Larger Substituents on Amide Cavitands Induce Bigger Cavities.

A series of quinoxaline cavitands bearing pendant amide groups with various substituent sizes (Et, iPr, tBu) were synthesized, and their cavity size/structure were investigated by X-ray and NMR analyses. In the case of the Et or iPr amide cavitand, the conformation of the molecule was in the vase form, while the bulky tBu amide cavitand gave the kite conformation at room temperature. X-ray crystal structures of Et and iPr cavitands clearly showed the intramolecular H-bondings to influence the conformation and the cavity sizes dependent on the bulkiness of functional groups. The 1H NMR spectrum revealed that the Et cavitand can encapsulate an adamantane guest compound with slow exchange.

Unconventional Synthesis of a CuI Rotaxane with a Superacceptor Stopper: Ultrafast Excited-State Dynamics and Near-Infrared Luminescence.

A CuI bis-phenanthroline rotaxane was prepared by using the [2+2] cycloaddition-retroelectrocyclization (CA-RE) reaction to graft a bulky dicyanoquinodimethane (DCNQ) stopper. The electronic properties were investigated with electrochemical and photophysical techniques, in parallel with three reference compounds, namely, the DCNQ derivative alone, the DCNQ-based phenanthroline ligand, and an analogue CuI complex lacking the DCNQ moiety. In all the systems containing the DCNQ unit, the lowest electronic excited states are centered thereon, with the singlet level (S1 ) located at about 1.0 eV, as suggested by TDDFT calculations. Accordingly, in the DCNQ-equipped rotaxane, the typical metal-to-ligand charge-transfer luminescence of the CuI center is totally quenched. Ultrafast transient absorption and emission studies show that, in the rotaxane, the final sink of photoinduced processes is the lowest singlet state of the DCNQ moiety (S1 ), which exhibits strong charge-transfer character and a lifetime of 0.4 ps. Its deactivation leads to population of another excited state with a lifetime of 1.3 ps, which can be the related triplet state (T1 ) or a vibrationally hot level (hot-S0 ). Notably, S1 also shows stimulated fluorescence in the near-infrared (NIR) region between 1100 and 1500 nm, corroborating the TDDFT prediction. This unusual finding opens up the study of ultrashort-lived NIR luminescence in organic donor-acceptor systems.

Adsorbate-Induced Modification of the Confining Barriers in a Quantum Box Array.

Quantum devices depend on addressable elements, which can be modified separately and in their mutual interaction. Self-assembly at surfaces, for example, formation of a porous (metal-) organic network, provides an ideal way to manufacture arrays of identical quantum boxes, arising in this case from the confinement of the electronic (Shockley) surface state within the pores. We show that the electronic quantum box state as well as the interbox coupling can be modified locally to a varying extent by a selective choice of adsorbates, here C60, interacting with the barrier. In view of the wealth of differently acting adsorbates, this approach allows for engineering quantum states in on-surface network architectures.

Systematic Investigation of Resorcin[4]arene-Based Cavitands as Affinity Materials on Quartz Crystal Microbalances.

Resorcin[4]arene cavitands are well-known supramolecular hosts, and their outstanding guest-binding abilities in solution have been studied in detail in recent decades. In a systematic approach, different resorcin[4]arene cavitands and container molecules are characterized as affinity materials for gravimetric sensing using high-fundamental-frequency quartz crystal microbalances. Analysis of their affinity toward a series of various analytes reveals a remarkable dependence of both selectivity and sensitivity on the shape, accessibility, and size of the cavity, along with their supramolecular interactions with the host molecules.

Structural and Conformational Aspects of Equatorial and Axial Trifluoromethyl, Difluoromethyl, and Monofluoromethyl Groups.

The X-ray crystal structures of cis- and trans-1-(indol-3-yl)-4-methyl cyclohexane and its congeners with stepwise fluorination of the methyl group are reported. The trans-configured compounds adopted diequatorial conformations, whereas the cis analogues adopted regular cyclohexane chair conformations with the methyl group preferentially assuming the axial position, even in the case of the CF3 group. Surprisingly, although the axial CF3 derivative displayed distinct valence deformations in the cyclohexane moiety, the observed structural changes were relatively modest. The cis derivatives with axial mono- and difluorinated methyl groups exhibited conformational disorder in the crystals with significant population levels for the staggered conformations that had one fluorine atom in the endo position; their respective trans counterparts adopted unique conformations, but again with one fluorine atom in the endo position. Theoretical calculations for a series of cis- and trans-1,4-dimethyl cyclohexane model compounds with stepwise fluorination of one equatorial or axial methyl group reproduced the experimentally observed structural response patterns very well, reproduced the experimentally determined nonlinear correlation of the axial-equatorial energy difference with the degree of methyl fluorination in a satisfactory manner, and provided further insights into important conformational aspects of partially fluorinated methyl groups.

Design and Synthesis of Aviram-Ratner-Type Dyads and Rectification Studies in Langmuir-Blodgett (LB) Films.

The design and synthesis of Aviram-Ratner-type molecular rectifiers, featuring an anilino-substituted extended tetracyanoquinodimethane (exTCNQ) acceptor, covalently linked by the σ-spacer bicyclo[2.2.2]octane (BCO) to a tetrathiafulvalene (TTF) donor moiety, are described. The rigid BCO spacer keeps the TTF donor and exTCNQ acceptor moieties apart, as demonstrated by X-ray analysis. The photophysical properties of the TTF-BCO-exTCNQ dyads were investigated by UV/Vis and EPR spectroscopy, electrochemical studies, and theoretical calculations. Langmuir-Blodgett films were prepared and used in the fabrication and electrical studies of junction devices. One dyad showed the asymmetric current-voltage (I-V) curve characteristic for rectification, unlike control compounds containing the TTF unit but not the exTCNQ moiety or comprising the exTCNQ acceptor moiety but lacking the donor TTF part, which both gave symmetric I-V curves. The direction of the observed rectification indicated that the preferred electron current flows from the exTCNQ acceptor to the TTF donor.

Fluorine Scan of Inhibitors of the Cysteine Protease Human Cathepsin†L: Dipolar and Quadrupolar Effects in the π-Stacking of Fluorinated Phenyl Rings on Peptide Amide Bonds.

The π-stacking of fluorinated benzene rings on protein backbone amide groups was investigated, using a dual approach comprising enzyme-ligand binding studies complemented by high-level quantum chemical calculations. In the experimental study, the phenyl substituent of triazine nitrile inhibitors of human cathepsin L (hCatL), which stacks onto the peptide amide bond Gly67-Gly68 at the entrance of the S3 pocket, was systematically fluorinated, and differences in inhibitory potency were measured in a fluorimetric assay. Binding affinity is influenced by lipophilicity (clog P), the dipole and quadrupole moments of the fluorinated rings, but also by additional interactions of the introduced fluorine atoms with the local environment of the pocket. Generally, the higher the degree of fluorination, the better the binding affinities. Gas phase calculations strongly support the contributions of the molecular quadrupole moments of the fluorinated phenyl rings to the π-stacking interaction with the peptide bond. These findings provide useful guidelines for enhancing π-stacking on protein amide fragments.

Aromatic Interactions in Organocatalyst Design: Augmenting Selectivity Reversal in Iminium Ion Activation.

Invited for the cover of this issue is the group of Ryan Gilmour at the Westfälische Wilhelms-Universität Münster. The image depicts how the modes of stereoinduction differ for- N-methylpyrrole to- N-methylindole. Read the full text of the article at 10.1002/chem.201500270.

Aromatic Interactions in Organocatalyst Design: Augmenting Selectivity Reversal in Iminium Ion Activation.

Substituting N-methylpyrrole for N-methyindole in secondary-amine-catalysed Friedel-Crafts reactions leads to a curious erosion of enantioselectivity. In extreme cases, this substrate dependence can lead to an inversion in the sense of enantioinduction. Indeed, these closely similar transformations require two structurally distinct catalysts to obtain comparable selectivities. Herein a focussed molecular editing study is disclosed to illuminate the structural features responsible for this disparity, and thus identify lead catalyst structures to further exploit this selectivity reversal. Key to effective catalyst re-engineering was delineating the non-covalent interactions that manifest themselves in conformation. Herein we disclose preliminary validation that intermolecular aromatic (CH-π and cation-π) interactions between the incipient iminium cation and the indole ring system is key to rationalising selectivity reversal. This is absent in the N-methylpyrrole alkylation, thus forming the basis of two competing enantio-induction pathways. A simple L-valine catalyst has been developed that significantly augments this interaction.

The 6,6-dicyanopentafulvene core: a template for the design of electron-acceptor compounds.

The electron-accepting ability of 6,6-dicyanopentafulvenes (DCFs) can be varied extensively through substitution on the five-membered ring. The reduction potentials for a set of 2,3,4,5-tetraphenyl-substituted DCFs, with varying substituents at the para-position of the phenyl rings, strongly correlate with their Hammett σp-parameters. By combining cyclic voltammetry with DFT calculations ((U)B3LYP/6-311+G(d)), using the conductor-like polarizable continuum model (CPCM) for implicit solvation, the absolute reduction potentials of a set of twenty DCFs were reproduced with a mean absolute deviation of 0.10 eV and a maximum deviation of 0.19 eV. Our experimentally investigated DCFs have reduction potentials within 3.67-4.41 eV, however, the computations reveal that DCFs with experimental reduction potentials as high as 5.3 eV could be achieved, higher than that of F4-TCNQ (5.02 eV). Thus, the DCF core is a template that allows variation in the reduction potentials by about 1.6 eV.

Push-Pull Buta-1,2,3-trienes: exceptionally low rotational barriers of cumulenic C=C bonds and proacetylenic reactivity.

A variety of asymmetrically donor-acceptor-substituted [3]cumulenes (buta-1,2,3-trienes) were synthesized by developed procedures. The activation barriers to rotation ΔG(≠) were measured by variable temperature NMR spectroscopy and found to be as low as 11.8 kcal mol(-1) , in the range of the barriers for rotation around sterically hindered single bonds. The central C=C bond of the push-pull-substituted [3]cumulene moiety is shortened down to 1.22 Šas measured by X-ray crystallography, leading to a substantial bond length alternation (BLA) of up to 0.17 Å. All the experimental results are supported by DFT calculations. Zwitterionic transition states (TS) of bond rotation confirm the postulated proacetylenic character of donor-acceptor [3]cumulenes. Additional support for the proacetylenic character of these chromophores is provided by their reaction with tetracyanoethene (TCNE) in a cycloaddition-retroelectrocyclization (CA-RE) cascade characteristic of donor-polarized acetylenes.

Strain-accelerated formation of chiral, optically active buta-1,3-dienes.

The formal [2+2] cycloaddition-retroelectrocyclization (CA-RE) reactions between tetracyanoethylene (TCNE) and strained, electron-rich dibenzo-fused cyclooctynes were studied. The effect of ring strain on the reaction kinetics was quantified, revealing that the rates of cycloaddition using strained, cyclic alkynes are up to 5500 times greater at 298 K than those of reactions using unstrained alkynes. Cyclobutene reaction intermediates, as well as buta-1,3-diene products, were isolated and their structures were studied crystallographically. Isolation of a rare example of a chiral buta-1,3-diene that is optically active and configurationally stable at room temperature is reported. Computational studies on the enantiomerization pathway of the buta-1,3-diene products showed that the eight-membered ring inverts via a boat conformer in a ring-flip mechanism. In agreement with computed values, experimentally measured activation barriers of racemization in these compounds were found to be up to 26 kcal mol(-1) .

Synthesis and optoelectronic properties of Janus-dendrimer-type multivalent donor-acceptor systems.

A convergent, multistep protocol was employed for the synthesis of a Janus-type multivalent donor-acceptor system. The synthetic approach is based on a Sonogashira cross-coupling of two differently ferrocene-(Fc) substituted dendrons and a final sixfold [2 + 2] cycloaddition-retroelectrocyclization (CA-RE) reaction with tetracyanoethene, which occurs regioselectively at only one of the rigidly linked dendrons. The structural and optoelectronic properties of the compounds were investigated by X-ray analysis, UV/vis spectroscopy, and electrochemistry. The target Janus-system displays redox-amphoteric behavior. The nonalkynylated Fc end groups in one dendron are readily and reversibly oxidized. The second dendron, in which the terminal Fc-activated alkynes underwent the CA-RE reaction to give tetracyanobuta-1,3-dienes in the final step of the synthesis, undergoes four reversible 3-e(-) reductions in the very narrow potential range of 1 V. A spontaneous intramolecular charge transfer from the donor into the acceptor hemisphere was not observed. Furthermore, the oxidation potential of the Fc donors in one hemisphere is hardly perturbed by the push-pull acceptors in the other, which suggests that electronic communication along the π-system, with several meta-connectivities, is not efficient. Therefore, the charge-transfer bands seen in the Janus-type system originate from the interaction of the Fc donors with the directly connected tetracyanobuta-1,3-diene acceptors in the same hemisphere.

Replacement of water molecules in a phosphate binding site by furanoside-appended lin-benzoguanine ligands of tRNA-guanine transglycosylase (TGT).

The enzyme tRNA-guanine transglycosylase has been identified as a drug target for the foodborne illness shigellosis. A key challenge in structure-based design for this enzyme is the filling of the polar ribose-34 pocket. Herein, we describe a novel series of ligands consisting of furanoside-appended lin-benzoguanines. They were designed to replace a conserved water cluster and differ by the functional groups at C(2) and C(3) of the furanosyl moiety being either OH or OMe. The unfavorable desolvation of Asp102 and Asp280, which are located close to the ribose-34 pocket, had a significant impact on binding affinity. While the enzyme has tRNA as its natural substrate, X-ray co-crystal structures revealed that the furanosyl moieties of the ligands are not accommodated in the tRNA ribose-34 site, but at the location of the adjacent phosphate group. A remarkable similarity of the position of the oxygen atoms in these two structures suggests furanosides as a potential phosphate isoster.

Structures and properties of molecular torsion balances to decipher the nature of substituent effects on the aromatic edge-to-face interaction.

Various recent computational studies initiated this systematic re-investigation of substituent effects on aromatic edge-to-face interactions. Five series of Tröger base derived molecular torsion balances (MTBs), initially introduced by Wilcox and co-workers, showing an aromatic edge-to-face interaction in the folded, but not in the unfolded form, were synthesized. A fluorine atom or a trifluoromethyl group was introduced onto the edge ring in ortho-, meta-, and para-positions to the C-H group interacting with the face component. The substituents on the face component were varied from electron-donating to electron-withdrawing. Extensive X-ray crystallographic data allowed for a discussion on the conformational behavior of the torsional balances in the solid state. While most systems adopt the folded conformation, some were found to form supramolecular intercalative dimers, lacking the intramolecular edge-to-face interaction, which is compensated by the gain of aromatic π-stacking interactions between four aryl rings of the two molecular components. This dimerization does not take place in solution. The folding free enthalpy ΔG(fold) of all torsion balances was determined by (1)H NMR measurements by using 10 mM solutions of samples in CDCl3 and C6D6. Only the ΔG(fold) values of balances bearing an edge-ring substituent in ortho-position to the interacting C-H show a steep linear correlation with the Hammett parameter (σ(meta)) of the face-component substituent. Thermodynamic analysis using van't Hoff plots revealed that the interaction is enthalpy-driven. The ΔG(fold) values of the balances, in addition to partial charge calculations, suggest that increasing the polarization of the interacting C-H group makes a favorable contribution to the edge-to-face interaction. The largest contribution, however, seems to originate from local direct interactions between the substituent in ortho-position to the edge-ring C-H and the substituted face ring.

C60 pyrrolidine bis-carboxylic acid derivative as a versatile precursor for biocompatible fullerenes.

A C60 Prato derivative with bis-(t)Bu ester was prepared as a stable and convenient scaffold for the development of fullerene derivatives such as water-soluble C60-PEG conjugates, fulleropeptides via solid phase synthesis, and bis-functionalized C60.

Evaluation of hydrogen-bond acceptors for redox-switchable resorcin[4]arene cavitands.

Various H-bond acceptor groups were evaluated for their propensity to induce conformational switching between the kite and vase forms of diquinone-diquinoxaline resorcin[4]arene cavitands upon redox interconversion. The H-bond acceptors were placed on the quinoxaline walls with the purpose of stabilizing the vase form only in the reduced hydroquinone state of the cavitand by forming H-bonds with the hydroquinone OH groups. Design guidelines for successful acceptors were derived. The carboxamide acceptor was shown to be the best candidate. Based on this moiety, a redox-switchable triptycene-based basket that can completely sterically encapsulate a guest in its closed vase conformation was prepared. The basket binds small molecule guests with association constants of up to 10(4) M(-1) in mesitylene-d12 and exhibits slow guest exchange kinetics with a half-life for guest release in the order of 10(4) s.

Experimental and computational study of BODIPY dye-labeled cavitand dynamics.

Understanding the distance distribution and dynamics between moieties attached to the walls of a resorcin[4]arene cavitand, which is switchable between an expanded kite and a contracted vase form, might enable the use of this molecular system for the study of fundamental distance-dependent interactions. Toward this goal, a combined experimental and molecular dynamics (MD) simulation study on donor/acceptor borondipyrromethene (BODIPY) dye-labeled cavitands present in the vase and kite forms was performed. Direct comparison between anisotropy decays calculated from MD simulations with experimental fluorescence anisotropy data showed excellent agreement, indicating that the simulations provide an accurate representation of the dynamics of the system. Distance distributions between the BODIPY dyes were established by comparing time-resolved Förster resonance energy transfer experiments and MD simulations. Fluorescence intensity decay curves emulated on the basis of the MD trajectories showed good agreement with the experimental data, suggesting that the simulations present an accurate picture of the distance distributions and dynamics in this molecular system and provide an important tool for understanding the behavior of extended molecular systems and designing future applications.

From homoconjugated push-pull chromophores to donor-acceptor-substituted spiro systems by thermal rearrangement.

Series of homoconjugated push-pull chromophores and donor-acceptor (D-A)-functionalized spiro compounds were synthesized, in which the electron-donating strength of the anilino donor groups was systematically varied. The structural and optoelectronic properties of the compounds were investigated by X-ray analysis, UV/Vis spectroscopy, electrochemistry, and computational analysis. The homoconjugated push-pull chromophores with a central bicyclo[4.2.0]octane scaffold were obtained in high yield by [2+2] cycloaddition of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) to N,N-dialkylanilino- or N,N-diarylanilino-substituted activated alkynes. The spirocyclic compounds were formed by thermal rearrangement of the homoconjugated adducts. They also can be prepared in a one-pot reaction starting from DDQ and anilino-substituted alkynes. Spiro products with N,N-diphenylanilino and N,N-diisopropylanilino groups were isolated in high yields whereas compounds with pyrrolidino, didodecylamino, and dimethylamino substituents gave poor yields, with formation of insoluble side products. It was shown by in situ trapping experiments with TCNE that cycloreversion is possible during the thermal rearrangement, thereby liberating DDQ. In the low-yielding transformations, DDQ oxidizes the anilino species present, presumably via an intermediate iminium ion pathway. Such a pathway is not available for the N,N-diphenylanilino derivative and, in the case of the N,N-diisopropylanilino derivative, would generate a strained iminium ion (A1,3 strain). The mechanism of the thermal rearrangement was investigated by EPR spectroscopy, which provides good evidence for a proposed biradical pathway starting with the homolytic cleavage of the most strained (CN)C-C(CN) bond between the fused four- and six-membered rings in the homoconjugated adducts.

Cyanobuta-1,3-dienes as novel electron acceptors for photoactive multicomponent systems.

The synthesis, electrochemical, and photophysical properties of five multicomponent systems featuring a Zn(II) porphyrin (ZnP) linked to one or two anilino donor-substituted pentacyano- (PCBD) or tetracyanobuta-1,3-dienes (TCBD), with and without an interchromophoric bridging spacer (S), are reported: ZnP-S-PCBD (1), ZnP-S-TCBD (2), ZnP-TCBD (3), ZnP-(S-PCBD)2 (4), and ZnP-(S-TCBD)2 (5). By means of steady-state and time-resolved absorption and luminescence spectroscopy (RT and 77 K), photoinduced intramolecular energy and electron transfer processes are evidenced, upon excitation of the porphyrin unit. In systems equipped with the strongest acceptor PCBD and the spacer (1, 4), no evidence of electron transfer is found in toluene, suggesting ZnP→PCBD energy transfer, followed by ultrafast (<10 ps) intrinsic deactivation of the PCBD moiety. In the analogous systems with the weaker acceptor TCBD (2, 5), photoinduced electron transfer occurs in benzonitrile, generating a charge-separated (CS) state lasting 2.3 µs. Such a long lifetime, in light of the high Gibbs free energy for charge recombination (ΔG(CR)=-1.39 eV), suggests a back-electron transfer process occurring in the so-called Marcus inverted region. Notably, in system 3 lacking the interchromophoric spacer, photoinduced charge separation followed by charge recombination occur within 20 ps. This is a consequence of the close vicinity of the donor-acceptor partners and of a virtually activationless electron transfer process. These results indicate that the strongly electron-accepting cyanobuta-1,3-dienes might become promising alternatives to quinone-, perylenediimide-, and fullerene-derived acceptors in multicomponent modules featuring photoinduced electron transfer.