Ab initio path-integral molecular dynamics

A path-integral molecular dynamics technique for strongly interacting atoms using ab initio potentials derived from density functional theory is implemented. This allows the efficient inclusion of nuclear quantum dispersion in ab initio simulations at finite temperatures. We present an application to the quantum cluster H ₅ ⁺ .     

Selective Si--C bond cleavage as synthetic entry to a functionalized lithiosilane

Treatment of the phenyl-substituted silane 4 with lithium metal afforded the functionalized lithiosilane rac-2 by selective cleavage of one Si-C bond between silicon and a phenyl group. The resulting lithiosilane rac-2 crystallizes as the dimer (2.THF)2, which represents the first example of a dimeric organyl-substituted lithiosilane in the presence of THF.     

Isochorismate pyruvate lyase: a pericyclic reaction mechanism?

Isochorismate pyruvate lyase (IPL) catalyzes the cleavage of isochorismate to give salicylate and pyruvate, a key step in bacterial siderophore biosynthesis. We investigated the enzyme from Pseudomonas aeruginosa using isochorismate selectively deuterated at C2 as a substrate. Monitoring the reaction by 2H NMR spectroscopy revealed that the label is quantitatively transferred from C2 to C9, producing stoichiometric amounts of [3-2H]pyruvate as product. Moreover, the deuterium kinetic isotope effect of 2.34 +/- 0.08 on kcat indicates that C-H cleavage is significantly rate limiting. Consistent with these data, hybrid density functional theory (HDFT) calculations at the Becke3LYP/DZ+(2d,p) level of theory predict a concerted but highly asynchronous pericyclic transition structure, in which carbon-oxygen bond cleavage is more advanced than hydrogen atom transfer from C2 to C9; the calculated 2H isotope effect of 2.22 at C2 is in excellent accord with the experimental value. Together, these findings indicate that IPL should be added to the small set of proteins that are known to catalyze pericyclic reactions. They also raise the possibility that enzymes, such as chorismate pyruvate lyase, salicylate synthase, 4-amino-4-deoxychorismate lyase, and anthranilate synthase, which accelerate formally similar reaction steps, may also exploit pericyclic mechanisms.     

Simple spectrophotometric determination of Fe in oxalate and HCl soil extracts

We describe a spectrophotometric method to determine the sum of Fe(II) plus Fe(III) in HCl and oxalate extracts. The principle of the method is to reduce Fe(III) by ascorbate in near-neutral solution and to sequester the Fe(II) formed as a tri-ferrozine complex, which is then determined photometrically at 562 nm. Because the complex is stable, the reaction is irreversible and complete. Fe(III) in HCl solution reacted very rapidly, whereas oxalate decelerated the overall reaction so that pseudo first-order kinetics with respect to Fe(III) was detected. However, when extractions were conducted at the recommended soil:solution ratio, the absorption reached 98% of its final value within a few minutes. To test the method, four soils differing considerably in texture and carbonate, organic matter, and Fe(III)(hydr)oxide contents were extracted with oxalate in the dark for amorphous (Fe(o)), and with boiling oxalate for total Fe(III)(hydr)oxide (Fe(bo)). This newly developed spectrophotometric method showed excellent correspondence with the conventional atomic absorption spectroscopy (AAS) method. The method presented here can therefore be used as an alternative method to determine the Fe content of oxalate and hydrochloric acid extracts if AAS is not available. Oxalate extracts low in Fe content, which cannot be diluted, are easier to determine by the photometric method than by AAS.     

Intensification of Double Kinetic Resolution of Chiral Amines and Alcohols via Chemoselective Formation of a Carbonate–Enzyme Intermediate

Chiral amines and alcohols are synthons of numerous pharmaceutically-relevant compounds. The previously developed enzymatic kinetic resolution approaches utilize a chiral racemic molecule and achiral acyl donor (or acyl acceptor). Thus, only one enantiodivergent step of the catalytic cycle is engaged, which does not fully exploit the enzyme’s abilities. The first carbonate-mediated example of simultaneous double chemoselective kinetic resolution of chiral amines and alcohols is described. Herein, we established a biocatalytic approach towards four optically-pure compounds (>99% ee, Enantioselectivity: E > 200) via double enzymatic kinetic resolution, engaging chiral organic carbonates as acyl donors. High enantioselectivity was ensured by extraordinary chemoselectivity in lipase-catalyzed formation of unsymmetrical organic carbonates and engaged in a process applicable for the synthesis of enantiopure organic precursors of valuable compounds. This study focused not only on preparative synthesis, but additionally the catalytic mechanism was discussed and the clear impact of this rarely observed carbonate-derived acyl enzyme was shown. The presented protocol is characterized by atom efficiency, acyl donor sustainability, easy acyl group removal, mild reaction conditions, and biocatalyst recyclability, which significantly decreases the cost of the reported process.     

Influence of Aliphatic Chain Length on Structural,Thermal and Electrochemical Properties of n-alkylene Benzyl Alcohols: A Study of the Odd–Even Effect

The century-old, well-known odd–even effect phenomenon is still a very attractive and intriguing topic in supramolecular and nano-scale organic chemistry. As a part of our continuous efforts in the study of supramolecular chemistry, we have prepared three novel aromatic alcohols (1,2-bis[2-(hydroxymethyl)phenoxy]butylene (Do4OH), 1,2-bis[2-(hydroxymethyl)phenoxy]pentylene (Do5OH) and 1,2-bis[2-(hydroxymethyl)phenoxy]hexylene (Do6OH)) and determined their crystal and molecular structures by single-crystal X-ray diffraction. In all compounds, two benzyl alcohol groups are linked by an aliphatic chain of different lengths (CH₂)_n; n = 4, 5 and 6. The major differences in the molecular structures were found in the overall planarity of the molecules and the conformation of the aliphatic chain. Molecules with an even number of CH₂ groups tend to be planar with an all-trans conformation of the aliphatic chain, while the odd-numbered molecule is non-planar, with partial gauche conformation. A direct consequence of these structural differences is visible in the melting points—odd-numbered compounds of a particular series display systematically lower melting points. Crystal and molecular structures were additionally studied by the theoretical calculations and the melting points were correlated with packing density and the number of CH₂ groups. The results have shown that the generally accepted rule, higher density = higher stability = higher melting point, could not be applied to these compounds. It was found that the denser packaging causes an increase in the percentage of repulsive H‧‧‧H interactions, thereby reducing the stability of the crystal, and consequently, the melting points. Another interesting consequence of different molecular structures is their electrochemical and antioxidative properties—a non-planar structure displays the highest oxidation peak of hydroxyl groups and moderate antioxidant activity.     

Nanobodies: Chemical Functionalization Strategies and Intracellular Applications

Nanobodies can be seen as next‐generation tools for the recognition and modulation of antigens that are inaccessible to conventional antibodies. Due to their compact structure and high stability, nanobodies see frequent usage in basic research, and their chemical functionalization opens the way towards promising diagnostic and therapeutic applications. In this Review, central aspects of nanobody functionalization are presented, together with selected applications. While early conjugation strategies relied on the random modification of natural amino acids, more recent studies have focused on the site‐specific attachment of functional moieties. Such techniques include chemoenzymatic approaches, expressed protein ligation, and amber suppression in combination with bioorthogonal modification strategies. Recent applications range from sophisticated imaging and mass spectrometry to the delivery of nanobodies into living cells for the visualization and manipulation of intracellular antigens.     

Three Short Stories about Hexaarylbenzene–Porphyrin Scaffolds

A feasible two‐step synthesis and characterization of a full series of hexaarylbenzene (HAB) substituted porphyrins and tetrabenzoporphyrins is presented. Key steps represent the microwave‐assisted porphyrin condensation and the statistical Diels–Alder reaction to the desired HAB‐porphyrins. Regarding their applications, they proved to be easily accessible and effective high molecular mass calibrants for (MA)LDI mass spectrometry. The free‐base and zinc(II) porphyrin systems, as well as the respective tetrabenzoporphyrins, demonstrate in solid state experiments strong red‐ and near‐infrared‐light emission and are potentially interesting for the application in “truly organic” light‐emitting devices. Lastly, they represent facile precursors to large polycyclic aromatic hydrocarbon (PAH) substituted porphyrins. We prepared the first tetra‐hexa‐peri‐hexabenzocoronene substituted porphyrin, which represents the largest prepared PAH‐porphyrin conjugate to date.     

Inverse temperature transition of a biomimetic elastin model: reactive flux analysis of folding/unfolding and its coupling to solvent dielectric relaxation

The inverse temperature transition (ITT) of a biomimetic model for elastin, capped GVG(VPGVG) in liquid water, is investigated by a comprehensive classical molecular dynamics study. The temperature dependence of the solvation structure and dynamics of the octapeptide are compared using three common force fields, CHARMM, GROMOS, and OPLS. While these force fields differ in quantitative detail, they all predict this octapeptide to undergo a "folding transition" to closed conformations upon heating and a subsequent "unfolding transition" to open conformations at still higher temperatures, thus reproducing the ITT scenario. The peptide kinetics is analyzed within the reactive flux formalism applied to the largest-amplitude mode extracted from principal component analysis, and the solvent's dielectric fluctuations are obtained from the total water dipole autocorrelations. Most importantly, preliminary evidence for an intimate coupling of peptide folding/unfolding dynamics, and thus the ITT, and dielectric relaxation of bulk water is given, possibly being consistent with a "slave mode" picture.