A Predictive Model Towards Site‐Selective Metalations of Functionalized Heterocycles,Arenes, Olefins,and Alkanes using TMPZnCl⋅LiCl

The development of a predictive model towards site‐selective deprotometalation reactions using TMPZnCl?LiCl is reported (TMP=2,2,6,6‐tetramethylpiperidinyl). The pK_a values of functionalized N‐, S‐, and O‐heterocycles, arenes, alkenes, or alkanes were calculated and compared to the experimental deprotonation sites. Large overlap (>80 %) between the calculated and empirical deprotonation sites was observed, showing that thermodynamic factors strongly govern the metalation regioselectivity. In the case of olefins, calculated frozen state energies of the deprotonated substrates allowed a more accurate prediction. Additionally, various new N‐heterocycles were analyzed and the metalation regioselectivities rationalized using the predictive model.     

Vickers indentation hardness of Hg1−xCdxTe

The Vickers indentation hardness of Hg_1−xCd_xTe has been measured as a function of composition x using monocrystalline samples of Bridgman and THM crystals and polycrystalline starting material at room temperature. The microhardness varied between 220 MPa (x=0) and 440 MPa (x=1), showing a maximum of 850 MPa at x ∼ 0.75, and was different between monocrystalline and polycrystalline samples. The “hardening rate” dH/dx is strongly dependent on the composition range and is discussed in context with solid solution hardening due to elastic interactions of solute atoms with gliding dislocations and ordering effects.     

C=X π-Systeme

Im Rahmen des Graduiertenkollegs “Hochreaktive Mehrfachbindungssysteme” hatten G. Erker und J. Grobe vom 16. bis 18. November 1994 schon zum zweiten Mal nach Münster eingeladen. “Organic and Inorganic Chemistry of Reactive C=X π-Systems” waren diesmal das Thema.     

Deformation Induced Micro-Twins in CdTe?

Room- and high-temperature micro-indentation experiments have been performed to answer the question if, concerning a material with very low stacking-fault energy like CdTe, deformation induced twinning occurs in these substances during or shortly after growth. Micro-twins appear in consequence of room-temperature deformation only, whereas microindentation at 565°C does not produce any twins, but leads to widely expanded dislocation glide-figures, due to dislocation climbing and/or cross-gliding.     

Recognition hysteresis of the acetylcholine receptor of torpedo Californica

The nicotinic acetylcholine receptor (nAcChR) of the electric organ of Torpedo californica fish exhibits a pronounced hysteresis loop in the high affinity binding of the neurotransmitter acetylcholine (AcCh). When increasing amounts of AcCh are added (pulse mode) an extremely long-lived, metastable conformer distribution is obtained (lower hysteresis branch) between low affinity AcCh binding states (R_l) and high (R_h) and very high (R_vh) affinity states. Dialysis conditions always lead to the equilibrium binding curve (upper hysteresis branch; K̄_A = 5 × 10⁻⁹M, 4°C; one A bound to the R-monomer of M_r ≈ 290 000). Cyclic, pulse mode addition and dilution of AcCh results in scanning loops within the main hysteresis. The kinetic analysis of the changes in free and bound AcCh during the open-system conditions of dialysis, that releases the metastability, shows that the AcCh (A) binding proceeds along an induced-fit pathway according to A+R_h ⇋ AR_n ⇋ AR_vh. The rate constant of the step AR_h → AR_vh is k₂ = 6 × 10⁻³s⁻¹ and that of the reverse step is k₋₂ = 3 × 10⁻⁴s⁻¹. Direct binding of A to free R_vh can be excluded. Therefore, the state R_vh does not preexist, it is induced and only stable, as AR_vh, by bound AcCh. The metastability can be described in terms of long-lived AR_vh ·R₁ hybrid dimers. Physiologically, the metastable hybrid may be viewed as a saving device: the functionally important, channel-active R₁ conformer is, at low AcCh-concentrations [A] < 1μM, prevented to convert to the desensitized states R_h and AR_vh. Furtheron, AcCh enhances the phosphorylation of phosphatidyl inositol and the auto-phosphorylation of the receptor. If the AcCh binding hysteresis causes a phosphorylation hysteresis the desensitized nAcChR may serve as a memory molecule of the transsynaptic information signalling of the neurotransmission.     

Glenn Taylor: The horse who came to dinner: the first criminal case of food fraud

Analytical and Bioanalytical Chemistry -     

Dextramabs: A Novel Format of Antibody-Drug Conjugates Featuring a Multivalent Polysaccharide Scaffold

Antibody-drug conjugates (ADCs) are multicomponent biomolecules that have emerged as a powerful tool for targeted tumor therapy. Combining specific binding of an immunoglobulin with toxic properties of a payload, they however often suffer from poor hydrophilicity when loaded with a high amount of toxins. To address these issues simultaneously, we developed dextramabs, a novel class of hybrid antibody-drug conjugates. In these architectures, the therapeutic antibody trastuzumab is equipped with a multivalent dextran polysaccharide that enables efficient loading with a potent toxin in a controllable fashion. Our modular chemoenzymatic approach provides an access to synthetic dextramabs bearing monomethyl auristatin as releasable cytotoxic cargo. They possess high drug-to-antibody ratios, remarkable hydrophilicity, and high toxicity in vitro.