Impact of Heterocycle Annulation on NIR Absorbance in Quinoid Thioacene Derivatives.

The synthesis and characterisation of a homologous series of quinoid sulfur-containing imidazolyl-substituted heteroacenes is described. The optoelectronic and magnetic properties were investigated by UV/vis, fluorescence and EPR spectroscopy as well as quantum-chemical calculations, and were compared to those of the corresponding benzo congener. The room-temperature and atmospherically stable quinoids display strong absorption in the NIR region between 678 and 819 nm. The dithieno[3,2-b:2',3'-d]thiophene and the thieno[2',3':4,5]thieno[3,2-b]thieno[2,3-d]thiophene derivatives were EPR active at room temperature. For the latter, variable-temperature EPR spectroscopy revealed the presence of a thermally accessible triplet state, with a singlet-triplet separation of 14.1 kJ mol-1 .

Tailoring the Gibbs Free Energy of the Nitroxide Exchange Reaction: Substituent and Solvent Effects.

A quantum chemical study of the nitroxide exchange reaction is presented. Inspired by the recent use of this reaction in the synthesis of dynamic covalent polymer networks, we studied the influence of substituents and solvents on the Gibbs free energy, which plays a crucial role for both the reversibility of the reaction and the extent of product formation. We provide accurate benchmark values based on CCSD(T) and COSMO-RS theory for a series of structural modifications and make suggestions for improving the molecular building blocks used so far.

Two-photon absorption in a series of 2,6-disubstituted BODIPY dyes.

We report on the two-photon absorption spectra of a series of 2,6-disubstituted BODIPY dyes. Depending on the substituents, we observe increasing two-photon absorption cross sections with values up to 350 GM compared to 70 GM in the unsubstituted dye. Quantum chemical calculations are performed to assign the absorption bands and to understand the factors controlling the size of the two-photon absorption cross section. Both the maximum of the two-photon absorption band as well as the red-shift of the whole spectrum correlate with the ability of the substituents to extend the π-electron system of the dye. The above-mentioned intense two-photon absorption band corresponds to the absorption of photons with 1.3 eV, which is at the first near-infrared transparency window for biological tissues. The dyes could thus be suitable for bio-imaging applications.

Aluminium Diphosphamethanides: Hidden Frustrated Lewis Pairs.

The synthesis and characterisation of two aluminium diphosphamethanide complexes, [Al(tBu)2 {κ(2) P,P'-Mes*PCHPMes*}] (3) and [Al(C6 F5 )2 {κ(2) P,P'-Mes*PCHPMes*}] (4), and the silylated analogue, Mes*PCHP(SiMe3 )Mes* (5), are reported. The aluminium complexes feature four-membered PCPAl core structures consisting of diphosphaallyl ligands. The silylated phosphine 5 was found to be a valuable precursor for the synthesis of 4 as it cleanly reacts with the diaryl aluminium chloride [(C6 F5 )2 AlCl]2 . The aluminium complex 3 reacts with molecular dihydrogen at room temperature under formation of the acyclic σ(2) λ(3) ,σ(3) λ(3) -diphosphine Mes*PCHP(H)Mes* and the corresponding dialkyl aluminium hydride [tBu2 AlH]3 . Thus, 3 belongs to the family of so-called hidden frustrated Lewis pairs.

Modeling the Histidine-Phenylalanine Interaction: The NH···π Hydrogen Bond of Imidazole·Benzene.

NH···π hydrogen bonds occur frequently between the amino acid side groups in proteins and peptides. Data-mining studies of protein crystals find that ∼80% of the T-shaped histidine···aromatic contacts are CH···π, and only ∼20% are NH···π interactions. We investigated the infrared (IR) and ultraviolet (UV) spectra of the supersonic-jet-cooled imidazole·benzene (Im·Bz) complex as a model for the NH···π interaction between histidine and phenylalanine. Ground- and excited-state dispersion-corrected density functional calculations and correlated methods (SCS-MP2 and SCS-CC2) predict that Im·Bz has a Cs-symmetric T-shaped minimum-energy structure with an NH···π hydrogen bond to the Bz ring; the NH bond is tilted 12° away from the Bz C6 axis. IR depletion spectra support the T-shaped geometry: The NH stretch vibrational fundamental is red shifted by -73 cm(-1) relative to that of bare imidazole at 3518 cm(-1), indicating a moderately strong NH···π interaction. While the S0(A1g) → S1(B2u) origin of benzene at 38 086 cm(­1) is forbidden in the gas phase, Im·Bz exhibits a moderately intense S0 → S1 origin, which appears via the D(6h) → Cs symmetry lowering of Bz by its interaction with imidazole. The NH···π ground-state hydrogen bond is strong, De=22.7 kJ/mol (1899 cm­1). The combination of gas-phase UV and IR spectra confirms the theoretical predictions that the optimum Im·Bz geometry is T shaped and NH···π hydrogen bonded. We find no experimental evidence for a CH···π hydrogen-bonded ground-state isomer of Im·Bz. The optimum NH···π geometry of the Im·Bz complex is very different from the majority of the histidine·aromatic contact geometries found in protein database analyses, implying that the CH···π contacts observed in these searches do not arise from favorable binding interactions but merely from protein side-chain folding and crystal-packing constraints. The UV and IR spectra of the imidazole·(benzene)2 cluster are observed via fragmentation into the Im·Bz+ mass channel. The spectra of Im·Bz and Im·Bz2 are cleanly separable by IR hole burning. The UV spectrum of Im·Bz2 exhibits two 000 bands corresponding to the S0 → S1 excitations of the two inequivalent benzenes, which are symmetrically shifted by -86/+88 cm(-1) relative to the 000 band of benzene

Unprecedented pseudo-ortho and ortho metallation of [2.2]paracyclophanes--a methyl group matters.

The first example of a pseudo-ortho metallation on [2.2]paracyclophane is presented, giving easy access to enantiopure compounds of this type. By slight modification of the directing group, metallation of the ortho- and C2-positions is possible. The mechanism was further investigated by means of density functional theory (DFT) calculations.

Activation enthalpies and entropies of the atropisomerization of substituted butyl-bridged biphenyls.

A combined quantum chemical and experimental study of the atropisomerization energies of di-para-substituted butyl-bridged biphenyl cyclophanes is presented. We studied the influence of electron donor and electron acceptor substituents on the height of the enantiomerization barrier and examined the enthalpic and entropic contributions. The reaction pathway with minimum and transition state structures was established using density functional theory calculations. The Gibbs free activation energies derived from this pathway correspond well to the ones determined by temperature dependent high performance liquid chromatography (HPLC) measurements. Surprisingly, large discrepancies were found for the contributions of enthalpy and entropy. Thermodynamic data derived from circular dichroism (CD) measurements support the quantum chemical calculations for the distribution of enthalpy and entropy, contrary to the HPLC measurements. Rationalizations for this are given.

Oriented circular dichroism analysis of chiral surface-anchored metal-organic frameworks grown by liquid-phase epitaxy and upon loading with chiral guest compounds.

Oriented circular dichroism (OCD) is explored and successfully applied to investigate chiral surface-anchored metal-organic frameworks (SURMOFs) based on camphoric acid (D- and Lcam) with the composition [Cu2(Dcam)(2x)(Lcam)(2-2x)(dabco)]n (dabco = 1,4-diazabicyclo-[2.2.2]-octane). The three-dimensional chiral SURMOFs with high-quality orientation were grown on quartz glass plates by using a layer-by-layer liquid-phase epitaxy method. The growth orientation, as determined by X-ray diffraction (XRD), could be switched between the [001] and [110] direction by using either OH- or COOH-terminated substrates. These SURMOFs were characterized by using OCD, which confirmed the ratio as well as the orientation of the enantiomeric linker molecules. Theoretical computations demonstrate that the OCD band intensities of the enantiopure [Cu2(Dcam)2(dabco)]n grown in different orientations are a direct result of the anisotropic nature of the chiral SURMOFs. Finally, the enantiopure [Cu2(Dcam)2(dabco)]n and [Cu2(Lcam)2(dabco)]n SURMOFs were loaded with the two chiral forms of ethyl lactate [(+)-ethyl-D-lactate and (-)-ethyl-L-lactate)]. An enantioselective enrichment of >60 % was observed by OCD when the chiral host scaffold was loaded from the racemic mixture.

Asymmetric organocatalytic synthesis of 4,6-bis(1H-indole-3-yl)-piperidine-2 carboxylates.

We developed an asymmetric organocatalytic synthesis of 4,6-bis(1H-indole-3-yl)-piperidine-2-carboxylates using 10 mol% of a chiral phosphoric acid. The products, which are novel bisindole-piperidine-amino acid hybrids, can be obtained in one step from 3-vinyl indoles with imino esters in dichloromethane at room temperature after 1 h of reaction time. A variety of these compounds could be synthesized in up to 70% yield and 99% ee, and they were experimentally and computationally analyzed regarding their relative and absolute stereochemistry.

Tethering for selective synthesis of 2,2'-biphenols: the acetal method.

2,2'-Biphenols are a large and diverse group of compounds with exceptional properties both as ligands and bioactive agents. Traditional methods for their synthesis by oxidative dimerisation are often problematic and lead to mixtures of ortho- and para-connected regioisomers. To compound these issues, an intermolecular dimerisation strategy is often inappropriate for the synthesis of heterodimers. The 'acetal method' provides a solution for these problems: stepwise tethering of two monomeric phenols enables heterodimer synthesis, enforces ortho regioselectivity and allows relatively facile and selective intramolecular reactions to take place. The resulting dibenzo[1,3]dioxepines have been analysed by quantum chemical calculations to obtain information about the activation barrier for ring flip between the enantiomers. Hydrolytic removal of the dioxepine acetal unit revealed the 2,2'-biphenol target.

ortho-Perfluoroalkylation and ethoxycarbonyldifluoromethylation of aromatic triazenes.

A robust protocol for perfluoroalkylation and ethoxycarbonyldifluoromethylation of functionalized aromatic triazenes is described. Using silver(I)-fluoride and different fluorinated (trimethyl)silyl substituted species, it was possible to synthesize various ortho-fluorinated triazenes in good yields via simple CH-substitution. Initial reactions under solvent-free (neat) conditions indicate a stabilizing interaction between "AgRf" and the triazene moiety, which may be responsible for the good yields and regioselectivity. The transformation possibilities of the triazene moiety make these reactions interesting for the synthesis of fluorinated building blocks. In addition, quantum chemical calculations suggest that the stabilization of the radical intermediate in the ortho-position is distinctly more favored for aromatic triazenes than for other aromatic substrates.

Atropisomerization of di-para-substituted propyl-bridged biphenyl cyclophanes.

The influence of electron donors and electron acceptors of variable strength in the 4 and 4' position of 2 and 2' propyl-bridged axial chiral biphenyl cyclophanes on their atropisomerization process was studied. Estimated free energies ΔG(‡)(T) of the rotation around the central biphenyl bond which were obtained from (1)H-NMR coalescence measurements were correlated to the Hammett parameters σ(p) as a measure for electron donor and acceptor strength. It is demonstrated that the resulting nice linear correlation is mainly based on the influence of the different substituents on the π-system of the biphenyl cyclophanes. By lineshape analysis the rate constants were calculated and by the use of the Eyring equation the enthalpic and entropic contributions were evaluated. Density functional theory calculations show a planar transition state of the isomerization process and the calculated energy barriers based on this reaction mechanism are in good agreement with the experimentally obtained free energies.

The plakotenins: biomimetic Diels-Alder reactions, total synthesis, structural investigations, and chemical biology.

The total synthesis of plakotenin, a cytotoxic marine natural product, using a biomimetic Diels-Alder reaction is described in detail. Two approaches were used, whereby the Diels-Alder reaction occurs at different stages of the synthesis. Homo- and nor-plakotenin, related natural products, were also prepared, as well as iso-plakotenin, a diastereoisomer of plakotenin. The syntheses prove the relative and absolute stereochemistry of the latter. The chemical biology of the plakotenins was investigated on selected compounds.

Structure revision of plakotenin based on computational investigation of transition states and spectroscopic properties.

We show that the previously [Tetrahedron Lett.1992, 33, 2579] proposed structure of natural plakotenin must be revised. Recently, the total synthesis of plakotenin was achieved via an intramolecular Diels-Alder reaction from a (E,E,Z,E)-tetraene as linear precursor. Using density functional theory, the computation of the four possible transition states for this reaction shows that the previously proposed structure could only have been formed via an energetically high-lying transition state, which is very unlikely. Instead, we suggest that the structure of plakotenin corresponds to the product formed via the lowest transition state. A comparison of experimental and theoretical optical rotation, circular dichroism, and two-dimensional nuclear Overhauser enhancement spectra conclusively proves that the structure of plakotenin is the one that is suggested by the transition state computations. Moreover, the simulation of the nuclear Overhauser enhancement spectra suggests that it is most likely that the misassignment of the (1)H chemical shifts of two methyl groups has led to the wrong structure prediction in the 1992 work. The previously proposed structure of iso-plakotenin remains unaffected by our structure revision, but the structures of homo- and nor-plakotenin must also be revised. The present work shows how the total synthesis of a natural product, together with the theoretical determination of the barrier heights of the reactions involved, can be of great help to assign its structure. It appears that intramolecular Diels-Alder reactions can be modeled accurately by today's first-principles methods of quantum chemistry.

Derivatives and dimers of C50-D5h and C50-D3: a comparison of two closely related but quite differently behaving fullerenes.

A density functional theory study on the reactivity of the energetically most stable C(50) isomers, C(50)-D(5h) and C(50)-D(3), is presented. We explore the reactivity of both fullerenes towards the addition of hydrogen and halogen atoms and towards the formation of dimers. The addition patterns of the derivatives C(50)X(2n) (X = H, F, Cl) that are preferably formed after the saturation of the most reactive sites are investigated as well. The study reveals that while the results for C(50)-D(5h) are in agreement with simple empirical rules, C(50)-D(3) does not show the expected behaviour.

Hydrides and dimers of C(58) fullerenes: structures and stabilities.

A density functional theory (DFT) study of fullerene hydrides C(58)H(2x) (2x = 2,4,...,34) is presented. We consider two relevant isomers, the most stable classical isomer C(58)-C(3v) and the energetically close non-classical isomer C(58)-C(s), which contains a heptagonal ring. Iterative pairwise addition of hydrogen atoms to only the energetically favoured products of the previous iteration yields a set of low energy structures for each composition. From these, low energy pathways are extracted. Analysis of the C-H binding energies along the reaction pathways is performed to identify particularly stable hydride compositions. These are 2x = 6,18,28,34 for C(58)-C(s) and 2x = 10,26,30 for C(58)-C(3v). We therefore suggest that these hydrides are preferably formed in hydrogenation experiments and that it should be possible to distinguish between the two C(58) isomers. We further investigate the dimer formation based on low energy C(58)H(2) addition patterns. All dimers show binding energies of more than 1 eV whereby dispersion interactions play a significant role. Both C(58) isomers can also undergo further aggregation. This leads us to the conclusion that in the absence of other reactant molecules C(58) will form intercage bonds and cannot be isolated in molecular form, which is in accordance with experimental results.

Non-IPR C60 solids.

Films comprising predominantly novel isomers of C(60) [=C(60)(nIPR)] have been generated by low energy ion beam deposition of vibronically excited C(60)(+) onto graphite followed by selective sublimation of C(60)(I(h)) from the deposited isomer mixture. The incident ions were generated by electron impact ionization/fragmentation of sublimed C(70). Images of the C(60)(nIPR) films obtained by applying atomic force microscopy show aggregates, which we attribute to covalently interlinked C(60)(nIPR) units. The covalent bonds are inferred from the significantly higher thermal stability of the C(60)(nIPR) films compared to the C(60)(I(h)) van der Waals solid-as measured by thermal desorption with mass spectrometric detection of the C(60) mass channel (the only desorbable species). In contrast to the characteristic doublet structure of the occupied valence band in the ultraviolet photoelectron spectrum of pure C(60)(I(h)), the valence band of C(60)(nIPR) films exhibits a triplet feature with the additional peak occurring at a binding energy of approximately 2.6 eV. This is an indicator of the electronic modifications induced by intermolecular bonding. C(60)(nIPR) films exhibit a narrower band gap than found for C(60)(I(h)). They also have significantly different chemical reactivity toward incorporation of thermal energy deuterium atoms. In order to model the experimental photoelectron spectra, various covalently linked oligomers of (#1809)C(60)(C(2v)), the second most stable conventional 60-atom fullerene cage, were calculated by means of the density functional theory. These spectral predictions together with analogous previous observations on related fullerene solids such as C(58) lead us to infer that C(60)(nIPR) films consist of fullerene cage isomers containing one or more adjacent pentagon pairs, which mediate covalent cage-cage interconnection.

Low energy hydrogenation products of extended pi systems CnH2x: a density functional theory search strategy, benchmarked against CCSD(T), and applied to C60.

An approach for the systematic determination of particularly stable hydride compositions C(n)H(2x) of a fullerene C(n) is presented. The study is divided into three parts. First, a CCSD(T) benchmark study on benzene and naphthalene hydrogenation is carried out. We show that the TPSS and BP86 functionals give more reliable relative isomer energies and reaction energies than B3LYP, when compared to CCSD(T) calculations. We therefore recommend BP86 for use on fullerenes. In the second part, a scheme for reduction in the immense number of possible fullerene hydride isomers is proposed. The scheme is based on thermodynamic sampling and involves density functional based tight binding as fast preselection method. The testing of the approach for C(60) constitutes the last part of the study. A low energy pathway for C(60)H(36) production is determined. Particularly stable structures are identified through analysis of the reaction energies along this pathway. These are C(60)H(2x) with 2x=18, 30, and 36. The good agreement of these results with the experimental and previous theoretical data suggests that our method is reliable and can be used to study fullerene hydrogenation.

Nucleophilic additions to alkylidene bis(sulfoxides): stereoelectronic effects in vinyl sulfoxides.

Conjugate additions of nucleophiles (e.g. enolates, amines and malonate anions) to bis(p-tolylsulfinyl)alkenes, alkylidene-1,3-dithiane-1,3-dioxides and alkylidene-1,3-dithiolane-1,3-dioxides have recently been published. Reasons for different selectivities and reaction rates will be discussed by consideration of steric and electronic effects. The preferred mode of attack can be explained by stereoelectronic effects (hyperconjugation) in the primarily carbanion, which is stabilized by n-->S-O-sigma* interaction with an antiperiplanar S=O group. Calculation of the transition states [BP86/aug-TZVP] for the addition of acetone enolate to the dithiane-derived alkylidene bis(sulfoxide) revealed that 6.6-7.3 kJ mol(-1) more energy is needed for an attack leading to a less-stabilized carbanion. Two axial S=O groups in dithiolane-derived alkylidene bis(sulfoxides) lead to a higher reactivity towards nucleophiles.

DFT study of fullerene dimers.

Several [2+2] dimerization products of a fullerene Cn (n=50, 52, 54, 56, 58, 60) in its most stable form are presented and discussed. In total, 34 dimers are studied. Only symmetric Cn-Cn dimers (no mixed products) are reported, and only dimers of the fullerenes C50 to C58 with bonds between C atoms in adjacent pentagons are considered. Geometries were optimized within the framework of density functional theory using the Becke-Perdew exchange-correlation functional (BP86) in combination with an empirical dispersive energy correction, which contributes significantly to the binding energy. The results are discussed in the context of the reactivity of adjacent pentagon sites. The lateral interaction between fullerenes is found to be stronger for C50 to C58 than for C60, which is consistent with recent experimental observations. Further, the possibility of polymer formation based on the investigated [2+2] reaction is addressed.