Ethyl 1-benzyl-1,2,3,3a,4,10b-hexa-hydro-pyrrolo-[2',3':3,4]pyrrolo-[1,2-a]benzimidazole-2-carboxyl-ate.

The title mol-ecule, C(22)H(23)N(3)O(2), was obtained via an intra-molecular cyclo-addition of an azomethine ylide and an alkene tethered by a benzimidazole unit. The benzoimidazole unit is essentially planar, with an r.m.s. deviation of 0.0087 Å from the nine constituent atoms. It has a cis fusion of the two pyrrolidine rings as well as a cis ester appendage. The two pyrrolidine rings rings have envelope conformations. The crystal packing is stabilized by aromatic π-π stacking of parallel benzimidazole ring systems, with a centroid-to-centroid distance of 3.518 (6) Å. Weak inter-molecular C-H⋯O contacts may also play a role in the stability of the packing

The Trials and Tribulations of Structure Assisted Design of KCa Channel Activators.

Calcium-activated K+ channels constitute attractive targets for the treatment of neurological and cardiovascular diseases. To explain why certain 2-aminobenzothiazole/oxazole-type KCa activators (SKAs) are KCa3.1 selective we previously generated homology models of the C-terminal calmodulin-binding domain (CaM-BD) of KCa3.1 and KCa2.3 in complex with CaM using Rosetta modeling software. We here attempted to employ this atomistic level understanding of KCa activator binding to switch selectivity around and design KCa2.2 selective activators as potential anticonvulsants. In this structure-based drug design approach we used RosettaLigand docking and carefully compared the binding poses of various SKA compounds in the KCa2.2 and KCa3.1 CaM-BD/CaM interface pocket. Based on differences between residues in the KCa2.2 and KCa.3.1 models we virtually designed 168 new SKA compounds. The compounds that were predicted to be both potent and KCa2.2 selective were synthesized, and their activity and selectivity tested by manual or automated electrophysiology. However, we failed to identify any KCa2.2 selective compounds. Based on the full-length KCa3.1 structure it was recently demonstrated that the C-terminal crystal dimer was an artefact and suggested that the "real" binding pocket for the KCa activators is located at the S4-S5 linker. We here confirmed this structural hypothesis through mutagenesis and now offer a new, corrected binding site model for the SKA-type KCa channel activators. SKA-111 (5-methylnaphtho[1,2-d]thiazol-2-amine) is binding in the interface between the CaM N-lobe and the S4-S5 linker where it makes van der Waals contacts with S181 and L185 in the S45A helix of KCa3.1

The Unusual Structural Behavior of Heteroleptic Aryl Copper(I) Thiolato Molecules : Cis vs Trans Structures and London Dispersion Effects

A series of heteroleptic aryl copper(I) thiolato complexes of formula {Cu2(SAr)Mes}2 (Ar = C6H3-2,6-(C6H2-2,4,6-Me3)2 (ArMe6), 1; C6H3-2,6-(C6H3-2,6-iPr2)2 (AriPr4), 2; C6H3-2,6-(C6H2-2,4,6-iPr3)2 (AriPr6), 3) and {Cu4(SAr)Mes3} (Ar = C6H-2,6-(C6H2-2,4,6-iPr3)2-3,5-iPr2 (AriPr8), 4) were synthesized by the reactions of the corresponding bulky terphenyl thiols with mesitylcopper(I) with elimination of mesitylene. All complexes were characterized by single crystal X-ray diffraction analysis and spectroscopy (NMR, infrared, and UV-vis). The data for 1-3 revealed tetrametallic Cu4 core structures in which two thiolato or two mesityl ligands bridge the metals. Although 1 and 2 feature the expected conventional alternating thiolato and mesityl bridging patterns, 3 has a previously unknown structural arrangement in which the two thiolato ligands are adjacent to each other. Since complex 3 has a more crowding aryl group on the thiolato ligands, the cis arrangement of the ligands in 3 is sterically counterintuitive and is likely due to London dispersion (LD) energy effects. Complex 4 also has an unusual structural pattern in which only a single thiolato ligand is incorporated in the structure probably for steric reasons. It has a planar trapezoidal Cu4 core in which three Cu-Cu edges are bridged by the mesityl groups while the remaining Cu-Cu edge is thiolato ligand bridged. Dispersion connected DFT calculations show that 3 has the highest LD effect stabilization arising from the increased numbers of C-H···H-C interactions of the isopropyl ligand substituents.Peer reviewe

Hydrostannylation of Olefins by a Hydridostannylene Tungsten Complex

Hyväksytty takautuvasti osaksi ACS-OA-sopimusta (APC-tiimi 8. 12. 2022). Lisenssiä ei ollut vielä näkyvissä tallennushetkellä, tullee myöhemmin.Reaction of the aryltin(II) hydride {AriPr6Sn(mu- H)}2 (AriPr6 = -C6H3-2,6-(C6H2-2,4,6-iPr3)2) with two equivalents of the tungsten carbonyl THF complex, [W(CO)5(THF)], afforded the divalent tin hydride transition metal complex, W(CO)5{Sn(AriPr6)H}, (1). Complex 1 reacted rapidly with ethylene, or propylene under ambient conditions to yield the corresponding hydrostannylated organometallic species, W(CO)5{Sn(AriPr6)(Et)} (2), or W(CO)5{Sn(AriPr6)(nPr)} (3), via olefin insertion into the Sn-H bond. Treatment of 1 with the Lewis base dbu (dbu = 1,8-diazabicycloundec-7-ene) afforded the Lewis acid-base complex, W(CO)5{Sn(AriPr6)(dbu)H} (4), indicating that the Lewis acidity of the tin atom is preserved in 4. The complexes were characterized by X-ray crystallography, and by UV-visible, FT-IR, and multinuclear NMR spectroscopies. DFT calculations suggest hydrostannylation of ethylene with 1 proceeds via coordination of ethylene to the tin atom, then insertion into the Sn-H bond. Further computational study on the reactivity of 1 toward Ph3SiH indicated that the rate-determining step involves the metathesis reaction of a Sn-C/Si-H bond with a very high energy barrier of 71.3 kcal/mol. The calculated proton abstraction product of 1 with dbu, [W(CO)5{Sn(AriPr6)}]+[H-(dbu)]-, is 18.2 kcal/mol less stable than the observed coordination product 4.Peer reviewe

A pendant proton shuttle on [Fe4N(CO)12]- alters product selectivity in formate vs. H2 production via the hydride [H-Fe4N(CO)12].

Proton relays are known to increase reaction rates for H2 evolution and lower overpotentials in electrocatalytic reactions. In this report we describe two electrocatalysts, [Fe4N(CO)11(PPh3)]- (1-) which has no proton relay, and hydroxyl-containing [Fe4N(CO)11(Ph2P(CH2)2OH)]- (2-). Solid state structures indicate that these phosphine-substituted clusters are direct analogs of [Fe4N(CO)12]- where one CO ligand has been replaced by a phosphine. We show that the proton relay changes the selectivity of reactions: CO2 is reduced selectively to formate by 1- in the absence of a relay, and protons are reduced to H2 under a CO2 atmosphere by 2-. These results implicate a hydride intermediate in the mechanism of the reactions and demonstrate the importance of controlling proton delivery to control product selectivity. Thermochemical measurements performed using infrared spectroelectrochemistry provided pKa and hydricity values for [HFe4N(CO)11(PPh3)]-, which are 23.7, and 45.5 kcal mol-1, respectively. The pKa of the hydroxyl group in 2- was determined to fall between 29 and 41, and this suggests that the proximity of the proton relay to the active catalytic site plays a significant role in the product selectivity observed, since the acidity alone does not account for the observed results. More generally, this work emphasizes the importance of substrate delivery kinetics in determining the selectivity of CO2 reduction reactions that proceed through metal-hydride intermediates

Inhibition of Alkali Metal Reduction of 1-Adamantanol by London Dispersion Effects

A series of alkali metal 1-adamantoxide (OAd1) complexes of formula [M(OAd1)(HOAd1)2], where M=Li, Na or K, were synthesised by reduction of 1-adamantanol with excess of the alkali metal. The syntheses indicated that only one out of every three HOAd1 molecules was reduced. An X-ray diffraction study of the sodium derivative shows that the complex features two unreduced HOAd1 donors as well as the reduced alkoxide (OAd1), with the Ad1 fragments clustered together on the same side of the NaO3 plane, contrary to steric considerations. This is the first example of an alkali metal reduction of an alcohol that is inhibited from completion due to the formation of the [M(OAd1)(HOAd1)2] complexes, stabilized by London dispersion effects. NMR spectroscopic studies revealed similar structures for the lithium and potassium derivatives. Computational analyses indicate that decisive London dispersion effects in the molecular structure are a consequence of the many C−H⋅⋅⋅H−C interactions between the OAd1 groups.Peer reviewe

Miniaturization of Chemical Analysis Systems – A Look into Next Century's Technology or Just a Fashionable Craze?

Miniaturization of already existing techniques in on-line analytical chemistry is an alternative to compound-selective chemical sensors. Theory points in the direction of higher efficiency, faster analysis time, and lower reagent consumption. Micromachining, a well known photolithographic technique for structures in the micrometer range, is introduced and documented with structures as examples for flow injection analysis, electrophoresis, and a detector cell