Among the nine functionals benchmarked, the most accurate γ are obtained by Tα-LC-BLYP, reducing about half the errors of LC-BLYP.

Reactions that enable selective functionalization of strong aliphatic C−H bonds open new synthetic paths to rapidly increase molecular complexity and expand chemical space. Particularly valuable are reactions where site-selectivity can be directed toward a specific C−H bond by catalyst control. Herein we describe the catalytic site-and stereoselective γ-lactonization of unactivated primary C−H bonds in carboxylic acid substrates. The system relies on a chiral Mn catalyst that activates aqueous hydrogen peroxide to promote intramolecular lactonization under mild conditions, via carboxylate binding to the metal center. The system exhibits high site-selectivity and enables the oxidation of unactivated primary γ-C−H bonds even in the presence of intrinsically weaker and a priori more reactive secondary and tertiary ones at αand β-carbons. With substrates bearing nonequivalent γ-C−H bonds, the factors governing site-selectivity have been uncovered. Most remarkably, by manipulating the absolute chirality of the catalyst, γ-lactonization at methyl groups in gem-dimethyl structural units of rigid cyclic and bicyclic carboxylic acids can be achieved with unprecedented levels of diastereoselectivity. Such control has been successfully exploited in the late-stage lactonization of natural products such as camphoric, camphanic, ketopinic, and isoketopinic acids. DFT analysis points toward a rebound type mechanism initiated by intramolecular 1,7-HAT from a primary γ-C−H bond of the bound substrate to a highly reactive Mn IV -oxyl intermediate, to deliver a carbon radical that rapidly lactonizes through carboxylate transfer. Intramolecular kinetic deuterium isotope effect and 18 O labeling experiments provide strong support to this mechanistic picture.

This version is available at https://strathprints.strath.ac.uk/61289/ Strathprints is designed to allow users to access the research output of the University of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to the Strathprints administrator: strathprints@strath.ac.ukThe Strathprints institutional repository (https://strathprints.strath.ac.uk) is a digital archive of University of Strathclyde research outputs. It has been developed to disseminate open access research outputs, expose data about those outputs, and enable the management and persistent access to Strathclyde's intellectual output. Herein we study the hydroalkoxylation and hydrophenoxylation of alkynes using density functional theory calculations, and compare two possible mechanisms that have been proposed previously on the basis of theoretical and experimental studies, which unravel different preferences because of both the nature of the alkyne and alcohol, as well as the non-innocent role of the counter-anion of the dual gold based catalyst. Entropy is found to have a significant effect, rendering the nucleophilic attack of the monoaurated intermediate [Au(L)(η 2 -alkyne)] + difficult both kinetically and thermodynamically; this mechanism cannot easily form only the trans-alkene product that is observed experimentally. Instead, reaction via a dual gold catalysed mechanism presents much lower barriers. In addition, for the sake of direct comparison with recent results by Belanzoni, Zuccaccia, oversimplification of the Nheterocyclic carbene (NHC) ligand in the calculations might decrease the enthalpy barrier and lead to results that are not directly applicable to experiment. Moreover, the alkylic or arylic nature of the alkyne and/or alcohol is also tested. ORGANIC & BIOMOLECULAR CHEMISTRY ARTICLE

The shift towards renewable energy is one of the main challenges of this generation. Dye-sensitized solar cells (DSSC), based on donor-acceptor architectures, can help on this transition as they present...

In the oriented external electric-field-driven catalysis, the reaction rates and the selectivity of chemical reactions can be tuned at will. The activation barriers of chemical reactions within external electric fields of several strengths and directions can be computationally modeled. However, the calculation of all of the required field-dependent transition states and reactants is computationally demanding, especially for large systems. Herein, we present a method based on the Taylor expansion of the field-dependent energy of the reactants and transition states in terms of their field-free dipole moments and electrical (hyper)polarizabilities. This approach, called field-dependent energy barrier (FDB β ), allows systematic onedimensional (1D), two-dimensional (2D), and three-dimensional (3D) representations of the activation energy barriers for any strength and direction of the external electric field. The calculation of the field-dependent FDB β energy barriers has a computational cost several orders of magnitude lower than the explicit electric field optimizations, and the errors of the FDB β barriers are within the range of only 1−2 kcal•mol −1 . The achieved accuracy is sufficient for a fast-screening tool to study and predict potential electric-fieldinduced catalysis, regioselectivity, and stereoselectivity. As illustrative examples, four cycloadditions (1,3-dipolar and Diels−Alder) are studied.

We employ density functional theory (DFT) and time-dependent DFT (TDDFT) calculations to investigate the structural, energetic and optical properties of a new computationally designed RNA alphabet, where the nucleobases, A,G, C, andU (ts-bases), have been derived by replacing sulfur with selenium in the previously reported tz-bases, based on the isothiazolo[4,3-d]pyrimidine heterocycle core. We find out that the modeled non-natural bases have minimal impact on the geometry and energetics of the classical Watson-Crick base pairs, thus potentially mimicking the natural bases in a RNA duplex in terms of H-bonding. In contrast, our calculations indicate that H-bonded base pairs involving the Hoogsteen edge of purines are destabilized as compared to their natural counterparts. We also focus on the photophysical properties of the non-natural bases and correlate their absorption/emission peaks to the strong impact of the modification on the energy of the lowest unoccupied molecular orbital. It is indeed stabilized by roughly 1.1-1.6 eV as compared to the natural analogues, resulting in a reduction of the gap between the highest occupied and the lowest unoccupied molecular orbital from 5.3-5.5 eV in the natural bases to 3.9-4.2 eV in the modified ones, with a consequent bathochromic shift in the absorption and emission spectra. Overall, our analysis clearly indicates that the newly modelled ts-bases are expected to exhibit better fluorescent properties as compared to the previously reported tz-bases, while retaining similar H-bonding properties. In addition, we show that a new RNA alphabet based on size-extended benzo-homologated ts-bases can also form stable Watson-Crick base pairs with the natural complementary nucleobases.

C-F bonds are one of the most inert functionalities. Nevertheless, some [Cu2O2] 2+ species are able to defluorinatehydroxylate ortho-fluorophenolates in a chemoselective manner over other ortho-halophenolates. Albeit it is known that such reactivity is promoted by an electrophilic attack of a [Cu2O2] 2+ core over the arene ring, the crucial details of the mechanism that explain the chemo and regioselectivity of the reaction species remain unknown, and it has not being determined either if Cu II 2( 2 : 2 -O2) or Cu III 2(µ-O)2 species are responsible for the initial attack on the arene. Herein, we present a combined theoretical and experimental mechanistic study to unravel the origin of the chemo-selectivity of the ortho-defluorination-hydroxylation of 2-halophenolates by the [Cu2(O)2(DBED)2] 2+ complex. Our results show that the equilibria between (side-on)peroxo (P) and bis(μ-oxo) (O) isomers plays a key role in the mechanism, being the latter the reactive species. Furthermore, on the basis of quantum mechanical calculations, we have been able to rationalize the chemoselective preference of [Cu2(O)2(DBED)2] 2+ catalyst for the C-F activation over C-Cl and C-H activations.

Two oxoiron(IV) isomers ( R 2a and R 2b) of general formula [Fe IV (O)( R PyNMe 3 )(CH 3 CN)] 2 + are obtained by reaction of their iron(II) precursor with NBu 4 IO 4 . The two isomers differ in the position of the oxo ligand, cis and trans to the pyridine donor. The mechanism of isomerization between R 2a and R 2b has been determined by kinetic and computational analyses uncovering an unprecedented path for interconversion of geometrical oxoiron(IV) isomers. The activity of the two oxoiron(IV) isomers in hydrogen atom transfer (HAT) reactions shows that R 2a reacts one order of magnitude faster than R 2b, which is explained by a repulsive noncovalent interaction between the ligand and the substrate in R 2b. Interestingly, the electronic properties of the R substituent in the ligand pyridine ring do not have a significant effect on reaction rates. Overall, the intrinsic structural aspects of each isomer define their relative HAT reactivity, overcoming changes in electronic properties of the ligand.