In Vivo Probe of Lipid II‐Interacting Proteins

β‐Lactams represent one of the most important classes of antibiotics discovered to date. These agents block Lipid II processing and cell wall biosynthesis through inactivation of penicillin‐binding proteins (PBPs). PBPs enzymatically load cell wall building blocks from Lipid II carrier molecules onto the growing cell wall scaffold during growth and division. Lipid II, a bottleneck in cell wall biosynthesis, is the target of some of the most potent antibiotics in clinical use. Despite the immense therapeutic value of this biosynthetic pathway, the PBP–Lipid II association has not been established in live cells. To determine this key interaction, we designed an unnatural d ‐amino acid dipeptide that is metabolically incorporated into Lipid II molecules. By hijacking the peptidoglycan biosynthetic machinery, photoaffinity probes were installed in combination with click partners within Lipid II, thereby allowing, for the first time, demonstration of PBP interactions in vivo with Lipid II.     

Crystal Structure of an EMAP‐II‐Like Cytokine Released from a Human tRNA Synthetase

Aminoacyl‐tRNA synthetases catalyze the first step of protein synthesis by aminoacylation of tRNAs. Remarkably, biological fragments of two human enzymes – tyrosyl‐tRNA synthetase (TyrRS) and tryptophanyl‐tRNA synthetase – are active cytokines produced by proteolysis or alternative splicing. One is a C‐terminal fragment of TyrRS (C‐TyrRS) that has potent activity for chemotaxis of leukocytes and monocytes and for stimulating production of other cytokines. Significantly, the cytokine activity of C‐TyrRS is absent in the context of the full‐length native protein. Unknown is the mechanism by which domain‐release from the dimeric native protein activates the cytokine. Here, the crystal structure of C‐TyrRS is presented at 2.2 Å resolution. This structure is similar to that of endothelial monocyte‐activating protein II (EMAP‐II), with critical residues of a heptapeptide element important for chemotaxis activity exposed on the first strand of a β‐barrel of the monomeric unit. In contrast, the same residues of C‐TyrRS are buried in an operational model for native TyrRS. Importantly, C‐TyrRS is shown here to be monomeric when released from dimeric native TyrRS. Further analysis suggests that the critical residues are exposed when tRNA is bound. Thus, tRNA binding to native TyrRS may be an additional or alternative way to activate cytokine signaling.     

Heterometallic Fe2II–UV and Ni2II–UV Exchange‐Coupled Single‐Molecule Magnets: Effect of the 3 d Ion on the Magnetic Properties

Uranium‐based compounds have been put forward as ideal candidates for the design of single‐molecule magnets (SMMs) with improved properties, but to date, only two examples of exchange‐coupled 3d–5f SMM containing uranium have been reported and both are based on the Mn^II ion. Here we have synthesized the first examples of exchange‐coupled uranium SMMs based on Fe^II and Ni^II. The SMM behavior of these complexes containing a quasi linear {M?O?U?O?M} core arises from intramolecular Fe?U and Ni?U exchange interactions combined with the high Ising anisotropy of the uranyl(V) moiety. The measured values of the relaxation barrier (53.9±0.9 K in the UFe₂ complex and of 27.4±0.5 K in the UNi₂ complex) show clearly the dependency on the spin value of the transition metal, providing important new information for the future design of improved uranium‐based SMMs.     

Cobalt‐Catalyzed CH Arylations with Weakly‐Coordinating Amides and Tetrazoles: Expedient Route to Angiotensin‐II‐Receptor Blockers

Cobalt‐catalyzed C?H arylations enabled the synthesis of biaryl tetrazoles, which are key structural motifs in antihypertensive angiotensin‐II‐receptor blockers. Thus, weakly‐coordinating benzamides were employed for step‐economical C?H arylations with ample scope. Further, a low‐valent NHC complex enabled first cobalt‐catalyzed C?H functionalization by tetrazole assistance.     

Meta‐barium borate,II‐BaB2O4, at 163 and 293 K

The single‐crystal X‐ray diffraction structure analysis of an excellent non‐linear optical material, viz. II‐BaB₂O₄ or Ba₃(B₃O₆)₂, has been carried out at 163 and 293 K. The two sets of structural data are compared and indicate a significant shortening of the c axial length in the unit cell at 163 K, whereas the a and b axial lengths essentially do not change.     

Organic Spherical Nucleic Acids for the Transport of a NIR‐II‐Emitting Dye Across the Blood–Brain Barrier

DNA nanotechnology plays an increasingly important role in the biomedical field; however, its application in the design of organic nanomaterials is underexplored. Herein, we report the use of DNA nanotechnology to transport a NIR‐II‐emitting nanofluorophore across the blood–brain barrier (BBB), facilitating non‐invasive imaging of brain tumors. Specifically, the DNA block copolymer, PS‐b‐DNA, is synthesized through a solid‐phase click reaction. We demonstrate that its self‐assembled structure shows exceptional cluster effects, among which BBB‐crossing is the most notable. Therefore, PS‐b‐DNA is utilized as an amphiphilic matrix to fabricate a NIR‐II nanofluorephore, which is applied in in vivo bioimaging. Accordingly, the NIR‐II fluorescence signal of the DNA‐based nanofluorophore localized at a glioblastoma is 3.8‐fold higher than the NIR‐II fluorescence signal of the PEG‐based counterpart. The notably increased imaging resolution will significantly benefit the further diagnosis and therapy of brain tumors.     

Di‐ and tripeptide segments of zervamicin II‐2: Z‐Thr(OBn)‐Aib‐N(Me)Ph and Z‐Val‐Aib‐Hyp(OBn)‐OMe

The title compounds, O‐benzyl‐N‐(benzyl­oxy­carbonyl)­threonyl‐2,N‐dimethyl­alanin­anilide, C₃₀H₃₅N₃O₅, and methyl (4R)‐4‐benzyl­oxy‐N‐(benzyl­oxy­carbonyl)­valyl‐2‐(methyl­alanyl)prolinate, C₃₀H₃₉N₃O₇, were obtained from the `azirine coupling' of the corresponding protected amino acids with 2,2,N‐trimethyl‐2H‐azirin‐3‐amine and methyl (4R)‐4‐(benzyl­oxy)‐N‐(2,2‐dimethyl‐2H‐azirin‐2‐yl)prolinate, respectively. The Aib unit in each mol­ecule has the greatest turn‐ or helix‐inducing effect on the mol­ecular conformation. Inter­molecular N—H⋯O inter­actions link the mol­ecules of the tripeptide into sheets and those of the dipeptide into extended chains.     

Copolymerization of Ethylene with 1,9‐Decadiene: Part II—Prediction of Molecular Weight Distributions

In the present work, adaptive orthogonal collocation and a Monte Carlo method are used to compute the molecular weight distributions (MWD) of ethylene/1,9‐decadiene copolymers produced with a constrained geometry catalyst. Predictions from each model are compared to each other and to the experimental MWDs, allowing for the evaluation of relative strengths and weaknesses of each mathematical modeling method. Comparisons with experimental results indicate that the rate of macromonomer incorporation in the growing polymer chains decays with the macromonomer radius of gyration. In all cases, the proposed models are able to fit appropriately the available experimental MWDs.     

Novel calix[4]cryptands: “Mappemonde II” and “Mill II”

Two novel calix[4]cryptands were synthesized from 1,3‐alternate calix[4]bis‐azacrown. “Mappemonde II” consists of one 1,3‐calix[4]bis‐azacrown wrapped by a benzo‐crown ether loop. “Mill II” is composed of two 1,3‐calix[4]bis‐azacrowns linked by two benzo‐crown ether strands.     

Mixing Effects in Continuous Free‐Radical Solution Copolymerization Tank Reactors: II—Investigation of Micromixing Effects

The effect of micromixing on the dynamic behavior of continuous solution copolymerization tank reactors is evaluated both experimentally and theoretically. For this purpose, copolymerization reactions of styrene and divinylbenzene are carried out in a lab‐scale polymerization system, composed of two tank reactors in series, to provide experimental data of conversion and molar masses for analysis of micromixing effects. Besides, a detailed micromixing model, based on a dynamic population balance approach, is developed and solved with the method of characteristics, to investigate the micromixing effects on the dynamic behavior of conversion and molar masses in copolymerization reactions. Particularly, results show for the first time that micromixing effects can be important to explain the dynamic behavior of polymerization reactions performed in bulk, but are not sufficient to explain the whole set of available experimental data, which are much more sensitive to modification of residence time distributions and macromixing.     

Design,Synthesis, NMR‐Solution and X‐Ray Crystal Structure of N‐Acyl‐γ‐dipeptide Amides That Form a βII′‐Type Turn

Conformational analysis of γ‐amino acids with substituents in the 2‐position reveals that an N‐acyl‐γ‐dipeptide amide built of two enantiomeric residues of unlike configuration will form a 14‐membered H‐bonded ring, i.e., a γ‐peptidic turn (Figs. 1 – 3). The diastereoselective preparation of the required building blocks was achieved by alkylation of the doubly lithiated N‐Boc‐protected 4‐aminoalkanoates, which, in turn, are readily available from the corresponding (R)‐ or (S)‐α‐amino acids (Scheme 1). Coupling two such γ‐amino acid derivatives gave N‐acetyl and N‐[(tert‐butoxy)carbonyl] (Boc) dipeptide methyl amides ( 1 and 10 , resp.; Fig. 2, Scheme 2); both formed crystals suitable for X‐ray analysis, which confirmed the turn structures in the solid state (Fig. 4 and Table 4). NMR Analysis of the acetyl derivative 1 in CD₃OH, with full chemical‐shift and coupling assignments, and, including a 300‐ms ROESY measurement, revealed that the predicted turn structure is also present in solution (Fig. 5 and Tables 1 – 3). The results described here are yet another piece of evidence for the fact that more stable secondary structures are formed with a decreasing number of residues, and with increasing degree of predictability, as we go from α‐ to β‐ to γ‐peptides. Implications of the superimposable geometries of the actual turn segments (with amide bonds flanked by two quasi‐equatorial substituents) in α‐, β‐, and γ‐peptidic turns are discussed.     

Highly Sensitive Magnetic Effects Induced by Hydrogen‐Bonding Interactions in a High‐Spin Metallosupramolecular Fe4II [2×2] Grid‐Type Complex

A sensitive magnetic nanoprobe : Hydrogen‐bonding interactions are reflected with great sensitivity in the ¹H NMR spectra of a high‐spin multinuclear Fe₄^II [2×2] grid‐type complex (see scheme) and the measured shifts can be used to evaluate the hydrogen‐bond donating ability. The grid complex also represents a prototype of a very sensitive magnetic nanoreceptor for the detection of very small changes around a magnetic center.

     

Dry Sintering Meets Wet Silver‐Ion “Soldering”: Charge‐Transfer Plasmon Engineering of Solution‐Assembled Gold Nanodimers From Visible to Near‐Infrared I and II Regions

Achieving highly tunable and localized surface plasmon resonance up to near infrared (NIR) regions is a key target in nanoplasmonics. In particular, a self‐assembly process capable of producing highly uniform and solution‐processable nanomaterials with tailor‐made plasmonic properties is lacking. We herein address this problem through a conjunctive use of wet Ag⁺ soldering and dry thermal sintering to produce nanodimer‐derived structures with precisely engineered charge‐transfer plasmon (CTP). The sintered dimers are water soluble, featuring gradually shifted CTP spanning an 800 nm wavelength range (up to NIR II). Upon silica removal, the products are grafted by DNA to offer surface functionality. This process is also adaptable to DNA‐linked AuNP dimers toward plasmonic meta‐materials via DNA‐guided soldering and sintering.     

Study by ESI‐FTICRMS and ESI‐FTICRMSn of zinc and cadmium thiophenolate complexes used as precursors for the synthesis of II–VI nanosemiconductors

[M₄(SC₆H₅)₁₀][(CH₃)N]₂, [M₁₀L₄(SC₆H₅)₁₆][(CH₃)N]₄ and [Cd₁₇S₄(SC₆H₅)₂₈][(CH₃)N]₂(M = Cd or Zn, and L = S or Se) zinc and cadmium thiophenolates have been studied by electrospray ionization (ESI) Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (ESI‐FTICRMS) and tandem ESI‐FTICRMS (ESI‐FTICRMSⁿ). ESI‐FTICRMS demonstrated its ability to characterize and study such compounds, which may be used as precursors of II–VI nanomaterials. The obtained mass spectrum has been found to be highly relevant of the investigated thiophenolate and the fragmentation behavior of some of the detected ions is indicative of its stability. More specifically, it has been demonstrated that ESI in‐source activation or fragmentation experiments conducted in the Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS) cell induced the formation of a very stable entity, which corresponds to the general formula M₄L₄ (M = Zn or Cd and L = S or Se). The elimination of SC₆H₅^? and/or M(SC₆H₅)₂ moieties by various activation processes from the studied thiophenolates led systematically to this structure. Copyright © 2009 John Wiley & Sons, Ltd.