Pyridinium Ylide-Mediated Diastereoselective Synthesis of Spirocyclopropanyl-pyrazolones via Cascade Michael/Substitution Reaction.

We have devised a highly diastereoselective formal [2 + 1] annulation reaction of arylidene/alkylidine-pyrazolones with in situ-generated supported as well as standard pyridinium ylides to construct spirocyclopropanyl-pyrazolones. The cascade approach exhibits a wide range of functional group tolerance, gram-scale capability, and substrate versatility. A diverse range of spirocyclic cyclopropanes was synthesized extensively with both mediators, and the supported pyridine was reused in subsequent cycles. Density functional theory calculations confirmed the formation of spirocyclopropane as the lower energy pathway.

Theoretical Investigation of Bimolecular Carbon Chain Growth Reactions in the Interstellar Media.

Detection of molecular anions in interstellar media implies that negatively charged species play a prominent role in astrochemical reactions. Among the observed species, carbon chain anions are important, as they can be precursors for the production of complex organic molecules. These anions can form either via direct electron attachment to the corresponding neutral species or through chain growth reactions of smaller anions, resulting in longer chains. In a recent study, crossed beam experiments coupled with velocity map imaging techniques were used to investigate the carbon chain growth reaction C2n- + C2H2 → C2n+2Hm- + H2-m (n = 1-3, m = 0,1). Products and branching ratios were established from experimental data. In the present work, electronic structure calculations and on-the-fly direct dynamics simulations were used to study these reactions. Energy profiles were investigated by using different density functional methods. Direct trajectory simulations were performed at the experimental collision energies using the B3LYP/6-31+G* level of theory. Trajectory analysis showed a variety of reaction pathways, and detailed atomic-level reaction mechanisms are presented.

NNN manganese complex-catalyzed α-alkylation of methyl ketones using alcohols: an experimental and computational study.

We present here a phosphine-free, quinoline-based pincer Mn catalyst for α-alkylation of methyl ketones using primary alcohols as alkyl surrogates. The C-C bond formation reaction proceeds via a hydrogen auto-transfer methodology. The sole by-product formed is water, rendering the protocol atom efficient. Electronic structure theory studies corroborated the proposed mechanism.

The rapid construction and biological evaluation of densely substituted pyrrolo[1,2-a]indoles via a BF3·OEt2-assisted cascade approach.

Lewis-acid cascade reactions promoted by BF3·OEt2 are reported for the synthesis of highly substituted pyrrolo[1,2-a]indoles and congeners of benzofuro[2,3-b]indoles. These reactions are highly regio- and diastereoselective towards generating up to five contiguous stereogenic centers, including two vicinal quaternary centers. Furthermore, an established cascade approach and the mechanism proposed herein are well supported by quantum chemistry calculations. In addition, a self-dimerization intermediate was trapped and isolated to establish a strategy for potential access to both pyrrolo and benzo indole derivatives, leaving sufficient freedom for broadening. Furthermore, in-silico molecular docking and all atomistic molecular dynamic (MD) simulation analysis suggests that the synthesized pyrrolo[1,2-a]indole derivatives stably bind at the active site of the mycobacterial secreted tyrosine phosphatase B (MptpB) enzyme, an emerging anti-mycobacterial drug target. Deep learning-based affinity predictions and MMPBGBSA-based energy calculations of the docked poses are presented herein.

Reusable Supported Pyridine-Mediated Cascade Synthesis of trans-2,3-Dihydroindoles via In Situ-Generated N-Ylide.

Merrifield resin-anchored pyridines were prepared and applied as reusable mediators for trans-selective cascade synthesis of 2,3-dihydroindoles. The developed approach relied on in situ N-ylide formation followed by Michael substitution reactions. The cascade reaction was also carried out efficiently with simple pyridine. The products were further transformed into synthetically valuable compounds, and supported pyridine was reused for multiple cycles. Density functional theory calculations confirmed the trans-selectivity as the lower-energy pathway.

Direct chemical dynamics simulations of CN- + CH3I bimolecular nucleophilic substitution reaction.

Bimolecular nucleophilic substitution reactions have been studied for more than a century. Experimental and theoretical investigations of these reactions are extensively going on due to their wide applicability and the discovery of new features of these reactions. The CN- + CH3I nucleophilic substitution reaction can result in two isomeric products (NCCH3/CNCH3 + I-) because the incoming nucleophile has two reactive centers. Velocity map imaging experiments of this reaction have been reported and dominant direct rebound dynamics and high internal energy excitation of the reaction products were found in the experiments. However, it was not possible to directly obtain the isomer branching ratios from the experimental data and statistical ratios were predicted based on a numerical simulation. In the present work, direct chemical dynamics simulations of this reaction were performed using density functional theory and semi-empirical potential energy surfaces. Reactivity was low at all collision energies and direct rebound dynamics was observed in a major fraction of trajectories in agreement with experiments. However, the branching ratios computed from the trajectories were different from the previously reported estimates. Product energy distributions and scattering angles were computed and detailed atomic level reaction mechanisms are presented.

Investigations of Vacancy-Assisted Selective Detection of NO2 Molecules in Vertically Aligned SnS2.

Two important methods for enhancing gas sensing performance are vacancy/defect and interlayer engineering. Tin sulfide (SnS2) has recently attracted much attention for sensing of the NO2 gas due to its active surface sites and tunable electronic structure. Herein, SnS2 has been synthesized by the chemical vapor deposition (CVD) method followed by nitrogen plasma treatment with different exposure times for fast detection of NO2 molecules. Plasma treatment created a substantial number of surface vacancies on SnS2 flakes, which were controlled by the exposure period to modify the surface of flakes. After 12 min of nitrogen plasma treatment, SnS2 nanoflakes show considerable improvement in NO2 sensing characteristics, including a high sensing response of ∼264% toward 100 ppm NO2 at 120°C. The enhancement in the relative response of the sensor is due to the electronic interaction between NO2 molecules and the S vacancies on the surface of SnS2. Density functional theory (DFT) computations indicate that the S-vacancy defects on the surface dominate the effective NO2 detection and the NO2 adsorption mechanism transition from physisorption to chemisorption. Adsorption kinetics of the NO2 gas over SnS2 nanoflake-based chemiresistor sensors were studied using the Lee and Strano model [ Langmuir 2005, 21(11), 5192-5196]. The irreversible rate of the reaction for various NO2 concentrations exposed to the gas sensor is extracted using this model, which also appropriately describes the response curves. The forward rate constant of the irreversible gas sensor increased with the increase of the N2 plasma treatment time and reached the maximum in the 12 min plasma-treated sample. Through defect engineering, this research may open up new vistas for the design and synthesis of 2D materials with enhanced sensing properties.

Collision Induced Dissociation of Deprotonated Isoxazole and 3-Methyl Isoxazole via Direct Chemical Dynamics Simulations.

Isoxazoles are an important class of organic compounds widely employed in synthesis and drug design. Fragmentation chemistry of the parent isoxazole molecule and its substituents has been the subject of several experimental and theoretical investigations. Collision induced dissociation (CID) of isoxazole and its substituents has been studied experimentally under negative ion conditions. Based on the observed reaction products, dissociation patterns were proposed. In the present work, we studied the dissociation chemistry of deprotonated isoxazole and 3-methyl isoxazole using electronic structure theory calculations and direct chemical dynamics simulations. Various deprotonated isomers of these molecules were activated by collision with an Ar atom, and the ensuing fractionation patterns were studied using on-the-fly classical trajectory simulations at the density functional B3LYP/6-31+G* level of electronic structure theory. A variety of reaction products and pathways were observed, and it was found that a nonstatistical shattering mechanism dominates the CID dynamics of these molecules. Simulation results are compared with experiments, and detailed atomic level dissociation mechanisms are presented.

E-Z Isomerization in Guanidine: Second-order Saddle Dynamics, Non-statisticality, and Time-frequency Analysis.

Our recent work on the E-Z isomerization reaction of guanidine using ab initio chemical dynamics simulations [Rashmi et al., Regul. Chaotic Dyn. 2021, 26, 119] emphasized the role of second-order saddle (SOS) in the isomerization reaction; however, we could not unequivocally establish the non-statistical nature of the dynamics followed in the reaction. In the present study, we performed thousands of on-the-fly trajectories using forces computed at the MNDO level to investigate the influence of second-order saddle in the E-Z isomerization reaction of guanidine and the role of intramolecular vibrational energy redistribution (IVR) on the reaction dynamics. The simulations reveal that while majority of the trajectories follow the traditional transition state pathways, 15 % of the trajectories follow the SOS path. The dynamics was found to be highly non-statistical with the survival probabilities of the reactants showing large deviations from those obtained within the RRKM assumptions. In addition, a detailed analysis of the dynamics using time-dependent frequencies and the frequency ratio spaces reveal the existence of multiple resonance junctions that indicate the existence of regular dynamics and long-lived quasi-periodic trajectories in the phase space associated with non-RRKM behavior.

Theoretical Investigation of Dissociation versus Intramolecular Rearrangements in Aminohydroxymethylene.

Aminohydroxymethylene (H2N-C̈-OH) is the simplest aminooxycarbene which is a heteroatom stabilized carbene. This highly reactive molecule was prepared in an Ar matrix in a recent experimental work. Unimolecular reactivity of this astrochemically important molecule was investigated and only fragmentations were identified contrary to the observations of both fragmentations and intramolecular rearrangements in other hydroxycarbenes. These rearrangement reactions form the corresponding imine and carbonyl compounds. In the present work, direct chemical dynamics simulations of unimolecular chemistry of aminohydroxymethylene were performed in the gas phase to study atomic level dissociation mechanisms. Classical trajectories were generated on-the-fly using potentials and gradients computed at the density functional B3LYP/6-31+G* level of electronic structure theory. Simulation results showed that intramolecular rearrangements accompany fragmentations during the unimolecular decay process of aminohydroxymethylene. However, the average lifetime of the intermediate isomers were found to be only few picoseconds which might not have been long enough for detection in the experiments.

Unimolecular Dissociation of γ-Ketohydroperoxide via Direct Chemical Dynamics Simulations.

γ-Ketohydroperoxide [3-(hydroperoxy)propanal] is an important reagent in synthetic chemistry and, in particular, oxidation reactions. It is considered to be a precursor for secondary organic aerosol formation in the troposphere. Due to enhanced reactivity and limitations associated with analytical techniques, theoretical methods have been employed to study the unimolecular reactivity of hydroperoxides. A number of automated reaction discovery techniques have been used to study the reactivity of γ-ketohydroperoxide, and a large number of reactions have been reported in such studies. In the present work, we have investigated the unimolecular reaction dynamics of this molecule using electronic structure theory calculations and direct chemical dynamics simulations to assess the relevance of different reaction pathways. Classical trajectories were launched from the reactant well with fixed amounts of total energies and integrated on-the-fly using density functional B3LYP/6-31+G* model chemistry. Three dissociation channels among the previously reported reactions were identified as important. Korcek decomposition, which was proposed earlier as a source of carbonyl compounds from thermal decomposition of γ-ketohydroperoxide, was not observed in the present high-temperature simulations. However, trajectories showed the formation of carbonyl compounds such as aldehydes via other pathways. Results are compared with previous studies, and detailed atomic-level reaction mechanisms are presented.

Theoretical investigation of the dissociation chemistry of formyl halides in the gas phase.

Halogen substituted analogues of formaldehyde, HXCO (X = F, Cl, Br, and I), play a crucial role in the degradation of stratospheric ozone. Several spectroscopic and quantum chemistry investigations of the dissociation chemistry of formyl halides have been reported in the literature. Due to their importance in combustion and atmospheric chemistry, we investigated the gas phase dissociation of formyl halides using electronic structure theory, direct chemical dynamics simulations, and Rice-Ramsperger-Kassel-Marcus rate constant calculations. Chemical dynamics simulations were performed using density functional B3LYP/6-31G* theory with suitable effective core potentials for the halogen atoms. Simulations showed multiple pathways and mechanisms for the dissociation of formyl halides. The major reaction products were HX + CO which formed via direct and indirect pathways. Trajectory lifetime distribution calculations indicated non-statistical dissociation dynamics.

Chemical Dynamics Simulations of Curtius Reaction of Acetyl- and Fluorocarbonyl Azides.

Curtius rearrangement is the elimination of N2 from carbonyl azides RC(O)N3 to form isocyanates RNCO. Two mechanisms, viz., stepwise and concerted have been proposed in the literature for this reaction. The stepwise mechanism involves the formation of a nitrene RC(O)N by elimination of N2 followed by an intramolecular rearrangement of the nitrene to form the isocyanate. The concerted mechanism is a single-step pathway forming the N2 + RNCO products directly. Previous experimental and theoretical studies have indicated that the mechanism is usually concerted for thermal reactions and both stepwise and concerted are preferred under photochemical conditions. In the present work, we investigated the mechanism of Curtius rearrangement of two carbonyl azides with different substituents (R = CH3 and F). Atomic level reaction mechanisms were studied using chemical dynamics simulations under thermal reaction conditions. Classical trajectories were generated on-the-fly at the density functional B3LYP/6-31+G* level of electronic structure theory with similar initial conditions for both the molecules. Simulation results showed a dominant concerted mechanism for CH3C(O)N3 and the operation of both the mechanisms for FC(O)N3. The fluorocarbonyl nitrene FC(O)N had an appreciable lifetime before undergoing intramolecular rearrangement to form the isocyanate. In a small number of trajectories, the product isocyanate produced via the concerted dissociation of FC(O)N3, isomerized back to the nitrene form.

Competing Molecular and Radical Pathways in the Dissociation of Halons via Direct Chemical Dynamics Simulations.

A great deal of attention has been given to the decomposition chemistry of halons (halomethanes) due to their role in stratospheric ozone depletion. Knowledge of certain aspects of dissociation of halons such as the competition between radical and molecular pathways and their mechanistic details is limited. Halon molecules can isomerize to an iso form containing a halogen-halogen bond and such iso-halon forms have been identified as intermediates in condensed phase chemistry. Recently, a quantum chemistry study of role of iso-halons in the gas phase decomposition of halomethanes has been reported. In the present work, we have investigated the ground state dissociation chemistry of select halon molecules - CF2Cl2, CF2Br2, CHBr3, and CH2BrCl using electronic structure theory calculations and direct chemical dynamics simulations. Classical trajectories were generated on-the-fly using density functional PBE0/6-31G* level of theory at a fixed total energy. Simulation results showed that molecular products, in general, were dominant for all the four molecules at the chosen energy. A variety of mechanisms such as direct dissociation via multicenter transition states, decomposition via isomerization, radical recombinations, and roaming pathways contributed to the formation of molecular products. Atomic level mechanisms are presented, and the role of iso-halons in the gas phase chemistry of halomethanes is clearly established.

Star-Shaped ESIPT-Active Mechanoresponsive Luminescent AIEgen and Its On-Off-On Emissive Response to Cu2+/S2.

Design and development of multifunctional materials have drawn incredible attraction in recent years. Herein, we report the design and construction of versatile star-shaped intramolecular charge transfer (ICT)-coupled excited-state intramolecular proton transfer (ESIPT)-active mechanoresponsive and aggregation-induced emissive (AIE) luminogen triaminoguanidine-diethylaminophenol (LH3 ) conjugate from simple precursors triaminoguanidine hydrochloride and 4-(N,N-diethylamino)salicylaldehyde. Solvent-dependent dual emission in nonpolar to polar protic solvents implies the presence of ICT-coupled ESIPT features in the excited state. Aggregation-enhanced emissive feature of LH3 was established in the CH3CN/water mixture. Furthermore, this compound exhibits mechanochromic fluorescence behavior upon external grinding. Fluorescence microscopy images of pristine, crystal, and crushed crystals confirm the naked-eye mechanoresponsive characteristics of LH3 . In addition, LH3 selectively sensed a Cu2+ ion through a colorimetric and fluorescence "turn-off" route, and subsequently, the LH3 -Cu2+ ensemble could act as a selective and sensitive sensor for S2- in a "turn-on" fluorescence manner via a metal displacement approach. Reversible "turn-off-turn-on" features of LH3 with Cu2+/S2- ions were efficiently demonstrated to construct the IMPLICATION logic gate function. The Cu2+/S2--responsive sensing behavior of LH3 was established in the paper strip experiment also, which can easily be characterized by the naked eye under daylight as well as a UV lamp (λ = 365 nm).

Theoretical investigation of the isomerization pathways of diazenes: torsion vs. inversion.

Diazenes are an important family of organic compounds used widely in synthetic and materials chemistry. These molecules have a planar geometry and exhibit cis-trans isomerization. The simplest of all these molecules - diazene (N2H2) - has been subjected to several experimental and theoretical studies. Two mechanisms have been proposed for the cis-trans isomerization of diazene, which are an in-plane inversion and an out-of-plane torsion. The activation energies for these pathways are similar and the competition between these two mechanisms has been discussed in the literature based on electronic structure theory calculations. Three decades ago, a classical dynamics investigation of diazene isomerization was carried out using a model Hamiltonian and it was indicated that the in-plane inversion is forbidden classically because of a centrifugal barrier and the out-of-plane torsion is the only isomerization pathway. In the present work, we investigated the cis-trans isomerization dynamics of diazene using ab initio classical trajectory simulations at the CASSCF(2,2)/aug-cc-pVDZ level of electronic structure theory. The simulation results confirmed the presence of the aforementioned centrifugal barrier for the inversion and torsion was the only observed pathway. The calculations were repeated for a similar system (difluorodiazene, N2F2) and again the centrifugal barrier prevented the inversion pathway.

Direct Chemical Dynamics Simulations of H3+ + CO Bimolecular Reaction.

The proton transfer reaction H3+ + CO → HCO+/HOC+ + H2 has gained considerable attention in the literature due to its importance in interstellar chemistry. The reaction products-formyl cation (HCO+) and isoformyl cation (HOC+)-are known to initiate multiple chemical reaction networks, resulting in complex molecules found in space. Several experimental and theoretical studies probing the structure and energetics of the [H3CO]+ system, HCO+/HOC+ product branching ratios, reaction mechanisms, etc., have been reported in the literature. In the present work, we investigated the H3+ + CO bimolecular reaction in the gas phase using direct dynamics methodology. The simulation conditions were chosen to mimic recently reported velocity map imaging experiments on the same reaction. The calculations were performed using the density functional PBE0/aug-cc-pVDZ level of electronic structure theory. Internal energy and scattering angle distributions of reaction products found from the simulations are in qualitative agreement with the experiment. However, the product branching ratios at low collision energies were in contrast with the experimental predictions. Interesting dynamical features were observed in the simulations, and detailed atomic level mechanisms are presented.

Unimolecular decomposition of formamide via direct chemical dynamics simulations.

Formamide (NH2CHO), being the simplest organic molecule containing an amide functional group, serves as a prototype to study protein and peptide chemistry. Formamide has been found in Comets and interstellar media and its decomposition results in smaller molecules such as NH3, CO, HCN, HNCO, etc. These smaller molecules are considered to have been potential precursors for the formation of complex biological molecules, such as nucleic acids and nucleobases, in the early Earth. Several experimental and theoretical investigations of formamide decomposition have been reported in the literature. In the present work, unimolecular decomposition of formamide in the electronic ground state was investigated by classical direct chemical dynamics simulations. The calculations were performed at three different energies using the density functional B3LYP/aug-cc-pVDZ level of electronic structure theory. The major dissociation products observed were NH3, CO, H2, HNCO, H2O, HCN, and HNC along with products of a few minor dissociation channels. Reactivity, atomic level mechanisms, and product branching ratios were investigated as a function of total energy.

Dissociation Chemistry of 3-Oxetanone in the Gas Phase.

3-Oxetanone is a strained cyclic molecule which plays an important role in synthetic chemistry. A few studies exist in the literature about the equilibrium properties of this molecule and the dissociation patterns of substituted 3-oxetanones. For the unsubstituted 3-oxetanone, formation of ketene (CH2CO) and formaldehyde (HCHO) was considered to be the major dissociation pathway. In a recent work, pyrolysis products of 3-oxetanone molecule in the gas phase were investigated by Fourier transform infrared spectroscopy and photoionization mass spectrometry. In this study, an additional dissociation channel forming ethylene oxide (c-C2H4O) and carbon monoxide CO was reported. In the present work, gas phase dissociation chemistry of 3-oxetanone was investigated by electronic structure theory, ab initio classical chemical dynamics simulations, and Rice-Ramsperger-Kassel-Marcus (RRKM) rate constant calculations. The barrier height for the ethylene oxide channel was found to be much higher than the ketene pathway. The dynamics simulations were performed at three different total energies, viz., 150, 200, and 300 kcal/mol, and multiple reaction pathways and varying branching ratios observed. A new dissociation channel involving a ring-opened isomer of ethylene oxide was identified in the simulations. This pathway has a lower energy barrier and was dominant in our dynamics simulations.

Classical Dynamics Simulations of Dissociation of Protonated Tryptophan in the Gas Phase.

Gas phase decomposition of protonated amino acids are of great interest due to their role in understanding protein and peptide chemistry. Several experimental and theoretical studies have been reported in the literature on this subject. In the present work, decomposition of the aromatic amino acid protonated tryptophan was studied by on-the-fly classical chemical dynamics simulations using density functional theory. Mass spectrometry and electronic structure theory studies have shown multiple dissociation pathways for this biologically relevant molecule. Unlike aliphatic amino acids, protonated tryptophan dissociates via NH3 elimination rather than the usual iminium ion formation by combined removal of H2O and CO molecules. Also, a major fragmentation pathway in the present work involves Cα-Cß bond fission. Results of the chemical dynamics simulations reported here are in overall agreement with experiments, and detailed atomic level mechanisms are presented.