Lanthanide(III) Complexes of Cyclen Triacetates and Triamides Bearing Tertiary Amide-Linked Antennae

The coordination compounds of the trivalent lanthanide ions (Ln(III)) have unique photophysical properties. Ln(III) excitation is usually performed through a light-harvesting antenna. To enable Ln(III)-based emitters to reach their full potential, an understanding of how complex structure affects sensitization and quenching processes is necessary. Here, the role of the linker between the antenna and the metal binding fragment was studied. Four macrocyclic ligands carrying coumarin 2 or 4-methoxymethylcarbostyril sensitizing antennae linked to an octadentate macrocyclic ligand binding site were synthesized. Complexation with Ln(III) (Ln = La, Sm, Eu, Gd, Tb, Yb and Lu) yielded species with overall −1, 0, or +2 and +3-charge. Paramagnetic ¹H NMR spectroscopy indicated subtle differences between the coumarin- and carbostyril-carrying Eu(III) and Yb(III) complexes. Cyclic voltammetry showed that the effect of the linker on the Eu(III)/Eu(II) apparent reduction potential was dependent on the electronic properties of the N-substituent. The Eu(III), Tb(III) and Sm(III) complexes were all luminescent. Coumarin-sensitized complexes were poorly emissive; photoinduced electron transfer was not a major quenching pathway in these species. These results show that seemingly similar emitters can undergo very different photophysical processes, and highlight the crucial role the linker can play.     

Pinus sylvestris L. and Syzygium aromaticum (L.) Merr. & L. M. Perry Essential Oils Inhibit Endotoxin-Induced Airway Hyperreactivity despite Aggravated Inflammatory Mechanisms in Mice

Scots pine (SO) and clove (CO) essential oils (EOs) are commonly used by inhalation, and their main components are shown to reduce inflammatory mediator production. The aim of our research was to investigate the chemical composition of commercially available SO and CO by gas chromatography–mass spectrometry and study their effects on airway functions and inflammation in an acute pneumonitis mouse model. Inflammation was evoked by intratracheal endotoxin and EOs were inhaled three times during the 24 h experimental period. Respiratory function was analyzed by unrestrained whole-body plethysmography, lung inflammation by semiquantitative histopathological scoring, myeloperoxidase (MPO) activity and cytokine measurements. α-Pinene (39.4%) was the main component in SO, and eugenol (88.6%) in CO. Both SO and CO significantly reduced airway hyperresponsiveness, and prevented peak expiratory flow, tidal volume increases and perivascular edema formation. Meanwhile, inflammatory cell infiltration was not remarkably affected. In contrast, MPO activity and several inflammatory cytokines (IL-1β, KC, MCP-1, MIP-2, TNF-α) were aggravated by both EOs. This is the first evidence that SO and CO inhalation improve airway function, but enhance certain inflammatory parameters. These results suggest that these EOs should be used with caution in cases of inflammation-associated respiratory diseases.     

Synthetic Route to Ergot Alkaloids

Rye is sometimes infected by a fungus called Claviceps purpurea. The term ergot designates the dark, brown, tuberous bodies which can be collected before or during harvesting and represent one of the most remarkable drugs of our therapeutic arsenal. Actually, the most significant alkaloids are metabolic products of these fungi. We elaborated three alternative total synthetic pathways to construct the ergoline skeleton, one of which – suitable for scaling up – finally resulted in (+)‐lysergic acid ( 32a ) and α‐ergocryptine ( 1 ) (Schemes 5 and 6).     

Toward less dependence on platinum group metal catalysts: the merits of utilizing tin

Minute stoichiometric bimetallic clusters rich in tin (PtSn 2, RhSn 2, and RuSn 2) are powerful selective hydrogenation catalysts: these "molecular metallic" entities, supported on mesoporous silica and characterized by aberration-corrected electron microscopy, yield high percentages of cyclododecene (CDE) at fractional conversions ranging from 0.45 to 0.70 of the parent cyclododecatriene (CDT) at modest temperatures and under solvent-free conditions.     

A compact water-soluble porphyrin bearing an iodoacetamido bioconjugatable site

A broad range of applications requires access to porphyrins that are compact, water-soluble, and bioconjugatable. A symmetrically branched hydrocarbon chain ('swallowtail') bearing polar end groups imparts high (>10 mM) aqueous solubility upon incorporation at one of the meso positions of a trans-AB-porphyrin. Two such swallowtail-porphyrins (1a, 1b) equipped with a conjugatable group (carboxylic acid, bromophenyl) have been prepared previously. The synthesis of three new water-soluble trans-AB-porphyrins is reported, where each porphyrin bears a diphosphonate-terminated swallowtail group and an amino (2a), acetamido (2b), or iodoacetamido (2c) group. The amine affords considerable versatility for functionalization. The iodoacetamide provides a sulfhydryl-reactive site for bioconjugation. Porphyrins were fully characterized in aqueous solution by 1H NMR spectroscopy (in D2O), ESI-MS, static absorption spectroscopy, and static and time-resolved fluorescence spectroscopy. Porphyrins 2a-2c exhibit characteristic porphyrin absorption and emission bands in aqueous solution, with a strong, sharp absorption band in the blue region (approximately 401 nm) and emission in the red region (approximately 624, 686 nm). Porphyrin 2b in aqueous phosphate buffer or phosphate-buffered saline solution exhibits a fluorescence quantum yield of approximately 0.04 and an excited singlet-state lifetime of approximately 11 ns. Collectively, the facile synthesis, amenability to bioconjugation, large spacing between the main absorption and fluorescence features, and long singlet excited-state lifetime make this molecular design quite attractive for a range of biomedical applications.     

Cobalt-Catalyzed Enantioselective Hydrogenation of Trisubstituted Carbocyclic Olefins: An Access to Chiral Cyclic Amides

The enantioselective hydrogenation of cyclic enamides has been achieved using an earth-abundant cobalt-bisphosphine catalyst. Using CoCl₂/(S,S)-Ph-BPE, several trisubstituted carbocyclic enamides were reduced with high activity and excellent enantioselectivity (up to 99 %) to the corresponding saturated amides. The methodology can be extended to the synthesis of chiral amines by base hydrolysis of the hydrogenation products. Preliminary mechanistic investigations reveal the presence of a high spin cobalt (II) species in the catalytic cycle. We propose that the hydrogenation of the carbon-carbon double bond proceeds via a sigma-bond-metathesis pathway.     

Molecular structures of the two most stable conformers of free glycine

The equilibrium molecular structures of the two lowest-energy conformers of glycine, Gly-Ip and Gly-IIn, have been characterized by high-level ab initio electronic structure computations, including all-electron cc-pVTZ CCSD(T) geometry optimizations and 6-31G* MP2 quartic force fields, the latter to account for anharmonic zero-point vibrational effects to isotopologic rotational constants. Based on experimentally measured vibrationally averaged effective rotational constant sets of several isotopologues and our ab initio data for structural constraints and zero-point vibrational shifts, least-squares structural refinements were performed to determine improved Born-Oppenheimer equilibrium (r(e)) structures of Gly-Ip and Gly-IIn. Without the ab initio constraints even the extensive set of empirical rotational constants available for 5 and 10 isotopologues of Gly-Ip and Gly-IIn, respectively, cannot satisfactorily fix their molecular structure. Excellent agreement between theory and experiment is found for the rotational constants of both conformers, the rms residual of the final fits being 7.8 and 51.6 kHz for Gly-Ip and Gly-IIn, respectively. High-level ab initio computations with focal point extrapolations determine the barrier to planarity separating Gly-IIp and Gly-IIn to be 20.5 +/- 5.0 cm(-1). The equilibrium torsion angle tau(NCCO) of Gly-IIn, characterizing the deviation of its heavy-atom framework from planarity, is (11 +/- 2) degrees. Nevertheless, in the ground vibrational state the effective structure of Gly-IIn has a plane of symmetry.     

Thermoascus aurantiacus CBHI/Cel7A production in Trichoderma reesei on alternative carbon sources

To develop functional enzymes in cellulose hydrolysis at or above 70 degrees C the cellobiohydrolase (CBHI/Cel7A) of Thermoascus aurantiacus was cloned and expressed in Trichoderma reesei Rut-C30 under the strong cbh1 promoter. Cellulase production of the parental strain and the novel strain (RF6026) was examined in submerged fermentation experiments using various carbon sources, which were lactose, Solka Floc 200 cellulose powder, and steam pretreated corn stover. An industrially feasible production medium was used containing only distiller's spent grain, KH(2)PO(4), and (NH(4))(2)SO(4). Enzyme production was followed by measurements of protein concentration, total cellulase enzyme activity (filter paper activity), beta-glucosidase activity, CBHI activity, and endogenase I (EGI) activity. The Thermoascus CBHI/Cel7A activity was taken as an indication of the heterologous gene expression under the cbh1 promoter.     

Secondary structures of peptides and proteins via NMR chemical-shielding anisotropy (CSA) parameters

Complete nuclear magnetic resonance (NMR) chemical-shielding tensors, sigma, have been computed at different levels of density-functional theory (DFT), within the gauge-including atomic orbital (GIAO) formalism, for the atoms of the peptide model For-L-Ala-NH2 as a function of the backbone dihedral angles phi and psi by employing a dense grid of 10 degrees. A complete set of rigorously orthogonal symmetric tensor invariants, {sigma iso, rho, tau}, is introduced, where sigma iso is the usual isotropic chemical shielding, while the newly introduced rho and tau parameters describe the magnitude and the orientation/shape of the chemical-shielding anisotropy (CSA), respectively. The set {sigma iso, rho, tau} is unaffected by unitary transformations of the symmetric part of the shielding tensor. The mathematically and physically motivated {rho, tau} anisotropy pair is easily connected to more traditional shielding anisotropy measures, like span (Omega) and skew (kappa). The effectiveness of the different partitions of the CSA information in predicting conformations of peptides and proteins has been tested throughout the Ramachandran space by generating theoretical NMR anisotropy surfaces for our For-L-Ala-NH2 model. The CSA surfaces, including Omega(phi, psi), kappa(phi, psi), rho(phi, psi), and tau(phi, psi) are highly structured. Individually, none of these surfaces is able to distinguish unequivocally between the alpha-helix and beta-strand secondary structural types of proteins. However, two- and three-dimensional correlated plots, including Omega versus kappa, rho versus tau, and sigma iso versus rho versus tau, especially for 13Calpha, have considerable promise in distinguishing among all four of the major secondary structural elements.     

Intramolecular Hydrogen Bonding Restricts Gd–Aqua-Ligand Dynamics

Aqua ligands can undergo rapid internal rotation about the M−O bond. For magnetic resonance contrast agents, this rotation results in diminished relaxivity. Herein, we show that an intramolecular hydrogen bond to the aqua ligand can reduce this internal rotation and increase relaxivity. Molecular modeling was used to design a series of four Gd complexes capable of forming an intramolecular H-bond to the coordinated water ligand, and these complexes had anomalously high relaxivities compared to similar complexes lacking a H-bond acceptor. Molecular dynamics simulations supported the formation of a stable intramolecular H-bond, while alternative hypotheses that could explain the higher relaxivity were systematically ruled out. Intramolecular H-bonding represents a useful strategy to limit internal water rotational motion and increase relaxivity of Gd complexes.