the dynamics approach. The time elapsed between the events is shown to be a more reliable and unbiased criterion and all the studied D‐A reactions, except for the case of H2CCHNO, are classified as synchronous, despite the gradual and quite distinct degrees of (a)symmetry of the TS structures.

Photochemical Deactivation Process of HCFC-133a (C2H2F3Cl): A Nonadiabatic Dynamics Study

The photochemical deactivation process of HCFC-133a (C2H2F3Cl) was investigated by computing excited-state properties with a number of single-reference methods, including coupled cluster to approximated second order (CC2), algebraic diagrammatic construction to second order (ADC(2)), and time-dependent density functional theory (TDDFT). Excited states calculated with these methods, especially TDDFT, show good agreement with our previous multireference configuration interaction (MR-CISD) results. All tested methods were able to correctly predict the properties of the main series of excited states, the n-σ*, n-4p, and n-4s. Nonadiabatic dynamics in the gas phase considering 14 electronic states was simulated with TDDFT starting at the 10 ± 0.25 eV spectral window, to be compared to experimental data measured after 123.6 nm excitation. The excited-state lifetime is 137 fs. Internal conversion to the ground state occurred through several different reaction pathways with different products, including atomic elimination (Cl, F, or H), multifragmentation mechanisms (Cl+F, Cl+H, or F+H), and CC bond-fission mechanisms (alone or with Cl or H elimination). The main photochemical channels observed were Cl, Cl+H, and Cl+F eliminations, representing 54% of all processes.

Ab initio and DFT conformational study on N-nitrosodiethylamine, (C2H5)2N-N=O

AbstractAb initio (MP2) and DFT (B3LYP) calculations, using the cc-pVTZ and aug-cc-pVTZ basis sets, have been performed to characterize some stationary points on the ground state potential energy surface of the title molecules. Several properties as, for instance, relative energies, the barriers for NO rotation around the NN bond, NBO charges on O and amino N atoms, as well as the dipole moments, have been calculated and analyzed in the light of the structures found. Both computational levels here employed yield three minima, in which the C2NNO frame is ‘planar’ or ‘quasi-planar’. Important correlations between NBO charges and geometric parameters, as well as between some structural features and dipole moments are also discussed. A total of 17 structures have been found for the (C2H5)2N-N=O molecule. Two ranges of values have been obtained for the dipole moment, with the largest values occurring for the structures in which the nitrogen lone pair is parallel to the NO group π system. For instance, these two ranges are from ~4.1 to 4.5 D, and from ~1.6 to 2.1 D, at the MP2/cc-pVTZ level. These ranges are consistent with a larger and a smaller contribution of a dipolar resonance structure, respectively. As the method or basis set changes the values of the dipole moments change by at most ~0.23 D. FigureN-nitrosodiethylamine

CASSCF and multireference CI with singles and doubles study of low-lying valence and Rydberg states of 2H-tetrazole.

Complete active space self‐consistent field (CASSCF) and multireference CI with singles and doubles (MR‐CISD) calculations [including extensivity corrections, at MR‐CISD+Q and multireference averaged quadratic coupled cluster (MR‐AQCC) levels] have been performed to characterize the low‐lying valence and the Rydberg states of 2H‐tetrazole. The highest level results (MR‐AQCC/d′‐aug′‐cc‐pVDZ) indicate the following ordering of the valence singlet excited states: S1 (n–π*), 6.06 eV; S2 (n–π*), 6.55 eV; S3 (π–π*), 6.55 eV. The MR‐CISD+Q/d′‐aug′‐cc‐pVDZ results indicate the same ordering, but at slight higher energies: 6.16, 6.68, and 6.69 eV, respectively. According to our MR‐CISD+Q/d′‐aug′‐cc‐pVDZ results, the next two states are Rydberg states, at 7.69 eV (π–3s) and 7.89 eV (n–3s). The calculated energies of these two states, as well as their proximity, are consistent with the conclusion reached by Palmer and Beveridge (Chem Phys 1987, 111, 249) that the first band of the photoelectron spectrum of 2H‐tetrazole is likely to be associated to the first two ionizations processes (of π and N lone pair electrons), at energies close to 11.3 eV.

Challenges encountered during development of Mn porphyrin-based, potent redox-active drug and superoxide dismutase mimic, MnTnBuOE-2-PyP5 +, and its alkoxyalkyl analogues

We disclose here the studies that preceded and guided the preparation of the metal-based, redox-active therapeutic Mn(III) meso-tetrakis(N-n-butoxyethylpyridyl)porphyrin, MnTnBuOE-2-PyP5+ (BMX-001), which is currently in Phase I/II Clinical Trials at Duke University (USA) as a radioprotector of normal tissues in cancer patients. N-substituted pyridylporphyrins are ligands for Mn(III) complexes that are among the most potent superoxide dismutase mimics thus far synthesized. To advance their design, thereby improving their physical and chemical properties and bioavailability/toxicity profiles, we undertook a systematic study on placing oxygen atoms into N-alkylpyridyl chains via alkoxyalkylation reaction. For the first time we show here the unforeseen structural rearrangement that happens during the alkoxyalkylation reaction by the corresponding tosylates. Comprehensive experimental and computational approaches were employed to solve the rearrangement mechanism involved in quaternization of pyridyl nitrogens, which, instead of a single product, led to a variety of mixed N-alkoxyalkylated and N-alkylated pyridylporphyrins. The rearrangement mechanism involves the formation of an intermediate alkyl oxonium cation in a chain-length-dependent manner, which subsequently drives differential kinetics and thermodynamics of competing N-alkoxyalkylation versus in situ N-alkylation. The use of alkoxyalkyl tosylates, of different length of alkyl fragments adjacent to oxygen atom, allowed us to identify the set of alkyl fragments that would result in the synthesis of a single compound of high purity and excellent therapeutic potential.

Spin-Forbidden Branching in the Mechanism of the Intrinsic Haber-Weiss Reaction

Abstract The mechanism of the O2 ⋅− and H2O2 reaction (Haber–Weiss) under solvent‐free conditions has been characterized at the DFT and CCSD(T) level of theory to account for the ease of this reaction in the gas phase and the formation of two different set of products (Blanksby et al., Angew. Chem. Int. Ed. 2007, 46, 4948). The reaction is shown to proceed through an electron‐transfer process from the superoxide anion to hydrogen peroxide, along two pathways. While the O3 ⋅− + H2O products are formed from a spin‐allowed reaction (on the doublet surface), the preferred products, O⋅−(H2O)+3O2, are formed through a spin‐forbidden reaction as a result of a favorable crossing point between the doublet and quartet surface. Plausible reasons for the preference toward the latter set are given in terms of the characteristics of the minimum energy crossing point (MECP) and the stability of an intermediate formed (after the MECP) in the quartet surface. These unique results show that these two pathways are associated with a bifurcation, yielding spin‐dependent products.

UV-photoexcitation and ultrafast dynamics of HCFC-132b (CF2ClCH2Cl)

The UV‐induced photochemistry of HCFC‐132b (CF2ClCH2Cl) was investigated by computing excited‐state properties with time‐dependent density functional theory (TDDFT), multiconfigurational second‐order perturbation theory (CASPT2), and coupled cluster with singles, doubles, and perturbative triples (CCSD(T)). Excited states calculated with TDDFT show good agreement with CASPT2 and CCSD(T) results, correctly predicting the main excited‐states properties. Simulations of ultrafast nonadiabatic dynamics in the gas phase were performed, taking into account 25 electronic states at TDDFT level starting in two different spectral windows (8.5 ± 0.25 and 10.0 ± 0.25 eV). Experimental data measured at 123.6 nm (10 eV) is in very good agreement with our simulations. The excited‐state lifetimes are 106 and 191 fs for the 8.5 and 10.0 eV spectral windows, respectively. Internal conversion to the ground state occurred through several different reaction pathways with different products, where 2Cl, C‐Cl bond breakage, and HCl are the main photochemical pathways in the low‐excitation region, representing 95% of all processes. On the other hand, HCl, HF, and C‐Cl bond breakage are the main reaction pathways in the higher excitation region, with 77% of the total yield.

Effect of methylation on relative energies of tautomers and on the intramolecular proton transfer barriers of protonated nitrosamine: A MR-CISD study

MR‐CISD, MR‐CISD+Q, and MR‐AQCC calculations have been performed on the minima and transition states (corresponding to intramolecular proton transfer between the protonation sites) of the ground state of protonated nitrosamine and N,N‐dimethylnitrosamine. Our highest level results (MR‐AQCC/cc‐pVTZ) for the smaller system indicate that protonation on the N amino (2a) is practically as favorable as the most favorable protonation on the O atom (1a). They also suggest that protonation on the nitroso N atom (2c) is ∼14.5 kcal/mol less favorable than 1a. Results obtained at the MR‐CISD+Q/cc‐pVTZ level indicate that the effect of methylation on the relative energies of the tautomers is, in order of importance, 2a > 2c and increases their energies by ∼17.5 and 4.8 kcal/mol, respectively. They also indicate that methylation alters significantly the intramolecular proton transfer barriers. The largest differences between the common geometric parameters of both systems have been found for 2a.

Valence and Rydberg states of CH3Cl: a MR-CISD study

In this work ten singlet and nine triplet states are studied through multi-reference configuration interactions with singles and doubles (MR-CISD), including Davidson extensivity correction (MR-CISD+Q). For the first time the excited states whose energies are larger than ∼9.5 eV have been calculated using highly correlated methods. The energies, spatial extent (〈r2〉), configurations weights and oscillator strengths (f) have been computed. At the MR-CISD+Q level the excited states energies vary from ∼7.51 to 11.98 eV. The lowest (nσ*) excited singlet state is significantly mixed with the n3pa1 and n3s Rydberg states, while the next (n3s) has a non-negligible mixture with the nσ* state. The next three singlet states obtained result from the (nCl)3(3pe)1 configuration and are almost degenerate. The next (n3pa1) singlet state is significantly mixed with the nσ* state, while the last three have σC–Cl → Rydberg (3s or 3p) as the main configurations. According to the f values the most intense transition is to the 41A1 state, a σ3pa1 Rydberg state mixed with the σσ* and σ3s configurations. Our results indicate that the σσ* configuration is responsible for the high f value of the gs → 41A1 transition. The Rydberg-valence mixing is greatly reduced in the triplet states whose singlet counterparts have significant multiconfigurational character. The 23A1 state (σσ*) does not have its singlet counterpart, while the 41A1 state (σ3pa1 + σσ* + σ3s) does not have its triplet counterpart. The obtained results are in good agreement with experimental results and with previous CASPT2 results.