New-generation electron-propagator methods for vertical electron detachment energies of molecular anions: benchmarks and applications to model green-fluorescent-protein chromophores.

Ab initio electron-propagator calculations continue to be useful companions to experimental investigations of electronic structure in molecular anions. A new generation of electron-propagator methods recently has surpassed its antecedents' predictive accuracy and computational efficiency. Interpretive clarity has been conserved, for no adjustable parameters have been introduced in the preparation of molecular orbitals or in the formulation of approximate self-energies. These methods have employed the diagonal self-energy approximation wherein each Dyson orbital equals a canonical Hartree-Fock orbital times the square root of a probability factor. Numerical tests indicate that explicitly renormalized, diagonal self-energies are needed when Dyson orbitals have large valence nitrogen, oxygen or fluorine components. They also demonstrate that even greater accuracy can be realized with generalizations that do not employ the diagonal self-energy approximation in the canonical Hartree-Fock basis. Whereas the diagonal methods have fifth-power arithmetic scaling factors, the non-diagonal generalizations introduce only non-iterative sixth-power contractions. Composite models conserve the accuracy of the most demanding combinations of self-energy approximations and flexible basis sets with drastically reduced computational effort. Composite-model results on anions that resemble the chromophore of the green fluorescent protein illustrate the interpretive capabilities of explicitly renormalized self-energies. Accurate predictions on the lowest vertical electron detachment energy of each anion confirm experimental data and the utility of the diagonal self-energy approximation.

Ab Initio Electron Propagators with an Hermitian, Intermediately Normalized Superoperator Metric Applied to Vertical Electron Affinities.

New-generation ab initio electron propagator methods for calculating electron detachment energies of closed-shell molecules and anions have surpassed their predecessors' accuracy and computational efficiency. Derived from an Hermitian, intermediately normalized superoperator metric, these methods contain no adjustable parameters. To assess their versatility, a standard set (NIST-50-EA) of 50 vertical electron affinities of small closed-shell molecules based on NIST reference data has been created. Errors with respect to reference data on 23 large, conjugated organic photovoltaic (OPV23) molecules have also been analyzed. All final states are valence anions that correspond to electron affinities between 0.2 and 4.2 eV. For a given scaling of the arithmetic bottleneck, the new-generation methods obtain the lowest mean absolute errors (MAEs). The best methods with fifth-power arithmetic scaling realize MAEs below 0.1 eV. Composite models comprising cubically and quintically scaling calculations executed with large and small basis sets, respectively, produce OPV23 MAEs near 0.05 eV. The accuracy of quintically scaling methods executed with large basis sets is thereby procured with reduced computational effort. New-generation results obtained with and without the diagonal self-energy approximation in the canonical Hartree-Fock basis have been compared. These results indicate that Dyson orbitals closely resemble canonical Hartree-Fock orbitals multiplied by the square root of a probability factor above 0.85.

New-Generation Electron-Propagator Methods for Molecular Electron-Binding Energies.

A new generation of electron-propagator methods for the calculation of electron binding energies has surpassed its antecedents with respect to accuracy, efficiency, and interpretability. No adjustable parameters are introduced in these fully ab initio procedures. Numerical tests versus several databases of valence, vertical electron binding energies of closed-shell molecules and atoms have been performed. Easily interpreted self-energy approximations with cubic arithmetic scaling produce mean absolute errors (MAEs) of 0.2 and 0.3 eV for electron detachments and attachments, respectively. The most accurate explicitly renormalized methods with fifth-power arithmetic scaling yield MAEs below 0.1 eV for detachments and attachments. Approximate renormalization leads to more efficient fifth-power alternatives for electron detachments that achieve similar accuracy with fewer bottleneck operations. Composite protocols generate excellent predictions versus highly accurate basis-extrapolated standards and experiments. The validity of the diagonal self-energy approximation and the accuracy of the approximate renormalizations are confirmed. The success of these perturbative methods based on canonical Hartree-Fock orbitals rests on a Hermitized, intermediately normalized superoperator metric. The results of all of the new-generation calculations may be analyzed in terms of final-state orbital relaxation and differential correlation effects.

Electron Propagator Theory of Vertical Electron Detachment Energies of Anions: Benchmarks and Applications to Nucleotides.

A new generation of ab initio electron-propagator self-energy approximations that are free of adjustable parameters is tested on a benchmark set of 55 vertical electron detachment energies of closed-shell anions. Comparisons with older self-energy approximations indicate that several new methods that make the diagonal self-energy approximation in the canonical Hartree-Fock orbital basis provide superior accuracy and computational efficiency. These methods and their acronyms, mean absolute errors (in eV), and arithmetic bottlenecks expressed in terms of occupied (O) and virtual (V) orbitals are the opposite-spin, non-Dyson, diagonal second-order method (os-nD-D2, 0.2, OV2), the approximately renormalized quasiparticle third-order method (Q3+, 0.15, O2V3) and the approximately renormalized, non-Dyson, linear, third-order method (nD-L3+, 0.1, OV4). The Brueckner doubles with triple field operators (BD-T1) nondiagonal electron-propagator method provides such close agreement with coupled-cluster single, double, and perturbative triple replacement total energy differences that it may be used as an alternative means of obtaining standard data. The new methods with diagonal self-energy matrices are the foundation of a composite procedure for estimating basis-set effects. This model produces accurate predictions and clear interpretations based on Dyson orbitals for the photoelectron spectra of the nucleotides found in DNA.

A new generation of non-diagonal, renormalized self-energies for calculation of electron removal energies.

A new generation of diagonal self-energies for the calculation of electron removal energies of molecules and molecular ions that has superseded its predecessors with respect to accuracy, efficiency, and interpretability is extended to include non-diagonal self-energies that permit Dyson orbitals to be expressed as linear combinations of canonical Hartree-Fock orbitals. In addition, an improved algorithm for renormalized methods eliminates the convergence difficulties encountered in the first studies of the new, diagonal self-energies. A dataset of outer-valence, vertical ionization energies with almost full-configuration-interaction quality serves as a standard of comparison in numerical tests. The new non-diagonal, renormalized methods are slightly more accurate than their diagonal counterparts, with mean absolute errors between 0.10 and 0.06 eV for outer-valence final states. This advantage is procured at the cost of an increase in the scaling of arithmetic bottlenecks that accompany the inclusion of non-diagonal self-energy terms. The new, non-diagonal, renormalized self-energies are also more accurate and efficient than their non-diagonal predecessors.

Examining the level of public awareness on the Sustainable Development Goals in Africa: An empirical evidence from Ghana.

Nations which are part of the United Nations are required to institute appropriate measures to fulfil the vision of the Sustainable Development Goals (SDGs). However, for this to be possible, all stakeholders including the general public need to be fully aware of the SDGs. This research examined the level of public awareness about the SDGs among Ghanaians based on the views of 431 respondents. Means, standard deviation, Mann-Whitney U test, Kruskal Wallis and Pearson Product-Moment Correlations were used for data analysis. The study found that awareness level on SDG 1 (ending poverty), SDG 2 (zero hunger, food security, nutrition and sustainable agriculture), SDG 3 (health and well-being), SDG 5 (gender equality), and SDG 6 (clean water and sanitation) was high among Ghanaians. However, awareness level on SDG 9 (industry, innovation and infrastructure), SDG 14 (conservation of life below water), and SDG 16 (peace, justice and strong institutions) was very low among Ghanaians. No significant difference manifested in the level of awareness among male and female Ghanaians. There were statistically significant differences in educational levels of respondents and their overall level of awareness of the SDGs. Also, there was a low, negative correlation between overall level of awareness and the effectiveness of the communication strategies used in creating awareness about the SDGs. Government should re-examine its communication strategies on the SDGs and put in place a more effective communication policy framework which involves grassroots populations and local communities.

Double Rydberg anions, Rydberg radicals and micro-solvated cations with ammonium-water kernels.

Highly accurate ab initio electron-propagator and coupled-cluster methods are employed to predict the vertical electron attachment energies (VEAEs) of NH4+(H2O)n (n = 1-4) cationic clusters. The VEAEs decrease with increasing n and the corresponding Dyson orbitals are diffused over peripheral, non-hydrogen bonded protons. Clusters formed from NH4- double Rydberg anions (DRAs) and stabilized by hydrogen bonding or electrostatic interactions are studied through calculations on NH4-(H2O)n complexes and are compared with more stable H-(NH3)(H2O)n isomers. Structures that have cationic and anionic congeners have notable changes in geometry. For all values of n, the hydride-molecule complex H-(NH3)(H2O)n is always the most stable, with large vertical electron detachment energies (VEDEs). NH4-(H2O)n DRA isomers are predicted to have VEDEs that correspond to energetically well-separated peaks in an anion photoelectron spectrum. Less stable DRA isomers display proton donation from the tetrahedral NH4- fragment to water molecules and VEDEs close to those of previously discovered DRAs. The most stable DRA isomers feature tetrahedral NH4- fragments without H bridges to water molecules and VEDEs that increase with n. Dyson orbitals of NH4-(H2O)n DRAs occupy regions beyond the exterior non-bridging O-H and N-H bonds. Thus, the Rydberg electrons in the uncharged Rydberg radicals and DRAs are held near the outer protons of the water and ammonia molecules. Several bound low-lying excited states of the doublet Rydberg radicals have single electrons occupying delocalized Dyson orbitals of s-like, p-like, d-like, or f-like nodal patterns with the following Aufbau principle: 1s, 1p, 1d, 2s, 2p, 1f.

Electron binding energies and Dyson orbitals of OnH2n+1 +,0,- clusters: Double Rydberg anions, Rydberg radicals, and micro-solvated hydronium cations.

Ab initio electron propagator methods are employed to predict the vertical electron attachment energies (VEAEs) of OH3 +(H2O)n clusters. The VEAEs decrease with increasing n, and the corresponding Dyson orbitals are diffused over exterior, non-hydrogen bonded protons. Clusters formed from OH3 - double Rydberg anions (DRAs) and stabilized by hydrogen bonding or electrostatic interactions between ions and polar molecules are studied through calculations on OH3 -(H2O)n complexes and are compared with more stable H-(H2O)n+1 isomers. Remarkable changes in the geometry of the anionic hydronium-water clusters with respect to their cationic counterparts occur. Rydberg electrons in the uncharged and anionic clusters are held near the exterior protons of the water network. For all values of n, the anion-water complex H-(H2O)n+1 is always the most stable, with large vertical electron detachment energies (VEDEs). OH3 -(H2O)n DRA isomers have well separated VEDEs and may be visible in anion photoelectron spectra. Corresponding Dyson orbitals occupy regions beyond the peripheral O-H bonds and differ significantly from those obtained for the VEAEs of the cations.

A new generation of diagonal self-energies for the calculation of electron removal energies.

A new generation of diagonal self-energy approximations in ab initio electron propagator theory for the calculation of electron removal energies of molecules and molecular ions has been derived from an intermediately normalized, Hermitized super-operator metric. These methods and widely used antecedents such as the outer valence Green's function and the approximately renormalized partial third order method are tested with respect to a dataset of vertical ionization energies generated with a valence, triple-ζ, correlation-consistent basis set and a converged series of many-body calculations whose accuracy approaches that of full configuration interaction. Several modifications of the diagonal second-order self-energy, a version of G0W0 theory based on Tamm-Dancoff excitations and several non-diagonal self-energies are also included in the tests. All new methods employ canonical Hartree-Fock orbitals. No adjustable or empirical parameters appear. A hierarchy of methods with optimal accuracy for a given level of computational efficiency is established. Several widely used diagonal self-energy methods are rendered obsolete by the new hierarchy whose members, in order of increasing accuracy, are (1) the opposite-spin non-Dyson diagonal second-order or os-nD-D2, (2) the approximately renormalized third-order quasiparticle or Q3+, (3) the renormalized third-order quasiparticle or RQ3, (4) the approximately renormalized linear third-order or L3+, and (5) the renormalized linear third-order or RL3 self-energies.

Evidence-based training and mentorship combined with enhanced outcomes surveillance to address the leading causes of neonatal mortality at the district hospital level in Ghana.

OBJECTIVE: To evaluate the impact of a district hospital intervention focused on enhancing healthcare provider capacity to address leading causes of neonatal death: birth asphyxia, infection and prematurity. METHODS: The neonatal quality improvement initiative was launched at two intervention referral district hospitals in Ghana. Local Health and Demographic Surveillance Systems were enlisted to enhance recording of neonatal and infant deaths in the community and at the facility. After baseline site assessments, a team of local paediatric experts conducted three clinical trainings on-site at each intervention hospital. Assessments were conducted to evaluate participant knowledge before and after participation in training modules. Monthly mentorship visits provided additional training to support the adoption of essential early neonatal care practices. RESULTS: In the first year of implementation, the initiative provided focused clinical training to 278 participants. A comparison of pre- and post-training test results demonstrates significant improvement in provider knowledge (73% vs. 89% correct, P < 0.001), with even greater improvement among trainees receiving recurrent refresher training (86% vs. 94% correct, P < 0.001). Participant feedback following training revealed enthusiasm about the programme and improved confidence. CONCLUSIONS: Locally led initiatives that invest directly in healthcare provider education and health systems strengthening represent a promising avenue for reducing neonatal morbidity and mortality. The NQI initiative demonstrates the positive impact of a district hospital intervention that combines on-site training, mentorship and enhanced demographic surveillance.

New-Generation Electron-Propagator Methods for Calculations of Electron Affinities and Ionization Energies: Tests on Organic Photovoltaic Molecules.

A new generation of ab initio electron-propagator self-energies recently superseded its antecedents' accuracy and computational efficiency in calculating vertical ionization energies (VIEs) of closed-shell molecules. (See J. Chem. Phys. 2021, 155, 204107, J. Chem. Theory Comput. 2022, 18, 4927, J. Chem. Phys. 2023, 159, 124109.) No adjustable parameters were introduced in the generation of reference orbitals or in the construction of self-energies. The same approach has been extended in this work to vertical electron affinities (VEAs). Calculations were performed on 24 conjugated, organic photovoltaic molecules with diverse functional groups. These molecules are considerably larger than those studied in previous tests on VIEs. Several new-generation self-energies produce mean absolute errors (MAEs) below 0.1 eV versus ΔCCSD(T) (i.e., total energy differences from the coupled-cluster singles, doubles, and perturbative triples method) VIEs and VEAs obtained with identical basis sets. A composite model employs cubically and quintically scaling algorithms and power-law basis-set extrapolations based on augmented double-triple or triple-quadruple ζ data. Its MAEs are near 0.05 eV versus benchmark values, with 0.03 eV error bars for the lowest VIE and the highest VEA of each molecule. A more efficient and equally accurate composite model for calculating VIEs avoids full transformations of electron repulsion integrals to the molecular orbital basis. High probability factors support the diagonal self-energy approximation, wherein Dyson orbitals are proportional to canonical, Hartree-Fock orbitals.

Using community health workers in community-based growth promotion: what stakeholders think.

The Nutrition and Malaria Control for Child Survival Project is a community-based growth promotion project that utilizes Community Health Workers (CHWs), referred to as Community Child Growth Promoters (CCGPs), as the principal change agents. The purpose of this study was to identify perceptions of key stakeholders about the project and the role of the CCGPs. The study employed qualitative methods: focus group discussions with CCGPs and care givers, exit interviews with care givers, and key informant interviews with health workers and CCGPs. All stakeholders interviewed expressed appreciation for the project and the role of the CCGPs. Respondents indicated that the project, through the CCGPs, had improved access to growth promotion services for children in their communities and made community mobilization for health programs easier. Caregivers appreciated the role of the CCGPS because they were their own people, who spoke their language, understood their situations better, treated them better and were readily accessible. CCGPs on their part believed they were playing a very important role in their communities and were happy with their prestigious position; though they hoped for incentives. This appraisal adds to the evidence on the important role played by CHWs in the developing world.

Mechanistic elucidation of the tandem Diels-Alder/(3 + 2) cycloadditions in the design and syntheses of heterosteroids.

The potential of azasteroids as novel drug candidates has prompted numerous studies towards the syntheses of heterosteroidal skeletons. The preparation of novel azasteroidal compounds and the modification of substituents on their steroidal skeletons might provide excellent congeners with useful biological properties. We present herein computational investigations on the Diels-Alder/(3 + 2) tandem sequential cycloaddition reaction of 21 distinctive derivatives of furylcinnamate with phenyl azides. First, we performed the computational study on the originally reported reaction of ester-substituted furylcinnamate derivatives 1a2 and 1b2 with phenyl azide (3) under the experimental conditions. We extended the scope of these tandem cycloaddition reactions by studying several variants of 1a1, 1b1, and 1c1 and their reactivity towards 3. In all instances of tandem reactions considered in this study, the Diels-Alder cycloaddition step is the rate-determining step (rds). Electron-withdrawing substituted 1a1, 1b1, and 1c1 decrease the barrier of the rds while electron-donating substituents substantially increase the barrier of the rds. The parent reaction (1a1) selectively proceeds via transition states T5Exa to give tandem adduct 5Exa, the experimentally observed tandem product. In the case of 1b1 and 1c1, the reaction is competitively favored via T4Ex and T5Ex to give corresponding 4Ex and 5Ex (the experimentally observed tandem adducts). The various substituents studied demonstrate that the tandem adduct obtained is highly dependent on the substituents on the Diels-Alder intermediate. Whereas electron-withdrawing groups substantially decrease the barrier of the rds, the direct opposite is true for electron-donating groups. A plot of electrophilicity indices against activation energies obtains a favorable correlation. We also investigated the unreported reactivity of a furylcinnamate (2-1a2) with several nitrile imines. Such a reaction is found to proceed through a similar mechanism as those seen for the phenyl azide. It is observed that di-substituted nitrile imines react with furylcinnamate (2-1a2) at favorable energetics than phenyl azide. Calculated GEDT values unveil that the non-polar solvent (toluene) will stabilize the non-polar reaction through van der waals interactions.

Electron Propagator Self-Energies versus Improved GW100 Vertical Ionization Energies.

Ab initio electron propagator (EP) methods that are free of adjustable parameters in their self-energy formulae and in the generation of their orbital bases have been applied to the calculation of the lowest vertical ionization energies (VIEs) of the GW100 set. An improved set of standard results accompanied by irreducible representation assignments has been produced indirectly with coupled-cluster singles and doubles plus perturbative triples, i.e., CCSD(T), total energy differences at initial-state geometries reoptimized (in 28 cases) with the largest applicable point groups. The best compromises of accuracy and efficiency belong to a new generation of EP self-energies, several members of which may be derived from an intermediately normalized, Hermitized super-operator metric. The following diagonal self-energy methods are optimal: opposite-spin non-Dyson second order (os-nD-D2), approximately renormalized partial third order (P3+), approximately renormalized quasiparticle third order (Q3+), and non-Dyson approximately renormalized linear third order version B (nD-L3+B). Their mean absolute errors (MAEs) in electron volts and arithmetic scaling factors expressed in terms of occupied (O) and virtual (V) orbital dimensions are, respectively, (0.18, OV2), (0.14, O2V3), (0.15, O2V3), and (0.11, OV4). The 0.06 eV MAE for the non-diagonal, sixth-power (O2V4) Brueckner doubles, triple-field operator (BD-T1) EP method is exceeded by the 0.1 eV MAE with respect to experiments in seventh-power, ΔCCSD(T) calculations and indicates that BD-T1 may serve as a direct, spin-symmetry-conserving alternative in the generation of standard results for VIEs of larger, closed-shell molecules.

Unveiling the molecular mechanisms of the cycloaddition reactions of aryl hetaryl thioketones and C,N-disubstituted nitrilimines.

Many synthetic routes to constructing biologically active heterocyclic compounds are made feasible through the (3 + 2) cycloaddition (32CA) reactions. Due to a large number of possible combinations of several heteroatoms from either the three-atom components (TACs) or the ethylene derivatives, the potential of the 32CA reactions in heterocyclic syntheses is versatile. Herein, the cycloaddition reaction of thiophene-2-carbothialdehyde derivatives and C,N-disubstituted nitrilimines have been studied through density functional theory (DFT) calculations at the B3LYP/6-311G(d,p) level of theory. In the present study, a one-step 32CA and two-step (4 + 3) cycloaddition (43CA) reaction mechanisms involved in TACs reactions and ethylene derivative have been investigated. In all reactions considered, the one-step 32CA cycloaddition is preferred over the two-step 43CA. The TAC chemoselectively adds across the thiocarbonyl group present in the ethylene derivative in a 32CA fashion to form the corresponding cycloadduct. Analysis of the electrophilic [Formula: see text] and nucleophilic [Formula: see text] Parr functions at the various reaction centers in the ethylene derivative show that the TAC adds across the atomic centers with the largest Parr functions, which is in total agreement with the experimental observation. The selectivities observed in the titled reactions are kinetically controlled.

Genome-wide linkage analysis of malaria infection intensity and mild disease.

Although balancing selection with the sickle-cell trait and other red blood cell disorders has emphasized the interaction between malaria and human genetics, no systematic approach has so far been undertaken towards a comprehensive search for human genome variants influencing malaria. By screening 2,551 families in rural Ghana, West Africa, 108 nuclear families were identified who were exposed to hyperendemic malaria transmission and were homozygous wild-type for the established malaria resistance factors of hemoglobin (Hb)S, HbC, alpha(+) thalassemia, and glucose-6-phosphate-dehydrogenase deficiency. Of these families, 392 siblings aged 0.5-11 y were characterized for malaria susceptibility by closely monitoring parasite counts, malaria fever episodes, and anemia over 8 mo. An autosome-wide linkage analysis based on 10,000 single-nucleotide polymorphisms was conducted in 68 selected families including 241 siblings forming 330 sib pairs. Several regions were identified which showed evidence for linkage to the parasitological and clinical phenotypes studied, among them a prominent signal on Chromosome 10p15 obtained with malaria fever episodes (asymptotic z score = 4.37, empirical p-value = 4.0 x 10(-5), locus-specific heritability of 37.7%; 95% confidence interval, 15.7%-59.7%). The identification of genetic variants underlying the linkage signals may reveal as yet unrecognized pathways influencing human resistance to malaria.

Peri-, Chemo-, Regio-, Stereo- and Enantio-Selectivities of 1,3-dipolar cycloaddition reaction of C,N-Disubstituted nitrones with disubstituted 4-methylene-1,3-oxazol-5(4H)- one: A quantum mechanical study.

The peri-, chemo-, regio-, stereo- and enantio-selectivities of 1,3-dipolar cycloaddition reaction of C,N-disubstituted nitrones with disubstituted 4-methylene-1,3-oxazol-5(4H)-one have been studied using density functional theory (DFT) at the M06-2X/6-311G (d,p) level of theory. The 1,3-dipole preferentially adds chemo-selectively across the olefinic bond in a (3 + 2) fashion forming the corresponding spirocycloadduct. The titled reaction occurs with poor enantio- and stereo-selectivities, but a high degree of regio-selectivity is observed for the addition of the 1,3-dipole across the dipolarophile. Electron-withdrawing groups on the dipolarophile significantly reduce the activation barriers while electron-donating groups on the dipolarophile increase the activation barriers. Analysis of the HOMO and LUMO energies of the two reacting species indicates that the 1,3-dipole reacts as a nucleophile while the dipolarophile reacts as the electrophile. Investigation of the electrophilic Parr function (PK+) at the various reaction centers in the dipolarophile indicates that the 1,3-dipole selectively adds across the atomic species with the largest electrophilic Mulliken and NBO atomic spin densities which is in accordance with the energetic trends observed.

The mechanisms of gallium-catalysed skeletal rearrangement of 1,6-enynes - Insights from quantum mechanical computations.

The transition metal-catalysed skeletal reorganization of 1,6-enynes can lead to three types of products - a type I product occurring via the cleavage of the alkene C-C bonds and the migration of the terminal alkene carbon to the terminus of the alkyne; a type II product arising from cleavage of both the double and the triple bonds followed by insertion of the terminal alkene carbon into the alkyne C-C triple bond; and a type III product which is obtained when there is a cleavage of the olefinic bond followed by formation of two new bonds from each carbon to each of the acetylenic carbons. The course of these reactions is highly dependent on the metal catalyst used and type of substitution at the alkene and alkyne moieties of the enyne. In this mechanistic study of the re-organization of 1,6-enynes catalysed by GaCl3, performed at the DFT M06/6-311G(d,p) level of theory, the parent reaction selectively leads to the formation of the type I product through the formation of the open cyclopropane ring. The presence of substituents at the acetylenic moiety governs the preferred position of the metal along the alkyne bond within the pi-complex: with electron-withdrawing groups (EWGs), the metal prefers the terminal carbon while electron-donating groups (EDGs) lead to the metal preferring the internal carbon. EWGs at the alkyne moiety efficiently favour the formation of the type I product. Substituents at the olefin moiety alter the mechanism of the reaction which may favour the selective formation of the type I or III product depending on the type of substituent. EWGs at the olefinic moiety favour formation of the type III product when the alkyne moiety is unsubstituted whiles EDGs forms the type I product selectively. Solvent and temperature have no substantial effects on the energetic trends and product distribution. Hence, gas-phase calculations are deemed adequate for the problem at hand.

Quantum chemical studies on the mechanistic aspects of tandem sequential cycloaddition reactions of cyclooctatetraene with ester and nitrones.

The mechanisms of the tandem sequential [4 + 2]/[3 + 2] and [3 + 2]/[4 + 2] cycloaddition sequences involving an ester, cyclooctatetraene (COTE), and cyclic and acyclic nitrones for the formation of a diverse range of isoxazolidine derivatives and other synthetic precursors are reported. A thorough exploration of the PES has characterized several regio-, stereo- and enantio-selective mechanistic channels involved in these reactions. A perturbation molecular orbital (PMO) analysis been employed to rationalize the results. It has also been found that the initial electrocyclic ring closure of the COTE is the rate-determining step in the tandem sequential [4 + 2]/[3 + 2] addition sequence. The thermolytic breakdown of the tandem adducts to subsequent monocyclic, bicyclic and tricyclic adducts occurs generally with very high activation barriers making it an inconvenient synthetic approach. The different reactivity of all the three double bonds present in the dipolarophile is reported. Finally, the mechanistic possibilities of [3 + 2]/[4 + 2] addition sequences involving the same reaction components in the case of cyclic and acyclic nitrones are explored extensively. The results suggest a novel and convenient routes for obtaining products of high selectivity with less energetic requirements. In some instances, new cycloadducts hitherto unreported are obtained.