Connection between nuclear and electronic Fukui functions beyond frontier molecular orbitals.

Based on the relationship between average local ionization energy I(r) and average local electron affinity A(r) with the electronic Fukui functions, i.e., f-(r) and f+(r), respectively, in this paper, we establish a connection between nuclear and electronic Fukui functions beyond frontier molecular orbitals. As a consequence of this connection, we obtain expressions of average nuclear Fukui functions interpreted as a variation of average nucleophilicity or electrophilicity (weighted by the electronic orbital Fukui functions) with respect to nuclear displacements, which goes beyond the highest occupied molecular orbital/or lowest unoccupied molecular orbital consideration. Furthermore, from this connection and considering the frontier molecular orbital approximation, we derive expressions of nuclear Fukui functions in terms of the atom-condensed electronic Fukui functions, which imply a locality in the chemical reactivity and could be used to study the variation of local nucleophilicity or electrophilicity with respect to nuclear displacements. Finally, this new way to interpret the nuclear Fukui function could be useful in the future to study the chemical reactivity related to molecular vibrations, internal rotations, bond dissociation, chemical reaction along the model of reaction coordinate, and so on.

A deeper analysis of the role of synchronicity on the Bell-Evans-Polanyi plot in multibond chemical reactions: a path-dependent reaction force constant.

The role of the degree of synchronicity in the formation of the new single-bonds in a large set of 1,3-dipolar cycloadditions and its relation in the fulfilment of the classical Bell-Evans-Polanyi principle and Hammond-Leffler postulate are deeply investigated. Our results confirm that asynchronicity is an important path-dependent factor to be taken into account: (i) the Bell-Evans-Polanyi is fulfilled as the degree of (a)synchronicity is quite the same, and a linear relationship between reorganisation energy and asynchronicity is found; (ii) the asynchronicity is the origin of deviations of this classical principle of chemical reactivity since any decrease of the energy barrier is due to an increase of asynchronicity at the same exothermicity; and (iii) the less exothermic the reaction is, the more asynchronous the mechanism is, at the same energy barrier. Thus, this implies that TS imbalance decreases the reorganisation energy, consequently affecting the reaction exothermicity as well.

5-HT2 Receptor Subfamily and the Halogen Bond Promise.

The binding of C-4-halogenated 1-(4-X-2,5-dimethoxyphenyl)-2-aminopropane (DOX) serotonin agonist psychedelics at all three 5-HT2 receptor subtypes is up to two orders of magnitude stronger for X = Cl, Br, or I (but not F) than when C-4 bears a hydrogen atom and more than expected from their hydrophobicities. Our docking and molecular dynamics simulations agree with the fact that increasing the polarizability of halogens results in halogen-oxygen distances to specific backbone C═O groups, and C-X···O angles, in ranges expected for halogen bonds (XBs), which could contribute to the high affinities observed. Good linear correlations are found for each receptor type, indicating that the binding pocket-ligand affinity is enhanced as the XB interaction becomes stronger (i.e., I ≈ Br > Cl > F). It is also striking to note how the linear equations unveil that the receptor's response on the strength of the XB interaction is quite similar among 5-HT2A and 5-HT2C, whereas the 5-HT2B's sensitivity is less. The calculated dipole polarizabilities in the binding pocket of the receptors reflect the experimental affinity values, indicating that less-polarizable and harder binding sites are more prone to XB formation.

1,3-Dipolar Cycloadditions by a Unified Perspective Based on Conceptual and Thermodynamics Models of Chemical Reactivity.

The main aim in the present report is to gain a deeper understanding of typical 1,3-dipolar cycloadditions by means of three chemical reactivity models in a unified perspective: conceptual density functional theory, distortion/interaction, and reaction force analysis. The focus is to explore the information provided by each reactivity model and how they complement or reinforce each other. Our results showed that the Bell-Evans-Polanyi (BEP) relationship is fulfilled, which is consistent with the Hammond-Leffler postulate. The electronic chemical potential based analysis classifies the reactions as HOMO-, HOMO/LUMO-, and LUMO-controlled reactions as the activation energy increases. It seems likely that HOMO-controlled reaction shifts into LUMO-controlled one as the transition state (TS) position does from early into late. Therefore, the transition from HOMO- (and early TS) into LUMO-controlled (and late TS) is paid by shifting the overall energy change into an endothermic direction, thus supporting the fulfillment of the BEP principle. While thermodynamic models unveil that the distortion or structural rearrangements mainly drive the activation barriers rather than interaction or electronic rearrangements in accord with the distortion/interaction and reaction force analysis, respectively. It is also found that both models are consistent when energy associated with structural and electronic reordering from reaction force analysis is respectively confronted with destabilizing (distortion and Pauli repulsion) and stabilizing (electrostatic and orbital interactions) contributions from the distortion/interaction model, which, on the other hand, increases as low activation barrier and high exothermicity are converted into the high barrier and low exothermicity along with the BEP relation. Finally, the reaction force constant reveals that all 1,3-dipolar cycloaddition reactions proceed by a synchronous single-step mechanism, unveiling that the degree of synchronicity is quite the same in all reactions, confirming the statement that BEP is fulfilled for similar reactions proceeding by a quite alike degree of synchronicity.

Unusual Oxidative Dealkylation Strategy toward Functionalized Phenalenones as Singlet Oxygen Photosensitizers and Photophysical Studies.

A series of functionalized 6-alkoxy phenalenones was prepared through an unprecedented oxidative dealkylation of readily available phenalene precursors. The starting phenalenes were efficiently synthesized via an aminocatalyzed annulation/O-alkylation strategy starting from simple substrates. The spectroscopic properties of some phenalenones were investigated in different solvents. Introducing an alkoxy substituent at the 6-position onto the phenalenone framework results in a red shift of the absorption. The synthesized phenalenones exhibit low fluorescence quantum yields, and the fluorescence decay was studied in different solvents, highlighting the presence of several lifetimes. The singlet oxygen (1O2) photosensitizing propensity of some phenalenones was investigated, and the results showed the striking importance of the phenalenone molecular structure in generating singlet oxygen with high yields. The ability of phenalenones to generate singlet oxygen was then harnessed in three photooxygenation reactions: anthracene oxidation, oxy-functionalization of citronellol through the Schenck-ene reaction, and photooxidation of a diene.

Real-Space Approach to the Reaction Force: Understanding the Origin of Synchronicity/Nonsynchronicity in Multibond Chemical Reactions.

In this article, we present a complementary analysis based on the reaction force F(ξ)/reaction force constant κ(ξ) and noncovalent interactions (NCI) index to characterize the energetics (kinetic and thermodynamics) and mechanistic pathways of two sets of multibond chemical reactions, namely, two double-proton transfer and two Diels-Alder cycloaddition reactions. This approach offers a very straightforward and useful way to delve into a deeper understanding of this type of process. While F(ξ) allows the partition of the whole pathway into three regions or phases, κ(ξ) describes how orchestrated are the bond-breaking and bond-formation events. In turn, NCI indicates how the inter- and intramolecular bonds evolve. The most innovative aspect is the inclusion of the formation of the reactant complex along the pathway, which, by means of NCI, unveils the early molecular recognition and the comprehension of its role in determining the degree of the synchronicity/nonsynchronicity of one-step processes. This approach should be a useful and alternative tool to characterize the energetics and the mechanism of general chemical reactions.

Scrutinizing the substituent effect on Mo-based electrocatalysts for molecular hydrogen release through axial-equatorial decomposition: a DFT study.

Based on the experimental precedent discovered by Kuranadasa and coworkers [H. I. Karunadasa et al., Nature, 2010, 464, 1329] to produce dihydrogen from water electrocatalyzed by 2,6-bis[1,1-bis(2-pyridyl)ethyl]-pyridine oxo-molybdenum complexes, we performed an extensive analysis to study the substituent group effect of derivatised compounds coming from the before mentioned Mo-based metal-organic cations in terms of two kinds of substitutions: axial and equatorial at the para-position of pyridine rings; several conceptual tools were used to back up our conclusions. We found that each type of substituent group (electron-withdrawing and electron-donating ones) exerts an independent influence on energetic parameters (energy barrier and overall energy). This opens the chance to search for a synergistic effect by combining these opposite behaviours of these substituents located in the equatorial and axial para-positions of pyridine rings to computationally modulate the aforementioned energetic parameters. This procedure will make easier the proposal of new catalysts to favour either kinetically or thermodynamically or in both ways the production of dihydrogen from water. Additionally, we encompassed a key point: the number of solvent molecules, so that including their presence in further investigations is mandatory.

Effect of the exchange-correlation functional on the synchronicity/nonsynchronicity in bond formation in Diels-Alder reactions: a reaction force constant analysis.

In this paper, we assess the performance of 24 density functional theory (DFT) based methods classified into 5 categories (GGA, MGGA, HGGA, HMGGA and DHGGA) in predicting reaction energetics, transition state geometries, and the degree of synchronicity/nonsynchronicity in the formation of two new C-C single-bonds in three Diels-Alder reactions between symmetrically and unsymmetrically substituted cyanoethylenes and cyclopentadiene, which gradually proceed from fully synchronous to highly asynchronous concerted mechanisms. This important concept in reaction mechanisms is revealed by the fine structure of the reaction force constant κ(ξ) along the transition region. Some wave function theory (WFT) based methods are also assessed against the CCSD(T) and CCSD benchmarks for the energy and geometry, respectively. The results and the statistical analysis of the errors confirm the robustness of SCS-MP2 (a WFT-based method) as one of the most reliable computational approaches. Regarding DFT-based methods, hybrid exchange-correlation functionals combined with medium-range electron correlation effects or long-range corrected exchange appear as the best performing methods, highlighting both M11 and M06-2X, since a certain percentage of exact Hartree-Fock exchange could counterbalance the delocalization errors that affect pure functionals. Thus, they reliably describe energetics, geometries and the degree of synchronicity in the formation of new C-C single bonds in Diels-Alder reactions. Noticeably, moderate performance for double hybrid functionals and poor performance for the most popular B3LYP method were found as well.

Hydrogenation of Multiple Bonds by Geminal Aminoborane-Based Frustrated Lewis Pairs.

The hydrogenation reaction of multiple bonds that is mediated by geminal aminoborane-based frustrated Lewis pairs (FLPs) has been explored by means of density functional theory calculations. It was found that the release of the activated dihydrogen occurred in a concerted, yet highly asynchronous, manner. The physical factors that control the transformation were quantitatively described in detail by using the activation strain model of reactivity in combination with the energy decomposition analysis method. This approach suggested a cooperative double hydrogen-transfer mechanism, which involves the initial migration of the protic (N)H followed by the nucleophilic attack of the (B)H hydride to the carbon atom of the multiple bond. The influence of both the substituents directly attached to the boron atom of the initial FLP and the nature of the multiple bond on the transformation was also investigated.

Deeper Insight into the Factors Controlling H2 Activation by Geminal Aminoborane-Based Frustrated Lewis Pairs.

H2 activation mediated by geminal aminoborane-based frustrated Lewis pairs (FLPs; R2 N-CH2 -BR'2 ) has been computationally explored within the density functional theory framework. It is found that the activation barrier of this process as well as the geometry of the corresponding transition states strongly depend on the nature of the substituents directly attached either to the acidic or the basic centers of the FLPs. The physical factors controlling the whole activation path are quantitatively described in detail by means of the activation strain model of reactivity combined with the energy decomposition analysis method. This methodology suggests a highly orbital-controlled mechanism where the degree of charge transfer cooperativity between the most important donor-acceptor orbital interactions, namely LP(N)→σ*(H2 ) and σ(H2 )→pπ (B), along the reaction coordinate constitutes a suitable indicator of the reaction barrier.

A computational and conceptual DFT study on the mechanism of hydrogen activation by novel frustrated Lewis pairs.

A computational and conceptual density functional theory (DFT) study on the mechanism of molecular hydrogen activation by a set of three frustrated Lewis pairs (FLPs) was performed at the ωB97X-D/6-311G(d,p) level of theory. A reduced model and other two prototypes derived from experimental data, based on the donor nitrogen and acceptor boron atoms, were used. Analysis based on the energy results, geometries and the global electron density transfer at the TSs made it possible to obtain some interesting conclusions: (i) despite the well-known very low reactivity of molecular hydrogen, the catalytic effectiveness of the three FLPs produces reactions with almost unappreciable activation energies; (ii) the reactions, being exothermic, follow a one-step mechanism via polarised TSs; (iii) there are neither substituent effects on the kinetics nor on the thermodynamics of these reactions; (iv) the activation of molecular hydrogen seems to be attained when the N-B distance in the FLP derivatives is around 2.74 Å; and (v) the proposed FLP model is consistent with the behaviour of the experimental prototypes. Finally, the ability of the three FLPs as efficient catalysts was evaluated studying the hydrogenation of acetylene to yield ethylene.

Complementarity of reaction force and electron localization function analyses of asynchronicity in bond formation in Diels-Alder reactions.

We have computationally compared three Diels-Alder cycloadditions involving cyclopentadiene and substituted ethylenes; one of the reactions is synchronous, while the others are slightly or highly asynchronous. Synchronicity and weak asynchronicity are characterized by the reaction force constant κ(ξ) having just a single minimum in the transition region along the intrinsic reaction coordinate ξ, while for high asynchronicity κ(ξ) has a negative maximum with minima on both sides. The electron localization function (ELF) shows that the features of κ(ξ) can be directly related to the formation of the new C-C bonds between the diene and the dienophile. There is thus a striking complementarity between κ(ξ) and ELF; κ(ξ) identifies the key points along ξ and ELF describes what is happening at those points.

Traditional and ion-pair halogen-bonded complexes between chlorine and bromine derivatives and a nitrogen-heterocyclic carbene.

A theoretical study of the halogen-bonded complexes (A-X···C) formed between halogenated derivatives (A-X; A = F, Cl, Br, CN, CCH, CF3, CH3, H; and X = Cl, Br) and a nitrogen heterocyclic carbene, 1,3-dimethylimidazole-2-ylidene (MeIC) has been performed using MP2/aug'-cc-pVDZ level of theory. Two types of A-X:MeIC complexes, called here type-I and -II, were found and characterized. The first group is described by long C-X distances and small binding energies (8-54 kJ·mol(-1)). In general, these complexes show the traditional behavior of systems containing halogen-bonding interactions. The second type is characterized by short C-X distances and large binding energies (148-200 kJ·mol(-1)), and on the basis of the topological analysis of the electron density, they correspond to ion-pair halogen-bonded complexes. These complexes can be seen as the interaction between two charged fragments: A(-) and (+)[X-CIMe] with a high electrostatic contribution in the binding energy. The charge transfer between lone pair A(LP) to the σ* orbital of C-X bond is also identified as a significant stabilizing interaction in type-II complexes.

The reaction force constant as an indicator of synchronicity/nonsynchronicity in [4+2] cycloaddition processes.

A variety of experimental and computational analyses support the concept that a chemical reaction has a transition region, in which the system changes from distorted states of the reactants to distorted states of the products. The boundaries of this region along the intrinsic reaction coordinate ξ, which includes the traditional transition state, are defined unambiguously by the minimum and maximum of the reaction force F(ξ), which is the negative gradient of the potential energy V(ξ). The transition region is characterized by the reaction force constant κ(ξ), the second derivative of V(ξ), being negative throughout. It has recently been demonstrated that the profile of κ(ξ) in the transition region is a sensitive indicator of the degree of synchronicity of a concerted reaction: a single κ(ξ) minimum is associated with full or nearly full synchronicity, while a κ(ξ) maximum (negative) between two minima is a sign of considerable nonsynchronicity, i.e. a two-stage concerted process. We have now applied reaction force analysis to the Diels-Alder cycloadditions of the various cyanoethylenes to cyclopentadiene. We examine the relative energy requirements of the structurally- and electronically-intensive phases of the activation processes. We demonstrate that the variation of κ(ξ) in the transition region is again indicative of the level of synchronicity. The fully synchronous cycloadditions are those in which the cyanoethylenes are symmetrically substituted. Unsymmetrical substitution leads to minor nonsynchronicity for monocyanoethylene but much more - i.e. two stages - for 1,1-dicyano- and 1,1,2-tricyanoethylene. We also show that the κ(ξ) tend to become less negative as the activation energies decrease.

New insights into H2 activation by intramolecular frustrated Lewis pairs based on aminoboranes: the local electrophilicity index of boron as a suitable indicator to tune the reversibility of the process.

A large set of intramolecular aminoborane-based FLPs was studied employing density functional theory in the H2 activation process to analyze how the acidity and basicity of boron and nitrogen atoms, respectively, affect the reversibility of the process. Three different linkers were employed, keeping the C-C nature in the connection between both Lewis centers: -CH2-CH2-, -CH[double bond, length as m-dash]CH-, and -C6H4-. The results show that significant differences in the Gibbs free energy of the process are found by considering all the combinations of substituents. Of the 75 systems studied, only 9 showed the ability to carry out the process reversibly (ΔGH2 in the range of -3.5 to 2.0 kcal mol-1), where combinations of alkyl/aryl or aryl/alkyl in boron/nitrogen generate systems capable of reaching reversibility. If the alkyl/alkyl or aryl/aryl combination is employed, highly exergonic (non-reversible H2 activation) and endergonic (unfeasible H2 activation) reactions are found, respectively. No appreciable differences in the linker were found, allowing us to continue the analysis with the most entropically favorable linker, the -C6H4- linker. From this, 25 different FLP systems of type 2-[bis(X)boryl]-(Y)aniline (X: H, CF3, C6F5, PFtB, FMes and Y: H, CH3, t-but, Ph, Mes) can be formed. By analyzing the electronic properties of each system, we have found that the condensed-to-boron electrophilicity index ωB+ is inversely related to the ΔGH2. Interestingly, two relationships were found; the first is for alkyl groups (Y: CH3 and t-but) and the second for aryl groups (Y: H, Ph, and Mes), which is intimately related to the proton affinity of each aniline. In addition, it is quite interesting when the frustration degree, given by B⋯N distance dB-N, is brought together with ωB+, since the quotient has unit energy/length corresponding to unit force; concomitantly, a measure of the FLP strength in H-H bond activation can be defined. With this finding, a rational design of this kind of FLP can be performed by analyzing the acidity of boron through condensed-to-boron electrophilicity and knowing the nature of the substituent of nitrogen according to whether the Y is alkyl or aryl, optimizing the H2 reversible activation in a rational way, which is crucial to improve the catalytic performance.

Unconventional OFF-ON Response of a Mono(calix[4]arene)-Substituted BODIPY Sensor for Hg2+ through Dimerization Reversion.

A new selective fluorogenic chemosensor for Hg2+, which combines a calixarene derivative with a BODIPY core as a fluorescent reporter, is described. The remarkable change in its fluorogenic properties in DMSO and CHCl3 has been analyzed. A study of its spectral properties on dilution, along with molecular modeling studies, allowed us to explain that this behavior involves the formation of a J-dimer, as well as how the sensing mechanism of Hg2+ proceeds.

The reaction force constant: an indicator of the synchronicity in double proton transfer reactions.

Earlier work, both experimental and computational, has drawn attention to the transition region in a chemical reaction, which includes the traditional transition state but extends along the intrinsic reaction coordinate ξ from perturbed forms of the reactants to perturbed forms of the products. The boundaries of this region are defined by the reaction force F(ξ), which is the negative gradient of the potential energy V(ξ) of the system along ξ. The reaction force constant κ(ξ), the second derivative of V(ξ), is negative throughout the transition region. We have now demonstrated, for a series of twelve double proton transfer processes, that the profile of κ(ξ) in the transition region is an indicator of the synchronicity of the two proton migrations in each case. When they are fully or nearly fully synchronous, κ(ξ) has a single minimum in the transition region. When the migrations are considerably nonsynchronous, κ(ξ) has two minima separated by a local maximum. Such an assessment of the degree of synchronicity cannot readily be made from an examination of the transition state alone, nor it is easily detected in the profiles of V(ξ) and F(ξ).

Theoretical analysis based on X-H bonding strength and electronic properties in red- and blue-shifting hydrogen-bonded X-H···π complexes.

A theoretical study based on the X-H bond strength of the proton donor fragment and its concomitant classical red-shifting or improper blue-shifting of the pure stretching frequency, in weakly hydrogen-bonded X-H···π complexes, is presented. In this sense, the dissociation energy differences, defined as, ΔD(e) = D(e)(X-H)[complex] - D(e)(X-H) [isolated], showed to be linearly connected with the change in stretching frequencies, Δν = ν(X-H)[complex] - ν(X-H)[isolated], of red- and blue-shifting H-bonds. This relationship allows us to define a threshold for the type of the stretching shift of the X-H bond: ΔD(e)(X-H) > 50.3 kcal mol(-1) leads to blue-shifting whereas ΔD(e)(X-H) < 50.3 kcal mol(-1) leads to red-shifting behavior. Complementarily, natural bond orbital analysis along the X-H stretching coordinate and electric dipole polarizability was performed to investigate the factors involved in red- or blue-shifting hydrogen-bonded complexes. It has been found that a high tendency to deplete the electronic population on the H atom upon X-H stretching is exhibited in blue-shifting H-bonded complexes. On the other hand, these types of complexes present a compact electronic redistribution in agreement with polarizability values. This study has been carried out taking as models the following systems: chloroform-benzene (Cl(3)C-H···C(6)H(6)), fluoroform-benzene (F(3)C-H···C(6)H(6)), chloroform-fluorobenzene, as blue-shifting hydrogen-bonded complexes and cyanide acid-benzene (NC-H···C(6)H(6)), bromide and chloride acids-benzene ((Br)Cl-H···C(6)H(6)) and acetylene-benzene (C(2)H(2)···C(6)H(6)) as red-shifting complexes.

Regioselectivity of radical additions to substituted alkenes: insight from conceptual density functional theory.

Radical additions to substituted alkenes are among the most important reactions in radical chemistry. Nonetheless, there is still some controversy in the literature about the factors that affect the rate and regioselectivity in these addition reactions. In this paper, the orientation of (nucleophilic) radical additions to electron-rich, -neutral, and -poor monosubstituted substrates (11 reactions in total) is investigated through the use of chemical concepts and reactivity descriptors. The regioselectivity of the addition of nucleophilic radicals on electron-rich and -neutral alkenes is thermodynamically controlled. An excellent correlation of 94% is found between the differences in activation barriers and in product stabilities (unsubstituted versus substituted site attack). Polar effects at the initial stage of the reaction play a significant role when electron-poor substrates are considered, lowering the extent of regioselectivity toward the unsubstituted sites, as predicted from the stability differences. This is nicely confirmed through an analysis for each of the 11 reactions using the spin-polarized dual descriptor, matching electrophilic and nucleophilic regions.

Elucidating sensing mechanisms of a pyrene excimer-based calix[4]arene for ratiometric detection of Hg(ii) and Ag(i) and chemosensor behaviour as INHIBITION or IMPLICATION logic gates.

This article reports the synthesis and characterisation of two lower rim calix[4]arene derivatives with thiourea as spacer and pyrene or methylene-pyrene as fluorophore. Both derivatives exhibit a fluorimetric response towards Hg2+, Ag+ and Cu2+. Only methylene-pyrenyl derivative 2 allows for selective detection of Hg2+ and Ag+ by enhancement or decrease of excimer emission, respectively. The limits of detection of 2 are 8.11 nM (Hg2+) and 2.09 nM (Ag+). DFT and TD-DFT computational studies were carried out and used to identify possible binding modes that explain the observed response during fluorescence titrations. Calculations revealed the presence of different binding sites depending on the conformation of 2, which suggest a reasonable explanation for non-linear changes in fluorescence depending on the physical nature of the interaction between metal centre and conformer. INHIBITION and IMPLICATION logic gates have also been generated monitoring signal outputs at pyrene monomer (395 nm) and excimer (472 nm) emission, respectively. Thus 2 is a potential primary sensor towards Ag+ and Hg2+ able to configure two different logic gate operations.