High Charge Delocalization and Conjugation in Oligofuran Molecular Wires

The extent of charge delocalization and of conjugation in oligofurans and oligothiophenes was studied by using mixed valence systems comprising oligofurans and oligothiophenes capped at both ends by ferrocenyl redox units. Using electrochemical, spectral, and computational tools, we find strong charge delocalization in ferrocene‐capped oligofurans which was stronger than in the corresponding oligothiophene systems. Spectroscopic studies suggest that the electronic coupling integral (H_ab) is roughly 30–50 % greater for oligofuran‐bridged systems, indicating better energy matching between ferrocene units and oligofurans. The distance decay constant (damping factor), β, is similar for oligofurans (0.066 A^?1) and oligothiophenes (0.070 A^?1), which suggests a similar extent of delocalization in the bridge, despite the higher HOMO–LUMO gap in oligofurans. Computational studies indicate a slightly larger extent of delocalization in furan‐bridged systems compared with thiophene‐bridged systems, which is consistent with oligofurans being significantly more rigid and less aromatic than oligothiophenes. High charge delocalization in oligofurans, combined with the previously reported strong fluorescence, high mobility, and high rigidity of oligofuran‐based materials makes them attractive candidates for organic electronic applications.     

Chiral Fluorinated α‐Sulfonyl Carbanions: Enantioselective Synthesis and Electrophilic Capture,Racemization Dynamics,and Structure

Enantiomerically pure triflones R¹CH(R²)SO₂CF₃ have been synthesized starting from the corresponding chiral alcohols via thiols and trifluoromethylsulfanes. Key steps of the syntheses of the sulfanes are the photochemical trifluoromethylation of the thiols with CF₃Hal (Hal=halide) or substitution of alkoxyphosphinediamines with CF₃SSCF₃. The deprotonation of RCH(Me)SO₂CF₃ (R=CH₂Ph, iHex) with nBuLi with the formation of salts [RC(Me)? SO₂CF₃]Li and their electrophilic capture both occurred with high enantioselectivities. Displacement of the SO₂CF₃ group of (S)‐MeOCH₂C(Me)(CH₂Ph)SO₂CF₃ (95 % ee) by an ethyl group through the reaction with AlEt₃ gave alkane MeOCH₂C(Me)(CH₂Ph)Et of 96 % ee. Racemization of salts [R¹C(R²)SO₂CF₃]Li follows first‐order kinetics and is mainly an enthalpic process with small negative activation entropy as revealed by polarimetry and dynamic NMR (DNMR) spectroscopy. This is in accordance with a C_α? S bond rotation as the rate‐determining step. Lithium α‐(S)‐trifluoromethyl‐ and α‐(S)‐nonafluorobutylsulfonyl carbanion salts have a much higher racemization barrier than the corresponding α‐(S)‐tert‐butylsulfonyl carbanion salts. Whereas [PhCH₂C(Me)SO₂tBu]Li/DMPU (DMPU = dimethylpropylurea) has a half‐life of racemization at ?105 °C of 2.4 h, that of [PhCH₂C(Me)SO₂CF₃]Li at ?78 °C is 30 d. DNMR spectroscopy of amides (PhCH₂)₂NSO₂CF₃ and (PhCH₂)N(Ph)SO₂CF₃ gave N? S rotational barriers that seem to be distinctly higher than those of nonfluorinated sulfonamides. NMR spectroscopy of [PhCH₂C(Ph)SO₂R]M (M=Li, K, NBu₄; R=CF₃, tBu) shows for both salts a confinement of the negative charge mainly to the C_α atom and a significant benzylic stabilization that is weaker in the trifluoromethylsulfonyl carbanion. According to crystal structure analyses, the carbanions of salts {[PhCH₂C(Ph)SO₂CF₃]Li? L }₂ ( L =2 THF, tetramethylethylenediamine (TMEDA)) and [PhCH₂C(Ph)SO₂CF₃]NBu₄ have the typical chiral C_α? S conformation of α‐sulfonyl carbanions, planar C_α atoms, and short C_α? S bonds. Ab initio calculations of [MeC(Ph)SO₂tBu]^? and [MeC(Ph)SO₂CF₃]^? showed for the fluorinated carbanion stronger n_C→σ* and n_O→σ* interactions and a weaker benzylic stabilization. According to natural bond orbital (NBO) calculations of [R¹C(R²)SO₂R]^? (R=tBu, CF₃) the n_C→σ*_{S? R} interaction is much stronger for R=CF₃. Ab initio calculations gave for [MeC(Ph)SO₂tBu]Li ? 2 Me₂O an O,Li,C_α contact ion pair (CIP) and for [MeC(Ph)SO₂CF₃]Li ? 2 Me₂O an O,Li,O CIP. According to cryoscopy, [PhCH₂C(Ph)SO₂CF₃]Li, [iHexC(Me)SO₂CF₃]Li, and [PhCH₂C(Ph)SO₂CF₃]NBu₄ predominantly form monomers in tetrahydrofuran (THF) at ?108 °C. The NMR spectroscopic data of salts [R¹(R²)SO₂R³]Li (R³=tBu, CF₃) indicate that the dominating monomeric CIPs are devoid of C_α? Li bonds.     

Fully Synthetic Self‐Adjuvanting Thioether‐Conjugated Glycopeptide?Lipopeptide Antitumor Vaccines for the Induction of Complement‐Dependent Cytotoxicity against Tumor Cells

Glycopeptides of tumor‐associated mucin MUC1 are promising target structures for the development of antitumor vaccines. Because these endogenous structures were weakly immunogenic, they were coupled to immune‐response‐stimulating T‐cell epitopes and the Pam₃Cys lipopeptide to induce strong immune responses in mice. A new thioether‐ligation method for the synthesis of two‐ and three‐component vaccines that contain MUC1 glycopeptides as the B‐cell epitopes, a T‐cell epitope peptide, and the Pam₃CSK₄ lipopeptide is described. The resulting fully synthetic vaccines were used for the vaccination of mice, either in a liposome with Freund′s adjuvant or in aqueous PBS buffer. The three‐component vaccines that contained the Tetanus Toxoid P2 T‐cell epitope peptide induced strong immune responses, even when administered just in PBS. By activation of the complement‐dependent cytotoxicity (CDC) complex, the antisera induced the killing of tumor cells.     

A Silyliumylidene Cation Stabilized by an Amidinate Ligand and 4‐Dimethylaminopyridine

The synthesis and reactivity of a silyliumylidene cation stabilized by an amidinate ligand and 4‐dimethylaminopyridine (DMAP) are described. The reaction of the amidinate silicon(I) dimer [ L Si:]₂ ( 1 ; L =PhC(NtBu)₂) with one equivalent of N‐trimethylsilyl‐4‐dimethylaminopyridinium triflate [4‐NMe₂C₅H₄NSiMe₃]OTf and two equivalents of DMAP in THF afforded [ L Si(DMAP)]OTf ( 2 ). The ambiphilic character of 2 is demonstrated from its reactivity. Treatment of 2 with 1 in THF afforded the disilylenylsilylium triflate [ L′ ₂( L )Si]OTf ( 3 ; L′ = L Si:) with the displacement of DMAP. The reaction of 2 with [K{HB(iBu)₃}] and elemental sulfur in THF afforded the silylsilylene [ L SiSi(H){(NtBu)₂C(H)Ph}] ( 4 ) and the base‐stabilized silanethionium triflate [ L Si(S)DMAP]OTf ( 5 ), respectively. Compounds 2 , 3 , and 5 have been characterized by X‐ray crystallography.     

Conformational Analysis of the Anti‐obesity Drug Lorcaserin in Water: How To Take Advantage of Long‐Range Residual Dipolar Couplings

The conformational state of 8‐chloro‐1‐methyl‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepine hydrochloride (lorcaserin) in water has been determined on the basis of one‐bond and long‐range C? H residual dipolar coupling (RDC) data along with DFT computations and ³J_HH coupling‐constant analysis. According to this analysis, lorcaserin exists as a conformational equilibrium of two crown‐chair forms, of which the preferred conformation has the methyl group in an equatorial orientation.     

Ultrasound‐Assisted Construction of Halogen‐Bonded Nanosized Cocrystals That Exhibit Thermosensitive Luminescence

Multi‐component organic nanocrystals that are comprised of two or more supramolecular building blocks can be used to extend the design and assembly scope of solid molecular materials. Herein, we report the use of ultrasonication to prepare halogen‐bonded stilbene‐based nano‐cocrystals that exhibit different photoemission properties, including one‐ and two‐phonon emission and fluorescence lifetimes, relative to those of macrodimensional crystals. The structural transformation from nano‐cocrystals into nanocrystals upon heating results in a luminescence red‐shift from greenish blue to yellow. The temperature‐dependent ratiometric luminescence may allow such nano‐cocrystals to be used as fluorescent sensors and thermosensitive materials.     

Artificial Allosteric Receptors

Cooperative effects in the binding of two or more substrates to different binding sites of a receptor that are a result of a conformational change caused by the binding of the first substrate—also referred to as the effector—are called allosteric effects. In biological systems, allosteric regulation is a widely used mechanism to control the function of proteins and enzymes in cellular metabolism. Inspired by this a lot of efforts have been made in supramolecular chemistry to implement this concept into artificial systems to control functions as molecular recognition, signal amplification, or even reactivity and catalysis. This review gives an up‐to‐date overview over the different approaches that have been reported ever since the first examples from the late 1970s/early 1980s. It covers both homo‐ and heterotropic examples and is divided according to the nature of the effector—cationic, anionic, or neutral—effectors and systems that use combinations of those.     

Unusual Structure,Fluxionality, and Reaction Mechanism of Carbonyl Hydrosilylation by Silyl Hydride Complex [(ArN)Mo(H)(SiH2Ph)(PMe3)3]

The reactions of bis(borohydride) complexes [(RN?)Mo(BH₄)₂(PMe₃)₂] ( 4 : R=2,6‐Me₂C₆H₃; 5 : R=2,6‐iPr₂C₆H₃) with hydrosilanes afford new silyl hydride derivatives [(RN?)Mo(H)(SiR′₃)(PMe₃)₃] ( 3 : R=Ar, R′₃=H₂Ph; 8 : R=Ar′, R′₃=H₂Ph; 9 : R=Ar, R′₃=(OEt)₃; 10 : R=Ar, R′₃=HMePh). These compounds can also be conveniently prepared by reacting [(RN?)Mo(H)(Cl)(PMe₃)₃] with one equivalent of LiBH₄ in the presence of a silane. Complex 3 undergoes intramolecular and intermolecular phosphine exchange, as well as exchange between the silyl ligand and the free silane. Kinetic and DFT studies show that the intermolecular phosphine exchange occurs through the predissociation of a PMe₃ group, which, surprisingly, is facilitated by the silane. The intramolecular exchange proceeds through a new non‐Bailar‐twist pathway. The silyl/silane exchange proceeds through an unusual Mo^VI intermediate, [(ArN?)Mo(H)₂(SiH₂Ph)₂(PMe₃)₂] ( 19 ). Complex 3 was found to be the catalyst of a variety of hydrosilylation reactions of carbonyl compounds (aldehydes and ketones) and nitriles, as well as of silane alcoholysis. Stoichiometric mechanistic studies of the hydrosilylation of acetone, supported by DFT calculations, suggest the operation of an unexpected mechanism, in that the silyl ligand of compound 3 plays an unusual role as a spectator ligand. The addition of acetone to compound 3 leads to the formation of [trans‐(ArN)Mo(OiPr)(SiH₂Ph)(PMe₃)₂] ( 18 ). This latter species does not undergo the elimination of a Si? O group (which corresponds to the conventional Ojima′s mechanism of hydrosilylation). Rather, complex 18 undergoes unusual reversible β‐CH activation of the isopropoxy ligand. In the hydrosilylation of benzaldehyde, the reaction proceeds through the formation of a new intermediate bis(benzaldehyde) adduct, [(ArN?)Mo(η²‐PhC(O)H)₂(PMe₃)], which reacts further with hydrosilane through a η¹‐silane complex, as studied by DFT calculations.