Theory-enforced Re-investigation of the Origin of the Large Metal–Carbon Bond Strength in PdCH2I+ and its reactions with unsaturated hydrocarbons

State-of-the-art ab initio studies demonstrate that the reaction Pd⁺ + CH₃I → PdCH₂I⁺ + H^. is endothermic by ca. 20 kcal/mol, which translates into a bond dissociation energy (BDE) of ca. 83 kcal/mol for the Pd⁺? CH₂I bond. This figure is in agreement with an experimental bracket of 68 kcal/mol < BDE(Pd⁺? CH₂I) < 92 kcal/mol. Based on these findings, the previously studied Pd⁺/CH₃I system was re-investigated, and double-resonance experiments demonstrate that the formation of PdCH₂I⁺ occurs stepwise via PdCH as a reactive intermediate. Further, ion/molecule reactions of PdCH₂I⁺ with unsaturated hydrocarbons are studied, which reveal the formation of carbon–carbon bonds in the gas phase.     

Development of a New Class of Inhibitors for the Malarial Aspartic Protease Plasmepsin II Based on a Central 7‐Azabicyclo[2.2.1]heptane Scaffold

Plasmepsin II (PMII), a malarial aspartic protease involved in the catabolism of hemoglobin in parasites of the genus Plasmodium, and renin, a human aspartic protease, share 35% sequence identity in their mature chains. Structures of 4‐arylpiperidine inhibitors complexed to human renin were reported by Roche recently. The major conformational changes, compared to a structure of renin, with a peptidomimetic inhibitor were identified and subsequently modeled in a structure of PMII (Fig. 1). This distorted structure of PMII served as active‐site model for a novel class of PMII inhibitors, according to a structure‐based de novo design approach (Fig. 2). These newly designed inhibitors feature a rigid 7‐azabicyclo[2.2.1]heptane scaffold, which, in its protonated form, is assumed to undergo ionic H‐bonding with the two catalytic Asp residues at the active site of PMII. Two substituents depart from the scaffold for occupancy of either the S1/S3 or S2′‐pocket and the hydrophobic flap pocket, newly created by the conformational changes in PMII. The inhibitors synthesized starting from N‐Boc‐protected 7‐azabicyclo[2.2.1]hept‐2‐ene ( 6 ; Schemes 1–5) displayed up to single‐digit micromolar activity (IC₅₀ values) toward PMII and good selectivity towards renin. The clear structure? activity relationship (SAR; Table) provides strong validation of the proposed conformational changes in PMII and the occupancy of the resulting hydrophobic flap pocket by our new inhibitors.     

Reaction properties of the trans-hyponitrite complex [Ru2(CO)4(mu-H)(mu-PBu(t)2)(mu-Ph2PCH2PPh2)(mu-eta2-ONNO)

The protonation of [Ru(2)(CO)(4)(mu-H)(mu-PBu(t)()(2))(mu-dppm)(mu-eta(2)-ONNO)] (1) with HBF(4) occurs at the oxygen of the noncoordinating side of the trans-hyponitrite ligand to give [Ru(2)(CO)(4)(mu-H)(mu-PBu(t)()(2))(mu-dppm)(mu-eta(2)-ONNOH)][BF(4)] (2) in good yield. The monoprotonated hyponitrite in 2 is deprotonated easily by strong bases to regenerate 1. Furthermore, 1 reacts with the methylating reagent [Me(3)O][BF(4)] to afford [Ru(2)(CO)(4)(mu-H)(mu-PBu(t)()(2))(mu-dppm)(mu-eta(2)-ONNOMe)][BF(4)] (3). The molecular structures of 2 and 3 have been determined crystallographically, and the structure of 2 is discussed with the results of the DFT/B3LYP calculations on the model complex [Ru(2)(CO)(4)(mu-H)(mu-PH(2))(mu-H(2)PCH(2)PH(2))(mu-eta(2)-ONNOH)](+) (2a). Moreover, the thermolysis of 2 in ethanol affords [Ru(2)(CO)(4)(mu-H)(mu-OH)(mu-PBu(t)()(2))(mu-dppm)][BF(4)] (4) in high yield, and the deprotonation of 4 by DBU in THF yields the novel complex [Ru(2)(CO)(4)(mu-OH)(mu-PBu(t)()(2))(mu-dppm)] (5).     

Recognition and catalysis in allylic alkylations

[structure: see text] A cavitand outfitted with a chelated palladium atom catalyzes allylic alkylation reactions. Molecular recognition by the cavitand distinguishes between closely related structures and results in subtle substrate specificities.     

Orthogonally Protected, Carboxy-Activated L-Homoisoserine, 2-Methyl-L-homoisoserine, and Homoisocysteine Derivatives. New Building Blocks for Peptide and Depsipeptide Modification

Starting from L-malic, L-citramalic, and rac. thiomalic acids routes to L-homoisoserine, 2-methyl-L-homoisoserine and rac. homoisocysteine have been developed. The new orthogonally protected and carboxy-activated building blocks are GABA as well as -hydroxy and -mercapto acid derivatives, suitable for the construction of peptide and depsipeptide surrogates.     

Thermodynamic equilibrium between locally excited and charge-transfer states through thermally activated charge transfer in 1-(pyren-2′-yl)-o-carborane

Reversible conversion between excited-states plays an important role in many photophysical phenomena. Using 1-(pyren-2′-yl)-o-carborane as a model, we studied the photoinduced reversible charge-transfer (CT) process and the thermodynamic equilibrium between the locally-excited (LE) state and CT state, by combining steady state, time-resolved, and temperature-dependent fluorescence spectroscopy, fs- and ns-transient absorption, and DFT and LR-TDDFT calculations. Our results show that the energy gaps and energy barriers between the LE, CT, and a non-emissive ‘mixed’ state of 1-(pyren-2′-yl)-o-carborane are very small, and all three excited states are accessible at room temperature. The internal-conversion and reverse internal-conversion between LE and CT states are significantly faster than the radiative decay, and the two states have the same lifetimes and are in thermodynamic equilibrium.

Reversible conversion between excited-states is key to many photophysical phenomena. We studied the equilibrium between LE and CT states by time-resolved and temperature-dependent fluorescence, fs- and ns-transient absorption, and LR-TDDFT calculations.     

Evolution of Artificial Arginine Analogues—Fluorescent Guanidiniocarbonyl-Indoles as Efficient Oxo-Anion Binders

In this article, we present fluorescent guanidiniocarbonyl-indoles as versatile oxo-anion binders. Herein, the guanidiniocarbonyl-indole (GCI) and methoxy-guanidiniocarbonyl-indole (MGCI) were investigated as ethylamides and compared with the well-known guanidiniocarbonyl-pyrrole (GCP) concerning their photophysical properties as well as their binding behavior towards oxo-anions. Hence, a variety of anionic species, such as carboxylates, phosphonates and sulfonates, have been studied regarding their binding properties with GCP, GCI and MGCI using UV-Vis titrations, in combination with the determination of the complex stoichiometry using the Job method. The emission properties were studied in relation to the pH value using fluorescence spectroscopy as well as the determination of the photoluminescence quantum yields (PLQY). Density functional theory (DFT) calculations were undertaken to obtain a better understanding of the ground-lying electronic properties of the investigated oxo-anion binders. Additionally, X-ray diffraction of GCP and GCI was conducted. We found that GCI and MGCI efficiently bind carboxylates, phosphonates and sulfonates in buffered aqueous solution and in a similar range as GCP (K_ass ≈ 1000–18,000 M⁻¹, in bis-tris buffer, pH = 6); thus, they could be regarded as promising emissive oxo-anion binders. They also exhibit a visible fluorescence with a sufficient PLQY. Additionally, the excitation and emission wavelength of MGCI was successfully shifted closer to the visible region of the electromagnetic spectrum by introducing a methoxy-group into the core structure, which makes them interesting for biological applications.     

Study of the properties of the SHG with diode lasers

An experimental study of the second-harmonic generation (SHG) properties with nondiffraction-limited radiation is presented. This includes the dependency of the normalized conversion efficiency on the crystal length, the beam quality, and the focusing conditions. A Gauss–Schell-model-based theory of SHG is applied, which gives an improved simulation of the experimental results in comparison to the standard Boyd–Kleinman theory for nondiffraction-limited beams.