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Combining meso-substitutions and core-modifications in the 28R → 30R hexaphyrin-based switch can synergistically improve the contrast between the nonlinear optical responses of the ON and OFF states by 10-fold compared to the unsubstituted switch.

Herein, the effects of an electric field on radicals are investigated for a set of model radicals with varying complexity. An electric field impacts the intrinsic philicity of a radical, as quantified by the global electrophilicity index, ω. The extent of change in philicity depends on the directionality and strength of the applied electric field and the dipole moment and polarizability of the radical.

Heteroaryl sulfonamides are important structural motifs in the medicinal and agrochemical industries. However, their synthesis often relies on the use of heteroaryl sulfonyl chlorides, which are unstable and toxic reagents. Herein, we report a protocol that allows direct oxidative coupling of heteroaryl thiols and primary amines, readily available and inexpensive commodity chemicals. The transformation proceeds under mild reaction conditions and yields the desired

Despite the large variety of modified nucleosides that have been reported, the preparation of constrained 4 '-spirocyclic adenosine analogues has received very little attention. We discovered that the [2+2]-cycloaddition of dichloroketene on readily available 4 '-exo-methylene furanose sugars efficiently results in the diastereoselective formation of novel 4 '-spirocyclobutanones. The reaction mechanism was investigated via density functional theory (DFT) and found to proceed either via a non-synchronous or stepwise reaction sequence, controlled by the stereochemistry at the 3 '-position of the sugar substrate. The obtained dichlorocyclobutanones were converted into nucleoside analogues, providing access to a novel class of chiral 4 '-spirocyclobutyl adenosine mimetics in eight steps from commercially available sugars. Assessment of the biological activity of designed 4 '-spirocyclic adenosine analogues identified potent inhibitors for protein methyltransferase target PRMT5.

Linear triatomic molecules (CO2, N2O, and OCS) are scrutinized for their propensity to form perpendicular tetrel (CO2 and OCS) or pnictogen (N2O) bonds with Lewis bases (dimethyl ether and trimethyl amine) as compared with their tendency to form end-on chalcogen bonds. Comparison of the IR spectra of the complexes with the corresponding monomers in cryogenic solutions in liquid argon enables to determine the stoichiometry and the nature of the complexes. In the present cases, perpendicular tetrel and pnictogen 1:1 complexes are identified mainly on the basis of the lifting of the degenerate ν 2 bending mode with the appearance of both a blue and a red shift. Van ′t Hoff plots of equilibrium constants as a function of temperature lead to complexation enthalpies that, when converted to complexation energies, form the first series of experimental complexation energies on sp1 tetrel bonds in the literature, directly comparable to quantum-chemically obtained values. Their order of magnitude corresponds with what can be expected on the basis of experimental work on halogen and chalcogen bonds and previous computational work on tetrel bonds. Both the order of magnitude and sequence are in fair agreement with both CCSD(T) and DFA calculations, certainly when taking into account the small differences in complexation energies of the different complexes (often not more than a few kJ mol−1) and the experimental error. It should, however, be noted that the OCS chalcogen complexes are not identified experimentally, most probably owing to entropic effects. For a given Lewis base, the stability sequence of the complexes is first successfully interpreted via a classical electrostatic quadrupole–dipole moment model, highlighting the importance of the magnitude and sign of the quadrupole moment of the Lewis acid. This approach is validated by a subsequent analysis of the molecular electrostatic potential, scrutinizing the σ and π holes, as well as the evolution in preference for chalcogen versus tetrel bonds when passing to “higher” chalcogens in agreement with the evolution of the quadrupole moment. The energy decomposition analysis gives further support to the importance/dominance of electrostatic effects, as it turns out to be the largest attractive term in all cases considered, followed by the orbital interaction and the dispersion term. The natural orbitals for chemical valence highlight the sequence of charge transfer in the orbital interaction term, which is dominated by an electron-donating effect of the N or O lone-pair(s) of the base to the central atom of the triatomics, with its value being lower than in the case of comparable halogen bonding situations. The effect is appreciably larger for TMA, in line with its much higher basicity than DME, explaining the comparable complexation energies for DME and TMA despite the much larger dipole moment for DME.

The screening of new molecules with high electron-donor properties is important for the design of new bioactive and technologically applicable substances. Here we propose diferulate (1), (Z)-2-(5-((E)-2-carboxyvinyl)-2-hydroxy-3-methoxyphenyl)-3-(4-hydroxy-3-methoxyphenyl)acrylic acid, to be an efficient electron donor which undergoes anodic conversion in aqueous media (pH 7) at around +0.15 V, vs. Ag|AgCl|3 M KCl. The low potential of oxidation of 1 indicates its high electron-donor capacity, which was documented by DPPH and ABTS radical scavenging and anti-lipoperoxidation activity analyses and also supported by in silico approaches. The results showed that compound 1, unlike ferulic acid 2 and the P1 benzofuranone synthetic precursor of 1, exhibits unique antiradical and antioxidant properties compared to trolox 3, which served as the positive control. No cytotoxic effects were observed for 1 in the 1–50 μM range. We conclude that the proposed structure 1 can be used for the further design of molecules whose biological (chemoprotective) activity is associated with high electron-donor properties.

In the last decade, halogen bonds, noncovalent interactions formed between positive regions in the electrostatic potential on halogen atoms, often referred to as sigma-holes, and electron-rich sites, have gained a lot of interest. Recently, this interest has been expanded towards interactions with GroupV and GroupVI elements, giving rise to pnicogen and chalcogen bonds. Although chalcogen bonds have already shown some promising results for applications in crystallography and catalysis, experimental results characterising these noncovalent interactions remain scarce. In this combined experimental and theoretical study, original data allowing the characterization of SO chalcogen bonds is obtained by studying the 1:1 molecular complexes between 2,2,4,4-tetrafluoro-1,3-dithiethane (C2F4S2) and dimethyl ether (DME). Ab initio calculations of the C2F4S2DME dimer yield two stable chalcogen-bonded isomers, the difference being the presence or absence of secondary FH interactions. Liquid-krypton solutions containing C2F4S2 and DME were studied using FTIR and Raman spectroscopy. Upon subtraction of rescaled monomer spectra, clear complex bands are observed. The observed complexation shifts agree favourably with the ab initio calculated shifts of the chalcogen-bonded complexes. The 1:1 stoichiometry of the complex is confirmed and a complexation enthalpy of -13.5(1)kJmol(-1) is found, which is in good agreement with the calculated values. A Ziegler-Rauk energy decomposition analysis revealed that electrostatic interactions prominently dominate over orbital interactions. Nevertheless, significant charge transfer occurs from the oxygen in DME to one of the sulfur atoms in C2F4S2 and the carbon along the extension of the chalcogen bond.

Using a set of state-of-the-art quantum chemical techniques we scrutinized the characteristically different reactivity of frustrated and classical Lewis pairs towards molecular hydrogen. The mechanisms and reaction profiles computed for the H2 splitting reaction of various Lewis pairs are in good agreement with the experimentally observed feasibility of H2 activation. More importantly, the analysis of activation parameters unambiguously revealed the existence of two reaction pathways through a low-energy and a high-energy transition state. An exhaustive scrutiny of these transition states, including their stability, geometry and electronic structure, reflects that the electronic rearrangement in low-energy transition states is fundamentally different from that of high-energy transition states. Our findings reveal that the widespread consensus mechanism of H2 splitting characterizes activation processes corresponding to high-energy transition states and, accordingly, is not operative for H2-activating systems. One of the criteria of H2-activation, actually, is the availability of a low-energy transition state that represents a different H2 splitting mechanism, in which the electrostatic field generated in the cavity of Lewis pair plays a critical role: to induce a strong polarization of H2 that facilities an efficient end-on acid-H2 interaction and to stabilize the charge separated “H+–H−” moiety in the transition state.

This study addresses one of the most important drawbacks inherently related to molecular searches in chemical compound space by greedy algorithms such as Best First Search and Genetic Algorithm, i.e., the large computational cost required to optimize one or more quantum-chemical properties. Significant speed-ups are obtained by initial property screening via predictive techniques starting already from very small databases. It is shown that the attainable acceleration depends heavily on the molecular properties, the predictive model, the molecular descriptor, and the current size of the database. We discuss the implementation and performance of predictive techniques in molecular searches based on a fixed molecular framework with a selection of sites to be filled with groups from a chemical fragment library. It is shown that for some properties speed-ups of a factor of 5 to even 20 can be obtained, while inverse design procedures on more complex properties still reach speed-ups of a factor of 2 without losing performance.

An efficient metal-free cascade reaction between 1-dibromovinyl-2-nitro-substituted arenes and secondary amines results in the formation of polycyclic pseudoindoxyls in a single step. The reaction mechanism leading to these fused ring systems was investigated, and is believed to involve the initial formation of nitroarylated ynamines/ynamides. These intermediates cycloisomerize towards N-alkenyl-tethered 2-aminoisatogens via a carbene intermediate as demonstrated by QTAIM (quantum theory of atoms in molecules) and ELF (electron localization function) analysis. A subsequent intramolecular dipolar cycloaddition afforded the title compounds.

Theoretical design can be an important aid in the discovery of valuable stable radical systems. In this study, inverse molecular design was applied to thiadiazinyl radicals to maximize two fundamental electronic properties in chemistry, namely electrophilicity and nucleophilicity. We discovered that the thiadiazinyl structure can be made moderately nucleophilic or highly electrophilic, depending on the electronic character of its substituents. The most electrophilic thiadiazinyl radical displays the highest electrophilic character encountered so far for uncharged radical systems. The accumulated data relating to the influence of different substituents at the various sites has allowed us to propose thiadiazinyl radicals that are intrinsically stable and as electrophilic or nucleophilic as possible. Although the nucleophilicity optimum fulfills the additional requirement of being stable, a significant drop from highly to merely moderately electrophilic is observed for the new electrophilicity optimum.

The chalcogen bond has been acknowledged as an influential noncovalent interaction (NCI) between an electron-deficient chalcogen (donor) and a Lewis base (acceptor). This work explores the main features of chalcogen bonding through a large-scale computational study on a series of donors and acceptors spanning a wide range in strength and character of this type of bond: (benzo)chalcogenadiazoles (with Ch = Te/Se/S) versus halides and neutral Lewis bases with O, N, and C as donor atoms. We start from Pearson's hard and soft acids and bases (HSAB) principle, where the hard nature of the chalcogen bond is quantified through the molecular electrostatic potential and the soft nature through the Fukui function. The σ-holes are more pronounced when going down in the periodic table and their directionality matches the structural orientation of donors and acceptors in the complexes. The Fukui functions point toward an n→σ*-type interaction. The initial conjectures are further scrutinized using quantum mechanical methods, mostly relating to the systems' electron density. A Ziegler–Rauk energy decomposition analysis shows that electrostatics plays a distinctly larger role for the soft halides than for the hard, uncharged acceptors, associated with the softness matching within the HSAB principle. The natural orbital for chemical valence analysis confirms the n→σ* electron donation mechanism. Finally, the electron density and local density energy at the bond critical point in the quantum theory of atoms in molecules study and the position of the spikes in the reduced density gradient versus density plot in the NCI theory situate the chalcogen bond in the same range as strong hydrogen bonds. © 2017 Wiley Periodicals, Inc.

Functionalized diamondoids show great potential as building blocks for various new optoelectronic applications. However, until now, only simple mono and double substitutions were investigated. In this work, we considered up to 10 and 6 sites for functionalization of the two smallest diamondoids, adamantane and diamantane, respectively, in search for diamondoid derivatives with a minimal and maximal HOMO-LUMO energy gap. To this end, the energy gap was optimized systematically using an inverse molecular design methodology based on the best-first search algorithm combined with a Monte Carlo component to escape local optima. Adamantane derivatives were found with HOMO-LUMO gaps ranging from 2.42 to 10.63 eV, with 9.45 eV being the energy gap of pure adamantane. For diamantane, similar values were obtained. The structures with the lowest HOMO-LUMO gaps showed apparent push-pull character. The push character is mainly formed by sulfur or nitrogen dopants and thiol groups, whereas the pull character is predominantly determined by the presence of electron-withdrawing nitro or carbonyl groups assisted by amino and hydroxyl groups via the formation of intramolecular hydrogen bonds. In contrast, maximal HOMO-LUMO gaps were obtained by introducing numerous electronegative groups.

The activation of N-methyl-D-aspartate receptors is found to be intimately associated with neurodegenerative diseases which make them promising therapeutic targets. Despite the significantly increasing multidisciplinary interests centred on this ionotropic channel, design of new ligands with intended functional activity remains a great challenge. In this article, a computational study based on density functional theory is presented to understand the structural factors of ligands determining their function as antagonists and partial agonists. With this aim, the GluN1 subunit is chosen as being one of the essential components in the activation mechanism, and quantum chemical calculations are implemented for 30 antagonists and 30 partial agonists known to bind to this subunit with different binding affinities. Several quantum chemical descriptors are investigated which might unlock the difference between antagonists and partial agonists.

There is an increasing interest in applying quantum chemistry to rationally design novel compounds with some desired characteristics. Furthermore, many applications require more than one property to be optimal. In this Concept, several inverse design strategies, based on the discrete best first search scheme, are introduced that allow for the simultaneous optimization of multiple properties or the optimization of the most vital target property with constraints for secondary properties. A detailed assessment of the different optimization techniques is carried out, and special attention is paid to improve the cost efficacy and performance by tuning the process parameters. Our suggested protocol allows for a more successful optimization routine when additional boundary conditions are desired.

Spin-polarized Conceptual DFT descriptors, such as the sum of the spin potentials and the spin-philicity index, are used to characterize the vertical and adiabatic singlet–triplet energy separation of silylenes and p-benzynes. In addition, an (approximately) intrinsic stability scale is constructed for both systems, using a model linking bond dissociation enthalpies to chemical concepts such as the electrophilicity index, Pauling’s electronegativity and the stability of the individual radical fragments, used with success in a recent contribution for radical systems. The new stability scales are compared to other scales in the literature and are correlated with the singlet–triplet gaps and the electrophilicity index values for the examined compounds, investigating the relationship between reactivity and stability.

The regioselectivity in the cyclopolymerization of diallyl monomers is investigated using DFT-based reactivity indices. In the first part, the experimentally observed mode of cyclization (exo versus endo) of 11 selected radicals involved in this process is reproduced by the computation of activation energies, entropies, enthalpies, and Gibb's free energies for the 5- and 6-membered cyclization reactions. The application of a recently proposed energy partitioning of the activation barriers shows that the regioselectivity cannot be explained by the steric effect alone. Next, a number of relevant DFT-based reactivity indices, such as non-spin-polarized and spin-polarized Fukui functions, spin densities, and dual descriptors, were applied to probe the role of the polar and stereoelectronic effects in this reaction. The dual descriptor has been found to reproduce best the experimental trends, confirming the important role of the stereoelectronic effects.

Radicals can be regarded as electrophilic/nucleophilic, depending on their tendency to attack sites of relatively higher/lower electron density. In this paper, an electrophilicity scale, global as well as local, and a nucleophilicity scale for 35 radicals is reported. The global electrophilicity scale correlates well with the nucleophilicity scale, suggesting that these concepts are inversely related.

The contributions of covalent and noncovalent interactions to the formation of classical adducts of bulky Lewis acids and bases and frustrated Lewis pairs (FLPs) were scrutinized by using various conceptual quantum chemical techniques. Significantly negative complexation energies were calculated for fourteen investigated Lewis pairs containing bases and acids with substituents of various sizes. A Ziegler–Rauk-type energy decomposition analysis confirmed that two types of Lewis pairs can be distinguished on the basis of the nature of the primary interactions between reactants; dative-bond formation and concomitant charge transfer from the Lewis base to the acid is the dominant and most stabilizing factor in the formation of Lewis acid–base adducts, whereas weak interactions are the main thermodynamic driving force (>50 %) for FLPs. Moreover, the ease and extent of structural deformation of the monomers appears to be a key component in the formation of the former type of Lewis pairs. A Natural Orbital for Chemical Valence (NOCV) analysis, which was used to visualize and quantify the charge transfer between the base and the acid, clearly showed the importance and lack of this type of interaction for adducts and FLPs, respectively. The Noncovalent Interaction (NCI) method revealed several kinds of weak interactions between the acid and base components, such as dispersion, π–π stacking, C[BOND]H⋅⋅⋅π interaction, weak hydrogen bonding, halogen bonding, and weak acid–base interactions, whereas the Quantum Theory of Atoms in Molecules (QTAIM) provided further conceptual insight into strong acid–base interactions.

Theoretical design can be an important aid in the discovery of valuable stable radical systems. In this study, inverse molecular design was applied to thiadiazinyl radicals to maximize two fundamental electronic properties in chemistry, namely electrophilicity and nucleophilicity. We discovered that the thiadiazinyl structure can be made moderately nucleophilic or highly electrophilic, depending on the electronic character of its substituents. The most electrophilic thiadiazinyl radical displays the highest electrophilic character encountered so far for uncharged radical systems. The accumulated data relating to the influence of different substituents at the various sites has allowed us to propose thiadiazinyl radicals that are intrinsically stable and as electrophilic or nucleophilic as possible. Although the nucleophilicity optimum fulfills the additional requirement of being stable, a significant drop from highly to merely moderately electrophilic is observed for the new electrophilicity optimum.

The contributions of covalent and noncovalent interactions to the formation of classical adducts of bulky Lewis acids and bases and frustrated Lewis pairs (FLPs) were scrutinized by using various conceptual quantum chemical techniques. Significantly negative complexation energies were calculated for fourteen investigated Lewis pairs containing bases and acids with substituents of various sizes. A Ziegler-Rauk-type energy decomposition analysis confirmed that two types of Lewis pairs can be distinguished on the basis of the nature of the primary interactions between reactants; dative-bond formation and concomitant charge transfer from the Lewis base to the acid is the dominant and most stabilizing factor in the formation of Lewis acid-base adducts, whereas weak interactions are the main thermodynamic driving force (>50 %) for FLPs. Moreover, the ease and extent of structural deformation of the monomers appears to be a key component in the formation of the former type of Lewis pairs. A Natural Orbital for Chemical Valence (NOCV) analysis, which was used to visualize and quantify the charge transfer between the base and the acid, clearly showed the importance and lack of this type of interaction for adducts and FLPs, respectively. The Noncovalent Interaction (NCI) method revealed several kinds of weak interactions between the acid and base components, such as dispersion, π-π stacking, C-H⋅⋅⋅π interaction, weak hydrogen bonding, halogen bonding, and weak acid-base interactions, whereas the Quantum Theory of Atoms in Molecules (QTAIM) provided further conceptual insight into strong acid-base interactions.

How the Conical Intersection Seam Controls Regioselectivity in the Photocycloaddition of Ethylene and Benzene

The photocycloaddition reaction of benzene with ethylene has been studied at the CASSCF level, including the characterization of an extended conical intersection seam. We show that the chemical selectivity is, in part, controlled by this extended conical intersection seam and that the shape of the conical intersection seam can be understood in terms of simple VB arguments. Further, the shape and energetics of the asynchronous segment of the conical intersection seam suggest that 1,2 (ortho) and 1,3 (meta) will be the preferred chemical products with similar weight. The 1,4 (para) point on the conical intersection is higher in energy and corresponds to a local maximum on the seam. VB analysis shows that the pairs of VB structures along this asynchronous seam are the same and thus the shape will be determined mainly by steric effects. Synchronous structures on the seam are higher in energy and belong to a different branch of the seam separated by a saddle point on the seam. On S1 we have documented three mechanistic pathways corresponding to transition states (with low barriers) between the reactants and the conical intersection seam: a mixed asynchronous/synchronous [1,2] ortho path, an asynchronous [1,3] meta path, and a synchronous [1,3] meta path.

The design of molecules with optimal properties is an important challenge in chemistry because of the astronomically large number of possible stable structures that is accessible in chemical space. This obstacle can be overcome through inverse molecular design. In inverse design, one uses the computation of certain indices to design molecules with an optimal target property. In this study, for the first time, inverse design was used to optimize reactivity properties of molecules. Specifically, we optimized the acidity of substituted 2-naphthols, both in the ground and the excited state. Substituted 2-naphthols belong to the class of photoacids, showing enhanced acidity when excited from the singlet ground state to the first singlet excited state. The focus of this work is the ground state. As a measure of acidity, three different properties are optimized: the charge on the hydroxyl hydrogen atom of the acid, the charge on the negatively charged oxygen atom of the conjugate base and the energy difference between acid and conjugate base. Both the practical use of the methodology and the results for ground and excited states are discussed.

Although extensive theoretical and experimental research has been conducted on fluorinated fullerenes, little detailed information exists on their solubility in different solvents. However, this solubility is crucial for their processability and possible application. In this work, we predict the solubility of fluorinated C(60) in various polar and non-polar solvents, based on a correlation between experimentally measured solubilities for C(60) from the literature and theoretically predicted solubilisation energies. These solubilisation energies are predicted using the polarizable continuum model (PCM) at the ab initio Hartree-Fock 6-31+G* level of theory. In particular, the solubilities are predicted for C(60)F(2)(n) (n = 1-10) isomers, part of the addition route to saturnene C(60)F(20). An increasing solubility is found for more polar solvents with higher degree of fluorination. With these results, we can determine the minimal fluorination degree necessary for possible solubilisation in a given solvent, and offer new perspectives to separate and purify species with different degrees of fluorination.

A detailed investigation of the kinetic irreversibility-reversibility concept is presented on the basis of the analysis of four side reactions occurring in the polymerization of poly(vinyl chloride), the intramolecular 1,5- and 1,6-backbiting and 1,2- and 2,3-Cl shift side reactions. Density functional theory-based reactivity indices combined with an analysis of the reaction force are invoked to probe this concept. The reaction force analysis is used to partition the activation and reaction energy and characterize the behavior of reactivity indices along the three reaction regions that are defined within this approach. It has been observed that in the reactant and product regions mainly geometric rearrangements take place, whereas in the transition state region changes in the electronic bonding pattern occur; here most changes of the electronic properties are observed. The kinetic irreversibility-reversibility of the reactions is confirmed and linked to the differences in the Fukui function and dual descriptor of the radical centers associated with the initial and final species.

Density functional theory (DFT) is a very popular and widely used methodology to investigate the electronic structure of many chemical systems having a variety of complexities.1–7 This theory uses the electron density function ρ(r) as the basic quantity from which all atomic and molecular properties...

In this work a complete and consistent set of 95 Benson group additive values (GAVs) for standard entropies S(o) and heat capacities C(p)(o) of hydrocarbons and hydrocarbon radicals is presented. These GAVs include 46 groups, among which 25 radical groups, which, to the best of our knowledge, have not been reported before. The GAVs have been determined from a set of B3LYP/6-311G(d,p) ideal gas statistical thermodynamics values for 265 species, consistently with previously reported GAVs for standard enthalpies of formation. One-dimensional hindered rotor corrections for all internal rotations are included. The computational methodology has been compared to experimental entropies (298 K) for 39 species, with a mean absolute deviation (MAD) between experiment and calculation of 1.2 J mol(-1) K(-1), and to 46 experimental heat capacities (298 K) with a resulting MAD = 1.8 J mol(-1) K(-1). The constructed database allowed evaluation of corrections on S(o) and C(p)(o) for non-nearest-neighbor effects, which have not been determined previously. The group additive model predicts the S(o) and C(p)(o) within approximately 5 J mol(-1) K(-1) of the ab initio values for 11 of the 14 molecules of the test set, corresponding to an acceptable maximal deviation of a factor of 1.6 on the equilibrium coefficient. The obtained GAVs can be applied for the prediction of S(o) and C(p)(o) for a wide range of hydrocarbons and hydrocarbon radicals. The constructed database also allowed determination of a large set of hydrogen bond increments, which can be useful for the prediction of radical thermochemistry.

Bond dissociation enthalpies (BDEs) of a large series of molecules of the type A-B, where a series of radicals A ranging from strongly electrophilic to strongly nucleophilic are coupled with a series of 8 radicals (CH2OH, CH3, NF2, H, OCH3, OH, SH, and F) also ranging from electrophilic to nucleophilic, are computed and analyzed using chemical concepts emerging from density functional theory, more specifically the electrophilicities of the individual radical fragments A and B. It is shown that, when introducing the concept of relative radical electrophilicity, an (approximately) intrinsic radical stability scale can be developed, which is in good agreement with previously proposed stability scales. For 47 radicals, the intrinsic stability was estimated from computed BDEs of their combinations with the strongly nucleophilic hydroxymethyl radical, the neutral hydrogen atom, and the strongly electrophilic fluorine atom. Finally, the introduction of an extra term containing enhanced Pauling electronegativities in the model improves the agreement between the computed BDEs and the ones estimated from the model, resulting in a mean absolute deviation of 16.4 kJ mol(-1). This final model was also tested against 82 experimental values. In this case, a mean absolute deviation of 15.3 kJ mol(-1) was found. The obtained sequences for the radical stabilities are rationalized using computed spin densities for the radical systems.

The unexpected nucleophilic reactivity of free-radicals generated from alpha-iodoketones is reported; two different procedures, either employing tin or the more environmentally acceptable ethylsulfone-based coupling reagent 5c have been developed.

Conceptual Density Functional Theory based Intrinsic Radical Stabilities: Application to Substituted Silylenes and p-benzynes". Invited contribution to the special issue "Concepts in DFT"

In this study, for the first time inverse design was applied to search for the intrinsically most stable radical system in a predefined chemical space of enormous size by scanning in a rational way that entire chemical space. The focus was predominantly on thermodynamic stabilization effects, such as stabilization through resonance. Two different properties were optimized: a newly introduced descriptor called the radical delocalization value and the intrinsic stability via a previously established bond dissociation enthalpy model. The thiadiazinyl radical was chosen as case study of this new approach of inverse design in stable radical chemistry. The resulting optimal structure is found to be highly stable, intrinsically more so than other well-known stable radicals, such as verdazyls and N,N-diphenyl-N′-picrylhydrazyl, and even rivaling the intrinsic stability of nitrogen monoxide.

We present a validation of computationally efficient density functional-based methods for the reproduction of relative bond dissociation energies of large polyaromatic hydrocarbons. Through the calculation of intrinsic radical stabilities and the computation of spin densities, the extent of delocalization of the unpaired electron in the benzylic radicals is examined. We focus on the influence of the level of theory choice applied for the geometry optimization and the role of van der Waals corrections on thermochemical properties. The dispersion effects mainly influence the energetics, causing a small upward shift of the bond dissociation energies. The long-range corrected CAM-B3LYP functional does not improve the traditional B3LYP results for the geometry description of the large delocalized radicals, however a non-negligible influence was encountered when applied for the energetics. It is reported that the f polarization functions present in the 6-311+G(3df,2p) basis set lead to an erroneous trend when combined with the B2PLYP functional for the computation of the single point energies.

Inverse design of molecules with optimal reactivity properties: acidity of 2-naphtol derivatives