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The binding of C-4-halogenated 1-(4-X-2,5-dimethoxyphenyl)-2-aminopropane (DOX) serotonin agonist psychedelics at all three 5-HT2receptor 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-HT2Aand 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.

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.

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 viaan 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.

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.

Typically, a Lewis acid and a Lewis base can react with each other and form a classical Lewis adduct. The neutralization reaction can however be prevented by ligating the acid and base with bulky substituents and the resulting complex is known as a “frustrated Lewis pair” (FLP). Since the Lewis acid and base reactivity remains in the formed complex, FLPs can display interesting chemical activities, with promising applications in catalysis. For example, FLPs were shown to function as the first metal-free catalyst for molecular hydrogen activation. This, and other recent applications of FLPs, have opened a new thriving research field. In this short-review, we recapitulate the computational and experimental studies of the H2activation by FLPs. We discuss the thus-far uncovered mechanistic aspects, including pre-organization of FLPs, the reaction paths for the activation, the polarization of HH bond and other factors affecting the reactivity. We aim to provide a rather complete mechanistic picture of the H2activation by FLPs, which has been under debate for decades since the first discovery of FLPs. This review is meant as a starting point for future studies and a guideline for industrial applications.

The differences between the first and second generation Grubbs catalysts have been the subject of much interest in olefin metathesis. In this direction, we revised in detail the dissociation reaction of 16e Grubbs precatalysts and the rotameric change between 14e inactive to active catalysts using a distortion/interaction model (called here the reorganization energy ΔEreorgand interaction energy ΔEint) combined with DFT-based reactivity descriptors. We have found that there are no great changes between both generations in terms of the interaction energies and electronic descriptors; however, a lower reorganization energy for the conformational change in the second generation was shown to be significant, in agreement with the reverse transeffect proposed recently, confirming that structural effects play a key role in the reactivity of these Ru-based complexes. Furthermore, the difference of the Grubbs catalysts in the formation of the ruthenacyclobutane intermediate, RCB, shows that the biradical species needed to generate this type of compound is more easily formed by the second generation than by the first, with ΔEreorg T–T(14)= −3.6 kcal mol−1vs.11.8 kcal mol−1, respectively. As a consequence, the different electronic features of the first and second generation Grubbs catalysts are manifested in the formation of ruthenacyclobutane intermediates, which allow us to propose that the higher catalytic activity of the second generation of Ru-based complexes also has its origin in these effects and not only in structural changes. Finally, we have also found that the dielectric polarizability change was shown to be a suitable property to describe the intensity of polarization effects in the formation of ruthenacyclobutane as well as in the identification of productive and non-productive processes.

Rhenium complexes are versatile molecular building blocks whose tunable photophysical properties are useful in diverse opto-related applications. Herein we report the synthesis and characterization of a novel ReItricarbonyldiimine complex, [(phen)Re(CO)3Br] (phen: 1,10-phenanthroline), which was found to be an efficient singlet oxygen [O2(1Δg)] photosensitizer in homogeneous solution [ΦO2(1Δg)= 0.55 (dichloromethane) and 0.16 (dimethylformamide)]. The photophysical properties of [(phen)Re(CO)3Br] were thoroughly characterized in solution and modeled by means of density functional theory (DFT) and time-dependent (TD)-DFT quantum mechanical calculations. The Re complex was incorporated into a flexible polymeric silsesquioxane (SSO) film, which has excellent dopant compatibility, chemical resistance, and mechanical properties. When [(phen)Re(CO)3Br] is embedded in the SSO film, it is found to retain most of the photophysical characteristics observed for the complex in solution. In particular, the [(phen)Re(CO)3Br]-doped SSO films were able to photosensitize O2(1Δg) when illuminated with blue light (∼405 nm). The O2(1Δg) sensitization by films in acetonitrile was followed by the photooxidation of the well-known O2(1Δg) chemical trap 9,10-dimethylanthracene (DMA) and confirmed by the direct observation of the O2(1Δg) luminescence spectrum (centered at 1270 nm) and the measurement of its kinetic profile. These results highlight the potential application of this type of polymeric material in the production of biological- or microbial-photoinactivating flexible surfaces or in the implementation of interfacial solid/liquid strategies for the photoinduced oxidation of organic compounds in solution.

Previous contributions concerning the computational approach to redox chemistry have made use of thermodynamic cycles and Car–Parrinello molecular dynamics simulations to obtain accurate redox potential values, whereas this article adopts a conceptual density functional theory (DFT) approach. Conceptual DFT descriptors have found widespread use in the study of thermodynamic and kinetic aspects of a variety of organic and inorganic reactions. However, redox reactions have not received much attention until now. In this contribution, we prove the usefulness of global and local electrophilicity descriptors for the prediction of the redox characteristics of first row transition metal ions (from Sc3+|Sc2+to Cu3+|Cu2+) and introduce a scaled definition of the electrophilicity based on the number of electrons an electrophile ideally accepts. This scaled electrophilicity concept acts as a good quantitative estimate of the redox potential. We also identify the first solvation sphere together with the metal ion as the primary active region during the electron uptake process, whereas the second solvation sphere functions as a non‐reactive continuum region.

We present results of density functional calculations for the standard reduction potential of the Ru3Ru2couple in aqueous solution. The metal cations are modeled as Ru(H2O)nqsurrounded by continuum solvent (q2, 3; n6, 18). The continuum model includes bulk electrostatic polarization as well as atomic surface tensions accounting for the deviation of the second or third hydration shell from the bulk. After consideration of 37 density functionals with 5 different basis sets, it has been found that hybrid and hybrid meta functionals provide the most accurate predictions for the Ru(H2O)nqgeometries and for the corresponding reduction potential in comparison with available experimental data. The gas-phase ionization potentials of Ru(H2O)n2calculated by density functional theory are also compared to results of ab initio computations using second-order Møller−Plesset perturbation theory. The difference in solvation free energies of Ru3and Ru2varies from −10.56 to −10.99 eV for n6 and from −6.83 to −7.45 eV for n18 depending on the density functional and basis set quality. The aqueous standard reduction potential is overestimated when only the first solvation shell is treated explicitly and is underestimated when the first and second solvation shells are treated explicitly.

Abstract: The concept of the reaction force is presented and discussed in detail. For typical processes with energy barriers, it has a universal form which defines three key points along an intrinsic reaction coordinate: the force minimum, zero and maximum. We suggest that the resulting four zones be interpreted as involving preparation of reactants in the first, transition to products in the second and third, and relaxation in the fourth. This general picture is supported by the distinctive patterns of the variations in relevant electronic properties. Two important points that are brought out by the reaction force are that (a) the traditional activation energy comprises two separate contributions, and (b) the transition state corresponds to a balance between the driving and the retarding forces.

The analytical application of a simple polarographic flow through cell, which was previously designed for the continuous polarographic analysis of organic compounds in pharmaceuticals and urine, is proposed in this work for the determination of copper in diluted water samples. The cell contains a conventional dropping mercury electrode (DME), a mercury pool and a platinum wire as the working, reference and counter electrodes, respectively. Enrichment of the analyte, previous to the polarographic continuous determination, was necessary and was achieved by using a microcolumn containing Chelex‐100, located in the loop of the injection valve. The flow through detector can be used either amperometrically, under continuous flow operation, or voltammetrically in quiet solution, under continuous flow‐stopped flow mode. Under continuous flow operation of the cell, after a preconcentration time of 3 min, the preconcentration factor was calculated to be 90, with a limit of detection of 9.5 ng/mL and a sampling rate of 15 h–1. The repeatability of the analytical signals, expressed as RSD, was always lower than 2.1%. Validation of the method was carried out by analysis of certified reference materials, and the recovery was 101.96±1.38%.

A simple design of a polarographic flow-through cell is proposed in which a conventional dropping mercury electrode (DME) is used as working electrode, and a mercury pool and a platinum wire are used as the reference and counter electrodes, respectively. The mercury droplets falling from the DME coalesce with the pool, and a fairly constant hold-up cell volume is achieved by controlled removal of the mercury from the pool at an equivalent flow rate than that of the DME. The analytical features of the cell are illustrated by flow-injection (FI) determination of the nitro derivative nifedipine in pharmaceuticals. The flow-through detector can be used either amperometrically, under continuous flow operation, or voltammetrically in quiet solution, under continuous flow-stopped flow mode. Under continuous flow operation of the cell, the sampling rate obtained was 120 h⁻¹. The repeatability of the analytical signals, expressed as RSD, was always lower than 2.1%. The recovery of nifedipine in synthetic tablet formulations was 99.8 ± 0.6%. © 1997 John Wiley & Sons, Inc. Lab Robotics and Automation 9: 255–262, 1997