Search

The cytochromes P450 are drug metabolizing enzymes in the body that typically react with substrates through a monoxygenation reaction. During the catalytic cycle two reduction and protonation steps generate a high-valent iron (IV)-oxo heme cation radical species called Compound I. However, with sufficient reduction equivalents present, the catalytic cycle should be able to continue to the reduced species of Compound I, called Compound II, rather than a reaction of Compound I with substrate. In particular, since electron transfer is usually on faster timescales than atom transfer, we considered this process feasible and decided to investigate the reaction computationally. In this work we present a computational study using density functional theory methods on active site model complexes alongside quantum mechanics/molecular mechanics calculations on full enzyme structures of cytochrome P450 enzymes. Specifically, we focus on the relative reactivity of Compound I and II with a model substrate for O&ndash, H bond activation. We show that generally the barrier heights for hydrogen atom abstraction are higher in energy for Compound II than Compound I for O&ndash, H bond activation. Nevertheless, for the activation of such bonds, Compound II should still be an active oxidant under enzymatic conditions. As such, our computational modelling predicts that under high-reduction environments the cytochromes P450 can react with substrates via Compound II but the rates will be much slower.

The reaction mechanisms for alkane hydroxylation catalyzed by non-heme FeVO complexes presented in the literature vary from rebound stepwise to concerted highly asynchronous processes. The origin of these important differences is still not completely understood. Herein, in order to clarify this apparent inconsistency, the hydroxylation of a series of alkanes (methane and substrates bearing primary, secondary, and tertiary CH bonds) through a FeVO species, [FeV(O)(OH)(PyTACN)]2+ (PyTACN = 1-(2′-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane), has been computationally examined at the gas phase and in acetonitrile solution. The initial breaking of the CH bond can occur via hydrogen atom transfer (HAT), leading to an intermediate where there is an interaction between the radical substrate and [FeIV(OH)2(PyTACN)]2+, or through hydride transfer to form a cationic substrate interacting with the [FeIII(OH)2(PyTACN)]+ species. Our calculations show the following: (i) except for methane in the rest of the alkanes studied, the intermediate formed by R+ and [FeIII(OH)2(PyTACN)]+ is more stable than that involving the alkyl radical and the [FeIV(OH)2(PyTACN)]2+ complex; (ii) in spite of (i), the first step of the reaction mechanism for all substrates is a HAT instead of hydride abstraction; (iii) the HAT is the rate-determining step for all analyzed cases; and (iv) the barrier for the HAT decreases along methane → primary → secondary → tertiary carbon. The second part of the reaction mechanism corresponds to the rebound process. Therefore, the stereospecific hydroxylation of alkane CH bonds by non-heme FeV(O) species occurs through a rebound stepwise mechanism that resembles that taking place at heme analogues. Finally, our study also shows that, to properly describe alkane hydroxylation processes mediated by FeVO species, it is essential to consider the solvent effects during geometry optimizations. The use of gas-phase geometries explains the variety of mechanisms for the hydroxylation of alkanes reported in the literature This work has been supported by Ministerio de Economiá y Competitividad of Spain (Projects CTQ2014-54306-P, CTQ2014-52525-P, and CTQ2012-37420-C02-01, Ramón y Cajal contract to A.C., and grant No. BES-2012-052801 to V.P.), Generalitat de Catalunya (project numbers 2014SGR931, 2014SGR862, Xarxa de Refereǹ cia en Quiḿ ica Teor̀ ica i Computacional, and ICREA Academia prizes for M.S. and M.C.), the European Commission (ERC-2009-StG-239910 to M.C. and FP7-PEOPLE-2011-CIG-303522 to A.C.), and European Fund for Regional Development (FEDER grant UNGI10-4E-801)

Aquest mateix article està publicat a l'edició alemanya d''Angewandte Chemie' (ISSN 0044-8249, EISSN 1521-3757), 2016, vol. 128, núm. 7, p. 2420-2423. DOI http://dx.doi.org/10.1002/ange.201509057 In this work, the Bingel-Hirsch addition of diethylbromomalonate to all non-equivalent bonds of Sc3N@D3h-C78 was studied using density functional theory calculations. The regioselectivities observed computationally allowed the proposal of a set of rules, the predictive aromaticity criteria (PAC), to identify the most reactive bonds of a given endohedral metallofullerene based on a simple evaluation of the cage structure. The predictions based on the PAC are fully confirmed by both the computational and experimental exploration of the Bingel-Hirsch reaction of Sc3N@D5h-C80, thus indicating that these rules are rather general and applicable to other isolated pentagon rule endohedral metallofullerenes We are grateful to the Spanish MINECO (CTQ2014-54306-P, CTQ2014-52525-P, CTQ2014-59212-P, and JdlC contract to S.O.), the Catalan DIUE (2014SGR931, ICREA Academia 2014 Award to M.S. and XRQTC), and the FEDER fund (UNGI10-4E-801) for financial support. M.G.-B. thanks the Spanish MECD for a PhD grant (AP2010-2517) and S.O. the European Commission for CIG project (FP7-PEOPLE-2013- CIG-630978). CESCA and BSC-CNS are acknowledged. M.R.C, M.I. and L.E. thanks the NSF for generous support of this work under grant (CHE-1408865) and to the NSFPREM program (DMR-1205302). The Robert A. Welch Foundation is also gratefully acknowledged for an endowed chair to L.E. (grant AH-0033)

Electrides are ionic substances containing isolated electrons. These confined electrons are topologically characterised by a quasi-atom, that is, a non-nuclear attractor (NNA) of the electron density. The electronic structure of the octahedral 4 A1g Li6+ and 5 A1g Be6 species shows that these species have a large number of NNAs. These NNAs have highly delocalised electron densities and, as a result, the chemical bonding pattern of these systems is reminiscent of that in solid metals, in which metal cations are surrounded by a "sea" of delocalised valence electrons. We propose the term metal cluster electrides to refer to this new class of compounds. In this study, we establish a computational protocol to identify, characterize, and design metal cluster electrides and we elucidate the intricate bonding patterns of this particular type of species.

Herein we describe the synthesis and characterization of a family of C-metalated aryl-Co(III) enolates, which can be considered as masked-carbenes, using diazoacetates as coupling partners. These species have been proved to be necessary intermediates in the C(sp2)-C(sp3) bond forming event to obtain cyclic amides, taming the elusive Co(III)-carbene species. The scope of diazoacetates has been exhaustively examined, varying the nature of the ester and the a-substitution, and a clear preference for electron-poor carbene precursors is observed. Exhaustive experimental and theoretical studies indicate that an unprecedented intramolecular SN2-type process governs the formation of the newly formed C-C bond. Furthermore, the key role of several Lewis acids as carboxylate-activating reagents is further explored by DFT calculations We acknowledge nancial support from the European Research Council for the Starting Grant Project ERC-2011-StG-277801 to X. R. and from MINECO of Spain for project CTQ2016-77989-P to A. C. and X. R. and project CTQ2014-52525-P to J. M. L. We also thank the Generalitat de Catalunya for projects 2017SGR264 and 2014SGR931

A new family of cobalt complexes with the general formula [CoII(OTf)2(Y,XPyMetacn)] (1R,Y,XPyMetacn ¼ 1-[(4-X-3,5-Y-2-pyridyl)methyl]-4,7-dimethyl-1,4,7-triazacyclononane, (X ¼ CN (1CN), CO2Et (1CO2Et), Cl (1Cl), H(1H), NMe2 (1NMe2)) where (Y ¼ H, and X ¼ OMe when Y ¼ Me (1DMM)) is reported. We found that the electronic tuning of the Y,XPyMetacn ligand not only has an impact on the electronic and structural properties of the metal center, but also allows for a systematic water-reduction-catalytic control. In particular, the increase of the electron-withdrawing character of the pyridine moiety promotes a 20-fold enhancement of the catalytic outcome. By UV-Vis spectroscopy, luminescence quenching studies and Transient Absorption Spectroscopy (TAS), we have studied the direct reaction of the photogenerated [IrIII(ppy)2(bpyc )] (PSIr) species to form the elusive CoI intermediates. In particular, our attention is focused on the effect of the ligand architecture in this elemental step of the catalytic mechanism. Finally, kinetic isotopic experiments together with DFT calculations provide complementary information about the rate-determining step of the catalytic cycle We would like to thank the European Commission for the ERCCG-2014-648304 (J.Ll.-F) project. The financial support from ICIQ Foundation and CELLEX Foundation through the CELLEXICIQ high throughput experimentation platform and the Starting Career Program is gratefully acknowledged. We also thank CERCA Programme (Generalitat de Catalunya); The MINECO is acknowledged for a FPU fellowship to A.C (AP2012- 6436) and ICIQ-IPMP program (F.F.) and Severo Ochoa Excellence Accreditation 2014–2018 (SEV-2013-0319). J.M.L. is grateful for financial support from the Spanish MINECO CTQ2014-52525-P and the Catalan DIUE 2014SGR931. J.P-P. gratefully acknowledge CTQ2014-60174-P (partially co-financed with FEDER funds), Maria de Maeztu (MDM-2015-0538), RyC contract to MGB) and Fundación Ramón Areces for financial support

Methods for the calculation of vibrational contributions to nonresonant and resonant linear and nonlinear optical properties of molecules are reviewed. Both the Bishop–Kirtman perturbation theory and the finite-field/nuclear relaxation–curvature approach are treated. Emerging methods using variational approaches instead of perturbation theory and the methodology required to employ curvilinear coordinates instead of the more usual normal coordinates are briefly described, too. Finally, methods using a time-dependent approach are also treated.

A novel hydroperoxoiron(III) species [Fe

Unraveling the mechanistic details of copper-catalyzed arylation of nucleophiles (Ullmann-type couplings) is a very challenging task. It is a matter of intense debate whether it is a radical-based process or an organometallic redox-based process. The ancillary ligand choice in Ullmann-type couplings plays a key role in such transformations and can strongly influence the catalytic efficiency as well as the mechanism. Here, we show how a predesigned tridentate pincer-like catalyst undergoes a deactivation pathway through a Cu

Ni-mediated trifluoromethylation of an aryl-Br bond in model macrocyclic ligands (L

The synthesis of endohedral metallofullerenes (EMFs) from a carbon soot sample leads to a variety of EMFs that are obtained in different relative abundances. In this work, we show that these abundances can be predicted from aromaticity calculations., The synthesis of endohedral metallofullerenes (EMFs) from a carbon soot sample of an arc discharge leads to a variety of EMFs that are obtained in different relative abundances. In the present work, we show that these abundances can be predicted from aromaticity calculations. In particular, we use the normalized Additive Local Aromaticity (ALAN) index. Our results show that the most abundant Sc3N-based and Y3N-based EMFs in fullerene soot are the most aromatic. This study reinforces the idea that aromaticity plays a key role in determining the stability of EMFs.

In this theoretical study we report on resonant and nonresonant electric-dipole (hyper)polarizabilities of cyanoacetylene molecule confined by repulsive potentials of cylindrical symmetry mimicking ...

Encapsulation of metal clusters in endohedral metallofullerenes takes place in cages that in most cases are far from being the most stable isomer in the corresponding hollow fullerenes. In large metal clusters and small fullerene cages, the election is mainly driven by the need to reduce strain. For the not so large metal clusters, it is usually said that the cage is chosen to minimize the electrostatic repulsion between charged five-membered rings.1 We have proved that maximizing the aromaticity is the main driving force that determines the most suitable hosting carbon cage for a given metallic cluster.2 This simple rule, the so-called Maximum ARomaticity Criterion (MARC), allow us to directly compare IPR (isolated pentagon rule) and non-IPR anionic isomers regardless the number of adjacent pentagon pairs (APP) they have. We have tested the MARC for the majority of endohedral metallofullerenes from C66 to C104 reported to date and the results show that MARC successfully predicts the most suitable C2n cage for hosting a given metal cluster among the manifold existing C2n isomers. In addition, using the Maximum ARomaticity Criterion, one can justify why the IPR rule is not always fulfilled when EMFs are considered. [Figure 1 here] Figure 1. Classification in terms of the ALA index of the anionic IPR and non-IPR fullerene isomers with 1-3 Adjacent Pentagon Pairs (APPs) for the most common C2 n (2n = 66–104) EMFs reported to date. Isomers experimentally observed are marked using black dots, and their corresponding isomer numbers are indicated. The ALA prediction ordering for the experimentally observed isomers are given in parentheses. A. Rodríguez-Fortea, N. Alegret, A.L. Balch, J.M. Poblet, Nat. Chem. 2010, 2, 955. M. Garcia-Borràs, S. Osuna, M. Swart, J.M. Luis, and M. Solà, Angew. Chem. Int. Ed. 2013, 52, 9275.

Meso‐aryl expanded porphyrins present a structural versatility that allows them to achieve different topologies with distinct aromaticities. Several studies appeared in the literature studying these topological switches from an experimental and theoretical point of view. Most of these publications include density functional theory calculations, being the B3LYP the most used methodology. In this work, we show that the selection of the functional has a critical role on the geometric, energetic, and magnetic results of these expanded porphyrins, and that the use of an inadequate methodology can even generate spurious stationary points on the potential energy surface. To illustrate these aspects, in this article we have studied different molecular distortions of two expanded porphyrins, [32]‐heptaphyrin and [26]‐hexaphyrin using 11 DFT functionals and performing single point energy calculations at the local pair natural orbital coupled cluster DLPNO‐CCSD(T) method, which have been carried out for benchmarking purposes. For some selected functionals, the dispersion effects have also been evaluated using the D3‐Grimme's dispersion correction with Becke–Johnson damping. Our results let us to conclude that the CAM‐B3LYP, M05‐2X, and M06‐2X functionals are the methodologies that provide a more consistent description of these topological switches, while other methods, such as B3LYP, BPE, and BP86, show a biased description., Ministerio de Economía y Competitividad of Spain . Grant Numbers: CTQ2016‐80375‐P , CTQ2014‐52525‐P , CTQ2014‐51912‐REDC -Universidad del País Vasco ‐ Euskal Herriko Unibertsitatea (UPV/EHU) . Grant Number: UFI11/22 QOSYC -Basque Government . Grant Number: IT673‐13 -Generalitat de Catalunya . Grant Number: 2014SGR139

Herein we describe the synthesis of a family of aryl-Co(III)-carboxylate complexes and their reactivity with ethyl di-azoacetate (EDA). Crystallographic, full spectroscopic characterization and theoretical evidence of unique C-metalated aryl-Co(III) enolate intermediates is provided, unraveling a carboxylate-assisted formation of aryl-Co(III) masked-carbenes. Moreover, additional evidence for an unprecedented Co(III)-mediated intramolecular SN2-type C-C bond formation in which the carboxylate moiety acts as a relay is disclosed. This novel strategy is key to tame the hot reactivity of a metastable Co(III)-carbene and elicit C-C coupling products in a productive manner We acknowledge financial support from the European Research Council for the Starting Grant Project ERC-2011- StG-277801 to X.R. and from MINECO of Spain for project CTQ2016-77989-P to A.C. and X.R., project CTQ2014-52525- P to J.M.L. and project CTQ2015-64436-P to T.P. We also thank Generalitat de Catalunya for projects 2014SGR862 and 2014SGR931

Unraveling the mechanistic details of copper-catalyzed arylation of nucleophiles (Ullmann-type couplings) is a very challenging task. It is a matter of intense debate whether it is a radical-based process or an organometallic redox- based process. The ancillary ligand choice in Ullmann-type couplings plays a key role in such transformations and can strongly influence the catalytic efficiency as well as the mechanism. Here, we show how a predesigned tridentate pincer-like catalyst undergoes a deactivation pathway through a Cu I /Cu III prototypical mechanism as demonstrated by helium-tagging infrared photodissociation (IRPD) spectroscopy and DFT studies, lending a strong support to the existence of an aryl-Cu III species in the Ullmann couplings using this tridentate ligand

One of the most important reactions in fullerene chemistry is the Diels-Alder (DA) reaction. In two previous experimental studies, the DA cycloaddition reactions of cyclopentadiene (Cp) and 1,2,3,4,5-pentamethylcyclopentadiene (Cp*) with La@C(2v)-C(82) were investigated. The attack of Cp was proposed to occur on bond 19, whereas that of Cp* was confirmed by X-ray analysis to be over bond o. Moreover, the stabilities of the Cp and Cp* adducts were found to be significantly different, that is, the decomposition of La@C(2v)-C(82)Cp was one order of magnitude faster than that of La@C(2v)-C(82)Cp*. Herein, we computationally analyze these DA cycloadditions with two main goals: First, to compute the thermodynamics and kinetics of the cycloadditions of Cp and Cp* to different bonds of La@C(2v)-C(82) to assess and compare the regioselectivity of these two reactions. Second, to understand the origin of the different thermal stabilities of the La@C(82)Cp and La@C(82)Cp* adducts. Our results show that the regioselectivity of the two DA cycloadditions is the same, with preferred attack on bond o. This result corrects the previous assumption of the regioselectivity of the Cp attack that was made based only on the shape of the La@C(82) singly occupied molecular orbital. In addition, we show that the higher stability of the La@C(82)Cp* adduct is not due to the electronic effects of the methyl groups on the Cp ring, as previously suggested, but to higher long-range dispersion interactions in the Cp* case, which enhance the stabilization of the reactant complex, transition state, and products with respect to the separated reactants. This stabilization for the La@C(82)Cp* case decreases the Gibbs reaction energy, thus allowing competition between the direct and retro reactions and making dissociation more difficult.

For the computation of rovibrational levels and their spectroscopic intensities, the Eckart conditions are essential to achieve the optimal separation between rotation and vibration. Dymarsky and Kudin [J. Chem. Phys. 122, 124103 (2005)] proposed a procedure for a simplified calculation of the Eckart rotation matrix. In the present work, we have adapted their approach to obtain a kinetic energy operator in curvilinear coordinates using a numerical but exact procedure without resorting to finite differences. Furthermore, we have modified this approach for the study of molecular systems with several minima, for which several Eckart reference geometries are required. The HONO molecular system has been used to show the efficiency of our implementation. Using the Eckart conditions with multi-reference geometries allows for a calculation of the rotational levels as well as frequencies and intensities of the infrared spectra of both HONO isomers with a single calculation.

The first examples of oxidant-free Au(I)-catalyzed halide exchange and halide-oxygen exchange reactions are described.

The electrides have a very special electronic structure with diffuse excess electrons not localized on any specific atom. Such systems are known to have huge electronic nonlinear optical (NLO) properties. Here, we determine and analyze the vibrational, as compared to the electronic, NLO properties for a representative set of electrides: Li@Calix, Na@Calix, Li@B 10H 14, Li 2 ·TCNQ ·-, and Na 2 ·TCNQ ·-. The static and dynamic vibrational (hyper)polarizabilities are computed by the nuclear relaxation method (with field-induced coordinates and the infinite optical frequency approximation) at the UB3LYP level using a hybrid Pople basis set. In general, the static vibrational β vec and γ ∥ exceed the corresponding static electronic property values by up to an order of magnitude. The same comparison for dynamic vibrational hyperpolarizabilities shows a smaller ratio. For the intensity-dependent refractive index (IDRI) and dc-Kerr processes, the ratio is on the order of unity or somewhat larger; it is less for the dc-Pockels and the electric field induced second harmonic (EFISH) effects (as well as the static α̂) but still important. The role of anharmonicity, motion of the alkali atoms, and substitution of Na for Li is discussed along with specific aspects of the charge distribution associated with the excess electron The following organizations are thanked for financial support: the Spanish Ministerio de Ciencia e Innovacion (MICINN, CTQ2011-23156/BQU) and the DIUE of the Generalitat de Catalunya (2009SGR637). M.G.-B. thanks the Spanish MEC for a doctoral fellowship, no. AP2010-2517. Support for the research of M.S. was received through the ICREA Academia 2009 prize for excellence in research funded by the DIUE of the Generalitat de Catalunya. Financial support from MICINN and the FEDER fund (European Fund for Regional Development) was provided by grant UNGI08-4E-003

The chemical functionalization of endohedral (metallo)fullerenes has become a main focus of research in the last few years. It has been found that the reactivity of endohedral (metallo)fullerenes may be quite different from that of the empty fullerenes. Encapsulated species have an enormous influence on the thermodynamics, kinetics, and regiochemistry of the exohedral addition reactions undergone by these species. A detailed understanding of the changes in chemical reactivity due to incarceration of atoms or clusters of atoms is essential to assist the synthesis of new functionalized endohedral fullerenes with specific properties. Herein, we report the study of the Diels-Alder cycloaddition between 1,3-butadiene and all nonequivalent bonds of the Ti(2)C(2)@D(3h)-C(78) metallic carbide endohedral metallofullerene (EMF) at the BP86/TZP//BP86/DZP level of theory. The results obtained are compared with those found by some of us at the same level of theory for the D(3h)-C(78) free cage and the M(3)N@D(3h)-C(78) (M=Sc and Y) metallic nitride EMFs. It is found that the free cage is more reactive than the Ti(2)C(2)@D(3h)-C(78) EMF and this, in turn, has a higher reactivity than M(3)N@D(3h)-C(78). The results indicate that, for Ti(2)C(2)@D(3h)-C(78), the corannulene-type [5,6] bonds c and f, and the type B [6,6] bond 3 are those thermodynamically and kinetically preferred. In contrast, the D(3h)-C(78) free cage has a preference for addition to the [6,6] 1 and 6 bonds and the [5,6] b bond, whereas M(3)N@D(3h)-C(78) favors additions to the [6,6] 6 (M=Sc) and [5,6] d (M=Y) bonds. The reasons for the regioselectivity found in Ti(2)C(2)@D(3h)-C(78) are discussed.

Recently, much attention has been focused on the design and synthesis of molecules with aromatic Möbius topology. One of the most promising applications is the manufacture of Hückel-to-Möbius topological optical switches with high nonlinear optical properties. In this work, we evaluate the electronic and vibrational contributions to static and dynamic nonlinear optical properties of the CS Hückel and C2 Möbius topologies synthesized by Herges and co-workers (Ajami, D. et al. Nature2003, 426, 819). Calculations are performed at the HF, B3LYP, BHandHLYP, BMK, M052X, CAM-B3LYP, and MP2 levels with the 6-31+G(d) basis set. Our results conclude that the BHandHLYP, M052X, and CAM-B3LYP methods correctly reproduce the X-ray crystal structure and provide similar nonlinear optical properties.

Oxo-transfer chemistry mediated by iron underpins many biological processes and today is emerging as synthetically very important for the catalytic oxidation of C–H and C=C moieties that are hard to activate conventionally. Despite the vast amount of research in this area, experimental characterization of the reactive species under catalytic conditions is very limited, although a Fe(V)=O moiety was postulated. Here we show, using variable-temperature mass spectrometry, the generation of a Fe(V)=O species within a synthetic non-haem complex at −40 °C and its reaction with an olefin. Also, with isotopic labelling we were able both to follow oxygen-atom transfer from H2O2/H2O through Fe(V)=O to the products and to probe the reactivity as a function of temperature. This study pioneers the implementation of variable-temperature mass spectrometry to investigate reactive intermediates We thank the Engineering and Physical Sciences Research Council and WestCHEM for funding, and Bruker Daltonics for collaboration. L. C. thanks the Royal Society and Wolfson Research for a merit award. M. C. and X. R. thank the Ministerio de Ciencia e Innovacion (MICINN) for Project CTQ2009-08464, and Generalitat de Catalunya for Institucio Catalana de Recerca i Estudis Avancats Academia Awards. M. C. thanks the European Research Foundation for Project ERC-2009-StG-239910. I. P. thanks MICINN for a PhD grant. L. C. and M. C. thank COST Action D40

A new response theory formulation for calculating second-order vibrational nonlinear optical properties has recently been presented by Hansen, et al. J. Chem. Phys. 2009, 131, 154101. For so-called mixed terms this method contains a correction to account for an approximation made in the classic Bishop and Kirtman, J. Chem. Phys. 1991, 15, 2646 perturbation treatment. This correction vanishes in the static limit and is here shown to vanish also in the high frequency limit. The response theory formulation is extended to third-order properties and, in that case, vanishes in both limits as well Financial help has been furnished by the Spanish MEC Project No. CTQ2008-06696/BQU and by the catalan Departament d’Universitats, Recerca i Societat de la Informació (DURSI) through project No. 2009SGR637

Recently, we reported that the basis set has a profound influence on the computed values for spin-state splittings [J. Phys. Chem. A 2008, 112, 6384]. In particular, small Gaussian-type orbital basis sets were shown to be unreliable for the prediction of them. Here, we report simple modifications of the small Pople-type Gaussian Type Orbital basis sets (3-21G, 3-21G*, 6-31G, 6-31G*), which correct their faulty behavior for the spin-state energies. We have investigated the basis sets for a set of thirteen first-row transition-metal complexes, for which reliable reference data have been obtained at the OPBE/TZ2P(STO) level. For several systems we have used single and double spin-contamination corrections to avoid ambiguity of the results due to spin-contamination, i.e. the energies and geometries were obtained for the pure spin states. The spin ground-states as predicted by the spin-state corrected GTO basis sets (s6-31G, s6-31G*) are in complete agreement with the reference STO data, while those of the original basis sets and a recent modification by Baker and Pulay (m6-31G*) are not for all cases. The spin-state corrected GTO basis sets also improve upon the original and modified basis sets for the accuracy of geometry optimization, while the accuracy of the vibrational frequencies is as good or better. At a limited additional cost, one therefore obtains very reliable results for these important spin-state energies We thank the following organizations for financial support: the Ministerio de Ciencia e Innovación (MICINN, project numbers CTQ2008-03077/BQU and CTQ2008-06532/BQU), the DIUE of the Generalitat de Catalunya (project numbers 2009SGR637 and 2009SGR528), and a research grant for MG (MICINN)

Peptidylglycine α-amidating monooxygenase and dopamine β-monooxygenase are copper-containing proteins which catalyze essential hydroxylation reactions in biological systems. There are several possible mechanisms for the reductive O2-activation at their mononuclear copper active site. Recently, Karlin and coworkers reported on the reactivity of a copper(II)–superoxo complex which is capable of inducing the hydroxylation of phenols with incorporated oxygen atoms derived from the Cu(II)-O2 ·− moiety. In the present work the reaction mechanism for the abovementioned superoxo complex with phenols is studied. The pathways found are analyzed with the aim of providing some insight into the nature of the chemical and biological copper-promoted oxidative processes with 1:1 Cu(I)/O2-derived species Financial help has been furnished by the Spanish Ministerio de Educación y Ciencia (MEC) projects No. CTQ2005-08797-C02-01/BQU and CTQ2008-03077/BQU and by the Catalan Department d’Universitats, Recerca i Societat de la Informació (DURSI) of the Generalitat de Catalunya project No. 2005SGR-00238

El mateix article està publicat en alemany a l'edició alemanya d' 'Angewandte Chemie' (ISSN 0044-8249, EISSN 1521-3757), 2016, vol. 128, núm. 22, p.6640–6644. DOI http://dx.doi.org/10.1002/ange.201601750 El títol de la versió postprint és "Introducing Fe and Mn as catalysts for the selective functionalization of Csp 2-H bonds of arenes by carbene insertion" The first examples of the direct functionalization of non-activated aryl sp2 C-H bonds with ethyl diazoacetate (N2CHCO2Et) catalyzed by Mn- or Fe-based complexes in a completely selective manner are reported, with no formation of the frequently observed cycloheptatriene derivatives through competing Buchner reaction. The best catalysts are FeII or MnII complexes bearing the tetradentate pytacn ligand (pytacn= 1-(2-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane). When using alkylbenzenes, the alkylic C(sp3)-H bonds of the substituents remained unmodified, thus the reaction being also selective toward functionalization of sp2 C-H bonds. Exclusive catalysis: Iron- and-manganese-based catalysts selectively functionalize the C(sp2)-H bonds of benzene or alkylbenzenes through the formal insertion of the CHCO2Et group from N2CHCO2Et (see scheme). When using alkylbenzenes, the alkylic C(sp3)-H bonds of the substituents remain unmodified Support for this work was provided by the MINECO (CTQ2014-52769-C3-R-1, CTQ2014-62234-EXP, CTQ2015-70795-P, CTQ2014-54306-P, and CTQ2014-52525P), and the Junta de Andaluc a (P10-FQM-06292)

Functionalization of endohedral metallofullerenes (EMFs) is an active line of research that is important for obtaining nanomaterials with unique properties that might be used in a variety of fields, ranging from molecular electronics to biomedical applications. Such functionalization is commonly achieved by means of cycloaddition reactions. The scarcity of both experimental and theoretical studies analyzing the exohedral regioselectivity of cycloaddition reactions involving EMFs translates into a poor understanding of the EMF reactivity. From a theoretical point of view, the main obstacle is the high computational cost associated with this kind of studies. To alleviate the situation, we propose an approach named the frozen cage model (FCM) based on single point energy calculations at the optimized geometries of the empty cage products. The FCM represents a fast and computationally inexpensive way to perform accurate qualitative predictions of the exohedral regioselectivity of cycloaddition reactions in EMFs. Analysis of the Dimroth approximation, the activation strain or distortion/interaction model, and the noncluster energies in the Diels–Alder cycloaddition of s-cis-1,3-butadiene to X@D3h-C78 (X = Ti2C2, Sc3N, and Y3N) EMFs provides a justification of the method The following organizations are thanked for financial support: the Ministerio de Ciencia e Innovacion (MICINN, Project Nos. CTQ2011-25086/BQU and CTQ2011-23156), and the DIUE of the Generalitat de Catalunya (Project Nos. 2009SGR637 and 2009SGR528). MG.-B. thanks the Spanish MEC for doctoral fellowship AP2010-2517. S.O. is grateful to the European Community for postdoctoral fellowship PIOF-GA-2009-252856. Excellent service by the Centre de Serveis Cientific i Academics de Catalunya (CESCA) is gratefully acknowledged. The authors also are grateful to the computer resources, technical expertise, and assistance provided by the Barcelona Supercomputing Center-Centro Nacional de Supercomputation. Support for the research of M.S. was received through the ICREA Academia 2009 prize for excellence in research funded by the DIUE of the Generalitat de Catalunya

Au has been demonstrated to mediate a number of organic transformations through the utilization of its π Lewis acid character, Au(I)/Au(III) redox properties or a combination of both. As a result of the high oxidation potential of the Au(I)/Au(III) couple, redox catalysis involving Au typically requires the use of a strong external oxidant. This study demonstrates unusual external oxidant-free Au(I)-catalyzed halide exchange (including fluorination) and Csp2-O bond formation reactions utilizing a model aryl halide macrocyclic substrate. Additionally, the halide exchange and Csp2-O coupling reactivity could also be extrapolated to substrates bearing a single chelating group, providing further insight into the reaction mechanism. This work provides the first examples of external oxidant-free Au(I)-catalyzed carbon-heteroatom cross-coupling reactions This work was supported by grants from the European Research Council (Starting Grant Project ERC-2011-StG-277801), the Spanish MINECO (CTQ2013-43012-P, Consolider-Ingenio CSD2010-00065, INNPLANTA project INP-2011-0059-PCT- 420000-ACT1) and Generalitat de Catalunya (2014 SGR 862)

Herein we show that species generated upon reaction of α-[Fe(CF3SO3)2(BPMCN)] (BPMCN = N,N′-bis(2-pyridylmethyl)-trans-1,2-diaminocyclohexane) with H2O2 (putatively [FeV(O)(OH)(BPMCN)]) is able to efficiently oxidize H2 to H2O even in the presence of organic substrates, while species formed in the presence of acetic acid (putatively [FeV(O)(OAc)(BPMCN)]) prefer organic substrate oxidation over H2 activation. Mechanistic implications have been analysed with the aid of computational methods., This work was supported by Spanish Ministerio de Economia y Competitividad (CTQ2012-37420-C02-02 and 01) European Research Council (StG 239910), and Generalitat de Catalunya(2014 SGR 862 and ICREA Academia award to MC). J.Ll.-F. thanks the CELLEX foundation for the starting career program for financial support.

A simplified model of the hardness kernel, η ( r → , r → ′ ) ≅ δ ( r → − r → ′ ) , has been evaluated for the calculation of the global hardness in a series of Lewis acids and bases using the MP2 method. It is found that this simple model yields the appropriate ordering of the molecules according to their hardness values when compared to experimental available results.

A number of different methods for calculation of vibrational energies are reviewed and tested for calculation of the fundamental vibrational frequencies for ethylene. The methods tested for the description of the vibrational states are vibrational self-consistent field (VSCF), vibrational configuration interaction (VCI), vibrational Moller-Plesset theory (VMP), and vibrational coupled cluster (VCC). The convergence of the different methods toward the full vibrational configuration interaction (FVCI) result is discussed for a modest-sized one-mode basis. For larger one-mode basis sets results are presented for selected methods. Different representations of the potential energy surface are compared including full and partial quartic force field as well as expansions using up to sixth derivatives of the potential energy surface. Using MP2 electronic structure theory, the electronic structure basis set convergence is tested. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem 104: 667- 680, 2005

In the present work, we have computed the energy and hardness profiles for a series of inter and intramolecular conformational changes at several levels of calculation. All processes studied have in common the fact that the choice of a weak methodology or a poor basis set results in the presence of spurious stationary points in the energy profile. At variance with the energy profiles, the hardness profiles calculated as the difference between the vertical ionization potential and electron affinity always show the correct number of stationary points independently of the basis set and methodology used. For this reason, we have concluded that hardness profiles can be used to check the reliability of the energy profiles for those chemical systems that, because of their size, cannot be treated with high level ab initio methods.

We present fully nonadiabatic as well as Born–Oppenheimer calculations of the dipole moments and static polarizabilites of LiH and LiD. The nonadiabatic calculations are done in a basis of explicitly correlated gaussian functions. The electronic Born–Oppenheimer values are corrected for vibrational contributions using the numerical Numerov–Cooley method including all orders of anharmonicity. A comparison between the two methods does not suggest any substantial disagreement in absolute values or the isotopic differences of the calculated properties.

We have studied how the calculation of electronic and vibrational contributions to nonlinear optical properties of three representative π-conjugated organic molecules is affected by the choice of basis set and the inclusion of electron correlation effects. The 6-31G basis does not always provide even qualitative accuracy. For semiquantitative accuracy a 6-31+G(d) basis is sufficient. Although, as compared to QCISD, a second-order Moller–Plesset (MP2) treatment often yields a substantial fraction of the electron correlation contribution, our MP2 results for the separate electronic and vibrational terms are not consistently of semiquantitative accuracy. Nevertheless, at the MP2 level the ratio between the vibrational and electronic contributions is satisfactorily reproduced.

The endohedral metallofullerenes (EMFs) and their exohedral functionalized derivatives present an increasing attention due to their potential applications in materials science and medicine. However, the current understanding of the reactivity of endohedral metallofullerenes is still very incomplete. In this chapter, we present a thorough study of the Diels-Alder (DA) reactivity of D 3h -C 78 , Sc3N@D 3h -C 78 , Y3N@D 3h -C 78 , Ti2C2@D 3h -C 78, Sc3N@D 5h -C 80 , Lu3N@D 5h -C 80 , Gd3N@D 5h -C 80 , Sc3N@I h -C 80 , Lu3N@I h -C 80 -C80, Gd3N@I h -C 80 , Y3N@I h -C 80 , La2@I h -C 80 , Y3@I h -C 80 , Sc3C2@I h -C 80 , Sc4C2@I h -C 80 , Sc3CH@I h -C 80 , Sc3NC@I h -C 80 , Sc4O2@I h -C 80 , Sc4O3@I h -C 80 , and La@C 2v -C 82. We have studied both the thermodynamic and the kinetic regioselectivity , taking into account when it was required the free rotation of the metallic cluster inside the fullerene. This systematic investigation was possible only because we use the Frozen Cage Model , which is a low-cost approach to determine the EMF exohedral regioselectivity. Our study has allowed the correction of two wrong experimental assignations of DA adducts, highlighting the key role of computational studies to achieve a deep understanding of exohedral reactivity of the EMFs. The incarceration of the metallic cluster reduces the reactivity of the EMFs respect to the hollow fullerenes. Our results also show that bond distances, pyramidalization angles , LUMOs shape, charge transfer , and cluster volume are the key factors that determine the DA regioselectivity of the fullerenes and EMFs. However, none of them can be used alone to predict which bond will be attacked. Finally, we focus our attention on the essential role of the dispersion interactions to reproduce the experimental results of the exohedral cycloaddition on EMFs.

Silver is extensively used in homogeneous catalysis for organic synthesis owing to its Lewis acidity, and as a powerful one-electron oxidant. However, two-electron redox catalytic cycles, which are most common in noble metal organometallic reactivity, have never been considered. Here we show that a Ag(I)/Ag(III) catalytic cycle is operative in model C–O and C–C cross-coupling reactions. An aryl-Ag(III) species is unequivocally identified as an intermediate in the catalytic cycle and we provide direct evidence of aryl halide oxidative addition and C–N, C–O, C–S, C–C and C–halide bond-forming reductive elimination steps at monometallic silver centres. We anticipate our study as the starting point for expanding Ag(I)/ Ag(III) redox chemistry into new methodologies for organic synthesis, resembling well-known copper or palladium cross-coupling catalysis. Furthermore, findings described herein provide unique fundamental mechanistic understanding on Ag-catalysed cross-coupling reactions and dismiss the generally accepted conception that silver redox chemistry can only arise from one-electron processes This work was supported by grants from the European Research Council (Starting Grant Project ERC-2011-StG-277801), the Spanish MINECO (CTQ2012-37420-C02-01/BQU, CTQ2012-32436, Consolider-Ingenio CSD2010-00065, INNPLANTA project INP-2011-0059-PCT-420000-ACT1) and the Catalan DIUE of the Generalitat de Catalunya (2009SGR637)

The encapsulation of metal clusters in endohedral metallofullerenes (EMFs) takes place in cages that in most cases are far from being the most stable isomer in the corresponding hollow fullerenes. There exist several possible explanations for the choice of the hosting cages in EMFs, although the final reasons are actually not totally well understood. Moreover, the reactivity and regioselectivity of (endohedral metallo)fullerenes have in the past decade been shown to be generally dependent on a number of factors, such as the size of the fullerene cage, the type of cluster that is being encapsulated, and the number of electrons that are transferred formally from the cluster to the fullerene cage. Different rationalizations of the observed trends had been proposed, based on bond lengths, pyramidalization angles, shape and energies of (un)occupied orbitals, deformation energies of the cages, or separation distances between the pentagon rings. Recently, in our group we proposed that the quest for the maximum aromaticity (maximum aromaticity criterion) determines the most suitable hosting carbon cage for a given metallic cluster (i.e. EMF stabilization), including those cases where the IPR rule is not fulfilled. Moreover, we suggested that local aromaticity plays a determining role in the reactivity of EMFs, which can be used as a criterion for understanding and predicting the regioselectivity of different reactions such as Diels-Alder cycloadditions or Bingel-Hirsch reactions. This review highlights different aspects of the aromaticity of fullerenes and EMFs, starting from how this can be measured and ending by how it can be used to rationalize and predict their molecular structure and reactivity The following organizations are thanked for financial support: the Ministerio de Ciencia e Innovacion (MICINN, project numbers CTQ2011-23156/BQU and CTQ2011-25086/BQU), the Generalitat de Catalunya (projects number 2009SGR637 and 2009SGR528 and Xarxa de Referencia en Quimica Teorica i Computacional), and the FEDER fund (European Fund for Regional Development) for the grant UNGI08-4E-003. M. G.-B. thanks the Spanish MEC for a doctoral fellowship no. AP2010-2517. S.O. thanks the MICINN for the Juan de la Cierva fellowship and the European Community for the CIG project (FP7-PEOPLE-2013-CIG-630978). The authors are also grateful to the computer resources, technical expertise, and assistance provided by the Barcelona Supercomputing Center Centro Nacional de Supercomputacion. Support for the research of M. Sola was received through the ICREA Academia 2009 prize for excellence in research funded by the DIUE of the Generalitat de Catalunya. Excellent service by the Centre de Serveis Cientifics i Academics de Catalunya (CESCA) is gratefully acknowledged

Static as well as dynamic electronic and vibrational longitudinal first hyperpolarizabilities ( and ) of α,ω,-nitro,amino-polyacetylene oligomers, containing up to 16 unit cells, have been computed at the Hartree−Fock and second-order Moller−Plesset levels using the 6-31G atomic basis set. The curve of first hyperpolarizability per unit cell versus the number of unit cells presents a maximum that defines the optimal chain length for NLO applications. Modifications in electronic structure occurring when electron correlation is included lead to an increase in the height of the maximum by a factor of 2. A similar enhancement arises from the corresponding change in equilibrium geometry, which, in addition, shifts the position of the maximum toward longer chain lengths. Frequency dispersion also has a major effect on the position and magnitude of the optimal point. The contribution of the vibrational hyperpolarizability is relatively small when correlation and frequency dispersion are included. Our results are...

Electrical property derivative expressions are presented for the nuclear relaxation contribution to static and dynamic (infinite frequency approximation) nonlinear optical properties. For CF4 and SF6, as opposed to HF and CH4, a term that is quadratic in the vibrational anharmonicity (and not previously evaluated for any molecule) makes an important contribution to the static second vibrational hyperpolarizability of CF4 and SF6. A comparison between calculated and experimental values for the difference between the (anisotropic) Kerr effect and electric field induced second-harmonic generation shows that, at the Hartree–Fock level, the nuclear relaxation/infinite frequency approximation gives the correct trend (in the series CH4, CF4, SF6) but is of the order of 50% too small.

The mechanism of copper-mediated Sonogashira couplings (so-called Stephens-Castro and Miura couplings) is not well understood and lacks clear comprehension. In this work, the reactivity of a well-defined aryl-Cu III species (1 ClO 4) with p-R-phenylacetylenes (R=NO2, CF3, H) is reported and it is found that facile reductive elimination from a putative aryl-CuIII-acetylide species occurs at room temperature to afford the Caryl - Csp coupling species (IR), which in turn undergo an intramolecular reorganisation to afford final heterocyclic products containing 2H-isoindole (PNO2, PCF3, PHa) or 1,2-dihydroisoquinoline (PHb) substructures. Density Functional Theory (DFT) studies support the postulated reductive elimination pathway that leads to the formation of C sp2-Csp bonds and provide the clue to understand the divergent intramolecular reorganisation when p-H-phenylacetylene is used. Mechanistic insights and the very mild experimental conditions to effect C aryl-Csp coupling in these model systems provide important insights for developing milder copper-catalysed Caryl - C sp coupling reactions with standard substrates in the future We acknowledge financial support from European Research Council for Starting Grant Project ERC-2011-StG-277801 to X. R., MICINN of Spain (INNPLANTA project INP-2011-0059-PCT-420000-ACT1 to X. R., CTQ2012-32436 to T. P., CTQ2012-37420-C02-01/BQU to Dr. M. Costas, RyC contract to J.Ll.-F. and PhD FPI grant to M. F.), Consolider-Ingenio CSD2010-00065, and the Catalan DIUE of the Generalitat de Catalunya (2009SGR637). X. R. thanks an ICREA-Academia award

An interesting reaction for the synthesis of aromatic carbo- and heterocycles is the transition-metal catalyzed [2 + 2 + 2] cycloaddition reaction. In this elegant and atom-efficient process three C-C or C-X (X = N, O, S...) bonds are formed in a single synthetic process. The [2 + 2 + 2] cycloaddition is catalyzed by a variety of organometallic complexes, including more than 15 different metals. In this work, we carry out computational studies of the reaction mechanism between two acetylenes and a nitrile to form substituted pyridines catalyzed by the Wilkinson complex. Our results show that initial oxidative addition between the two acetylene molecules is the rate-determining step. Oxidative addition between two acetylenes is more favorable than between acetylene and nitrile moieties. Our results are in agreement with the experimental finding that the formation of pyridines in some cases requires the use of an excess of nitrile. Nitriles with electron withdrawing substituents favor the incorporation of nitrile in the insertion process and improve the ratio of pyridine vs. benzene The following organizations are thanked for financial support: the Ministerio de Ciencia e Innovacion (MICINN, project numbers CTQ2011-23156/BQU and CTQ2011-23121 BQU), the Generalitat de Catalunya (projects number 2009SGR637, Xarxa de Referencia en Quimica Teorica i Computacional, and Fl PhD fellowship to O.T.), and the FEDER fund (European Fund for Regional Development) for the grant UNGI08-4E-003. Support for the research of M. S. was received through the ICREA Academia 2009 prize for excellence in research funded by the DIUE of the Generalitat de Catalunya

Recent studies have shown that non-heme iron complexes [Fe(L N4)X2], where LN4 stands for a tetradentate nitrogen based aminopyridine ligand (LN4 = Pytacn, mcp or mep, Pytacn = 1-(2-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane, mcp = N,N-dimethyl-N,N-bis(2-pyridylmethyl)cyclohexane-trans-1,2-diamine, mep = N,N-dimethyl-N,N-bis(2-pyridylmethyl)ethylendiamine), and X are monodentate ligands (X = Cl, CH3CN, CF3SO3 -, or H2O), catalyze the oxidation of water using cerium(IV) ammonium nitrate (CAN) as oxidant. Spectroscopic monitoring of catalytic water oxidation with [Fe(CF3SO3)2(Pytacn)] established [Fe IV(O)(OH2)(Pytacn)]2+ as an intermediate along the catalytic pathway, raising the question if these high valent species could be directly responsible for the O-O bond formation event. Herein, this question is addressed by a computational analysis of the thermodynamic and kinetic parameters associated with the reaction of non-heme iron complexes [Fe IV(O)(OH)(Pytacn)]+, [FeIV(O)(OH 2)(Pytacn)]2+, and [FeIV(OH)(OH)(Pytacn)] 2+ with water. Two different mechanisms have been studied for [FeIV(O)(OH)(Pytacn)]+; the nucleophilic water attack assisted by the hydroxyl group as internal base, which is the lowest energy path, and the external nucleophilic water attack. For [FeIV(OH)(OH) (Pytacn)]2+, only the attack assisted by the internal base has been studied, while in the case of [FeIV(O)(OH2)(Pytacn)] 2+, the only viable mechanism is the external nucleophilic water attack. Up to four water molecules were needed to be included in modeling of the O-O bond formation event for a proper description of the external nucleophilic water attack. The lowest Gibbs energy barrier and reaction free energy found for the direct water nucleophilic attack to the oxo ligand are of 32.2 and 28.3 kcal·mol-1 for [FeIV(O)(OH)(Pytacn)]+, 52.0 and 40.5 kcal·mol-1 for [FeIV(O)(OH 2)(Pytacn)]2+, and 28.3 and 28.3 kcal·mol -1 for [FeIV(OH)(OH)(Pytacn)]2+, respectively. These energy barriers and endergonic reaction energies are too high for the reaction to proceed and inconsistent with the relatively rapid reaction rates determined experimentally (δG‡ (exp.) = 17.6 kcal·mol-1). Therefore, this study provides strong evidence against the O-O bond formation by these species. The energetic accessibilities of FeV(O) and FeVI(O) intermediates have also been investigated, showing that FeV is the higher oxidation state accessible under catalytic conditions, consistent with our previous results We thank the European Research Foundation for Projects FP7-PEOPLE-2010-ERG-268445 (J.L.-F.) and ERC-2009-StG-239910 (M.C.), MICINN for projects CTQ2012-37420-C02-01/BQU (M.C.) and CTQ2011-23156/BQU (J.M.L.) and for a Ramon y Cajal contract (J.L.-F), and Generalitat de Catalunya for an ICREA Academia Award and Project 2009SGR637

In earlier work, the present authors have shown that hardness profiles are less dependent on the level of calculation than energy profiles for potential energy surfaces (PESs) having pathological b e- haviors. At variance with energy profiles, hardness profi les always show the correct number of stationary points. This characteristic has been used to indicate the existence of spurious stationary points on the PESs. In the present work, we apply this methodology to the hydrogen fluoride dimer, a classical diffi cult case for the density functional theory methods.

The chemical functionalization of endohedral metallofullerenes (EMFs) has aroused considerable interest due to the possibility of synthesizing new species with potential applications in materials science and medicine. Experimental and theoretical studies on the reactivity of endohedral metallofullerenes are scarce. To improve our understanding of the endohedral metallofullerene reactivity, we have systematically studied with DFT methods the Diels-Alder cycloaddition between s-cis-1,3-butadiene and practically all X@I h-C80 EMFs synthesized to date: X=Sc3N, Lu 3N, Y3N, La2, Y3, Sc 3C2, Sc4C2, Sc3CH, Sc3NC, Sc4O2 and Sc4O3. We have studied both the thermodynamic and kinetic regioselectivity, taking into account the free rotation of the metallic cluster inside the fullerene. This systematic study has been made possible through the use of the frozen cage model (FCM), a computationally cheap approach to accurately predicting the exohedral regioselectivity of cycloaddition reactions in EMFs. Our results show that the EMFs are less reactive than the hollow Ih-C80 cage. Except for the Y3 cluster, the additions occur predominantly at the [5,6] bond. In many cases, however, a mixture of the two possible regioisomers is predicted. In general, [6,6] addition is favored in EMFs that have a larger charge transfer from the metal cluster to the cage or a voluminous metal cluster inside. The present guide represents the first complete and exhaustive investigation of the reactivity of Ih-C80-based EMFs We are grateful for financial support from the Spanish MICINN (projects CTQ2011-23156/BQU and CTQ2011-25086/BQU), the Catalan DIUE (projects 2009SGR637, 2009SGR528, and XRQTC), and the FEDER fund (grant UNGI08-4E-003). M.G.-B. thanks the Spanish MECD for a Ph. D. fellowship (AP2010-2517) and S.O. thanks the European Community for a postdoctoral fellowship (PIOF-GA-2009-252856). Excellent service by CESCA is acknowledged. The authors are also grateful to the computer resources and assistance provided by the BSC-CNS. M.S. thanks the Catalan DIUE for the ICREA Academia 2009 Award

A quantitative analysis of the changes induced by solvation and static uniform electric fields on the potential energy surface of the SN2 Menshutkin-type reaction between ammonia and methyl chloride has been performed with the help of different indexes. These indexes have been defined to account for the structural and electronic degree of advance of the transition state with respect to the reactant complex and ion pair product through the use of geometrical parameters, dipole moments and electron density distributions. Indexes reveal that external perturbations yield transition states which are both electronically and structurally advanced as compared to the transition state in the gas phase. The overall study is complemented with HOMO-LUMO orbital considerations, quantification of the global charge density redistributions by means of quantum molecular self-similarity measures and an analysis of the topological features of electron density distributions.