Eric Assen B. Kantchev

Poly(3,4-ethylenedioxythiophene) (PEDOT) Nanobiointerfaces : Thin, Ultrasmooth, and Functionalized PEDOT Films with in Vitro and in Vivo Biocompatibility

Nanobiointerfaces were prepared based on an electrically conductive polyethylenedioxythiophene (PEDOT). Thin (<100 nm), ultrasmooth (roughness ( R(rms)) < 5 nm), and functionalized PEDOT films have been successfully electropolymerized using aqueous microemulsion. The microemulsion polymerization is found to be catalyzed in the presence of a low concentration of acid and allows for film formation from various functionalized ethylenedioxythiophenes (EDOTs) (e.g., EDOT-OH, C(2)-EDOT-COOH, C(4)-EDOT-COOH, C(2)-EDOT-NHS, EDOT-N(3)) and their mixtures. The nanobiointerfaces are compositionally tunable and controlled to deposit on selected electrode surfaces. They prefer orthogonal growth on patterned surfaces and are synthesized within seconds. These thin PEDOT films exhibit very low intrinsic cytotoxicity and display no inflammatory response upon implantation, making them ideal for biosensing and bioengineering applications.

Rational exploration of N-heterocyclic carbene (NHC) palladacycle diversity: a highly active and versatile precatalyst for Suzuki-Miyaura coupling reactions of deactivated aryl and alkyl substrates.

As less attention has been focussed on the design of highly efficient palladium precatalysts to ensure the smooth formation of the active catalyst for metal-mediated cross coupling reactions, we herein demonstrate that combining the bulky N-heterocyclic carbene (NHC) 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) with cyclopalladated acetanilide as the optimal palladium precatalyst leads to superior catalytic activity compared with the state-of-the-art NHC-Pd catalysts. The complex was discovered through the evaluation of a small, rationally designed library of NHC-palladacycles prepared by a novel, practical and atom-economic method, the direct reaction of IPrHCl with palladacycle acetate dimers.

Practical Heck-Mizoroki coupling protocol for challenging substrates mediated by an N-heterocyclic carbene-ligated palladacycle.

A highly active, N-heterocyclic carbene-palladacycle precatalyst for the Heck-Mizoroki reaction was rationally designed. The complex can be synthesized on a large scale in excellent yield by a novel, one-pot, three-component reaction and is tolerant to air, moisture, and long-term storage. A wide range of challenging substrates is successfully coupled under a simple and user-friendly reaction protocol.

Rhodium/diene-catalyzed tandem 1,4-shift/1,4-addition of (E)-1,2-diphenylethenylboronic acid to enones: density functional theory modeling and asymmetric catalysis

The conjugate addition of (E)-1,2-diphenylethenylboronic acid to 2-cyclohexenone in the presence of a diene/rhodium catalyst leads to a rearranged product incorporating a 2-((E)-2-phenylethenyl)phenyl group. The catalytic cycle involves a 1,4-Rh shift from the 1,2-diphenylethenylrhodium intermediate to form a new 2-((E)-2-phenylethenyl)phenylrhodium intermediate. DFT calculations demonstrate that the 1,4-Rh shift occurs via C–H oxidative addition and reductive elimination to/from a distorted square-pyramidal Rh(III)-hydride intermediate. The relative ΔG≠ of the 1,4-shift and carborhodation transition states are in good agreement with the experimentally observed selectivity.

Time-dependent density functional theory (TDDFT) modelling of Pechmann dyes: from accurate absorption maximum prediction to virtual dye screening.

The red Pechmann dye (λ(max) = 550 nm) is the exo-dimer of 4-phenyl-3-butenolide connected at the α-carbon by a double bond in a trans-fashion. The ring system is easily rearranged to the trans-endo-fused bicyclic 6-membered lactone dimer (yellow). Both lactones can be singly or doubly amidated with primary amines leading to further colour changes. The nature of the core heterocycle (exo- vs. endo-; 5- or 6-membered ring), core heteroatom (O vs. N) and additional substituents on the phenyl ring allows for exquisite control over colour achievable within a single dye family. Herein we present a detailed investigation of the modelling of the electronic spectra of the Pechmann dye family by time-dependent density functional theory (TDDFT). Whereas pure Hartree-Fock (TDHF) ab-initio calculation underestimates the UV/Vis absorption maximum, pure TDDFT leads to a large overestimation. The accuracy of the prediction is highly dependent on the mix of HF and DFT, with BMK (42% HF) and M06-2X (54% HF) giving the closest match with the experimental value. Among all basis sets evaluated, the computationally-efficient, DFT-optimized DGDZVP showed the best chemical accuracy/size profile. Finally, the dispersion interaction-corrected (SMD) implicit solvation model was found to be advantageous compared to the original IEFPCM. The absorption maxima of substituted Pechmann dyes and their rearranged lactone counterparts can be predicted with excellent accuracy (±6 nm) at the optimal SMD(toluene)/TD-BMK/DGDZVP//SMD(toluene)B3LYP/DGDZVP level of theory. Using this procedure, a small virtual library of novel, heterocycle-substituted Pechmann dyes were screened. Such substitution was shown to be a viable strategy for colour tuning, giving λ(max) from 522 (4-pyridyl) to 627 (2-indolyl) nm.

Cooperativity between steric repulsion and crossed diene coordination governs the enantioselectivity in rhodium(I)/chiral, 1,4- and 1,5-diene-catalysed 1,4-addition reaction: a DFT study

A comparative DFT (IEFPCM/PBE0/DGDZVP) study of the Rh-catalysed, enantioselective 1,4-addition of phenylboronic acid to 2-cyclohexenone with 11 known cyclic, chiral 1,4- and 1,5-diene ligands reveals a common pathway involving a transition state-less binding (EB) of 2-cyclohexenone to a [(diene)Rh–Ph] intermediate in a multitude of orientations leading to carborhodation (CR) via two competing, diastereomeric transition states (TS), which collapse to α-rhodioketones and then by further conformational reorganization to Rh-oxa-π-allyls. The energy difference between CR-TSs determines the enantioselectivity. DFT-predicted energy difference values are in good to excellent agreement with those derived from experimental enantiomeric excess values. Enantioselectivity was shown to be determined by a cooperative action of crossed diene coordination (measured by the angle formed by the two Rh-coordinated CC bonds in the ligand) and steric repulsion of the ligand substituents (e.g., phenyl) and 2-cyclohexenone. The cooperative effect is the strongest in the hitherto unknown 3,7-diphenylbicyclo[3.3.0]octa-2,6-diene, which was predicted to give the highest enantioselectivity of all ligands studied.

Thiophene-Containing Pechmann Dyes and Related Compounds: Synthesis, and Experimental and DFT Characterisation

Attaching 2-thienyl residues to the Pechmann dye core chromophore (5,5-exo-dilactone situated around a C-C double bond) results in a novel magenta-coloured compound (UV/Vis spectroscopy λ(max) =570 nm in CHCl(3)), which can be rearranged to a yellow 6,6-endo-dilactone (λ(max) =462 nm in CHCl(3)). Single and double amidation results in pronounced redshift in the 5,5-exo series (violet, λ(max) =570 nm and blue, λ(max) =606 nm in CHCl(3), respectively) but pronounced blueshift in the 6,6-endo series (yellow, λ(max) =424 nm and pale yellow bordering on colourless, λ(max) =395 nm in CHCl(3), respectively). Incorporation of a 3-alkyl substituent on the thiophene ring allows for sharp increase of solubility in organic solvents concomitant with fine-tuning of the colour: a redshift in 5,5-exo-dilactones but a blueshift in 5,5-exo-dilactams. DFT computations demonstrate that both lactone classes are planar regardless of the presence of a 3-alkyl group. The lactam derivatives are non-planar: the thiophene-core chromophore dihedral angles increase on going from 5,5-exo to 6,6-endo and from thiophene to 3-alkyl thiophene. Depending on the core heteroatom (O vs. N-alkyl), ring junction (5,5-exo vs. 6,6-endo) and 3-thiophene substituent (H vs. alkyl), two, three, four or six conformers are possible. All of these conformers were characterised by DFT and were found to be very close in energy at both IEFPCM/B3LYP/DGDZVP and SMD/M06/DGDZVP levels of theory. Within each conformer set, the HOMO and LUMO energies were within 0.05 eV and the predicted λ(max) values (TD-DFT) within 10 nm, and this implies low sensitivity of the optical and electronic properties to conformation. Cyclic voltammetry measurements of selected compounds demonstrated good matching to the HOMO and LUMO energies from IEFPCM/B3LYP/DGDZVP computations. M06-2X was the best DFT functional for TD-DFT, giving predicted λ(max) values within about 20 nm.

Thiophene-Containing Pechmann Dye Derivatives

Thiophene-containing Pechmann dyes (unsaturated exo-5,5-dilactones) were easily prepared by Cu-catalyzed dehydration of the corresponding β-aroylacrylic acids. Introduction of long alkyl chains greatly enhances solubility. Isomerization of an alkyl-substituted thiophene Pechmann dye (TPD) gave the corresponding endo-6,6-dilactone. The redox and electronic properties of these new dyes were investigated by CV, UV/vis, and fluorescence spectroscopy and DFT and TD-DFT computations. Strong absorption and emission in the visible region were recorded.

Copper-Catalyzed Regioselective 1,2-Alkylesterification of Dienes to Allylic Esters.

Copper catalyzed 1,2-alkylesterification of 1,3-dienes with diacyl peroxides affords branched allylic esters in excellent regioselectivity, including products with a newly generated fully substituted carbon center. The only byproduct is CO2. The reaction proceeds by a radical mechanism as suggested by spin trap and crossover experiments.

A First‐Principles Examination of the Asymmetric Induction Model in the Binap/RhI‐Catalysed 1,4‐Addition of Phenylboronic Acid to Cyclic Enones by Density Functional Theory Calculations

First-principles modelling of the diastereomeric transition states in the enantiodiscrimination stage of the catalytic cycle can reveal intimate details about the mechanism of enantioselection. This information can be invaluable for further improvement of the catalytic protocols by rational design. Herein, we present a density functional theory (IEFPCM/PBE0/DGDZVP level of theory) modelling of the carborhodation step for the asymmetric 1,4-arylation of cyclic α,β-unsaturated ketones mediated by a [(binap)Rh(I)] catalyst. The calculations completely support the older, qualitative, pictorial model predicting the sense of the asymmetric induction for both the chelating diphosphane (binap) and the more recent chiral diene (Phbod) ligands, while also permitting quantification of the enantiomeric excess (ee). The effect of dispersion interaction correction and basis sets has been also investigated. Dispersion-corrected functionals and solvation models significantly improve the predicted ee values.