Caterpillars with maximum degree 3 are antimagic

Let $G=(V,E)$ be a connected graph with $m$ edges. An antimagic labeling of $G$ is a one-to-one mapping from $E$ to $\{1,2,\dots ,m\}$ such that the vertex sum (i.e., sum of the labels assigned to edges incident to a vertex) for distinct vertices are different. A graph $G$ is called antimagic if $G$ has an antimagic labeling. It was conjectured by Hartsfield and Ringel that every tree other than $K_2$ is antimagic. The conjecture remains open though it was verified for trees with some constrains. Caterpillars are an important subclass of trees. This paper shows caterpillars with maximum degree 3 are antimagic, which gives an affirmative answer to an open problem of Lozano et al. (2019).     

An Unusual Conversion of 2‐(Alkynonyl)Alkynylbenzenes to Isocoumarins by a Retro‐Favorskii‐like Degradation

We report the discovery of an anomalous reaction of 2‐(alkynonyl)alkynylbenzenes under Ag^I catalysis for the selective formation of isocoumarins. This reaction is previously undocumented for 2‐(alkynonyl)alkynylbenzenes in terms of the reaction mechanism and the product formed. Water (H₂O¹⁸) labeling studies suggested a possible mechanistic pathway in which the initial formation of a pyrylium ion is followed by hydrative dealkynylation, that is, water incorporation and alkyne expulsion, similar to a retro‐Favorskii reaction.     

Modifying LnHPDO3A Chelates for Improved T1 and CEST MRI Applications

The new ligand HPDO3MA [(R,R,R,R)-10-(2-hydroxypropyl)-α,α′,α′′-trimethyl-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid] was designed to combine and optimize the chemical properties of the macrocyclic ligands HPDO3A and DOTMA. The presence of the methyl groups on the acetic pendant arms of HPDO3A is expected to rigidify the structure of the ligand and favor an increase of the kinetic inertness of the Ln complexes. ¹H NMR spectra of Eu(HPDO3MA) displayed the presence of two pairs of diastereoisomers: SAP (square antiprismatic) and TSAP (twisted square antiprismatic) isomers (56 and 44 %, respectively). In addition, ¹H and ¹⁷O relaxometric NMR studies of Gd(HPDO3MA) showed approximately a 10 % increase in relaxivity and a faster water exchange rate with respect to Gd(HPDO3A). Moreover, a detailed chemical exchange saturation transfer (CEST) characterization of Yb(HPDO3MA) displayed a sensitivity about two times larger than that of Yb(HPDO3A) both in phantom and in cell labeling experiments. Finally, the kinetic inertness of Yb(HPDO3MA) was measured to be twice as high as that of Yb(HPDO3A), with a dissociation half-life at physiological pH of about 2500 years.     

Bio‐orthogonal AIE Dots Based on Polyyne‐Bridged Red‐emissive AIEgen for Tumor Metabolic Labeling and Targeted Imaging

In this work, we aim to develop cancer cell‐targeting AIE dots based on a polyyne‐bridged red‐emissive AIEgen, 2TPE‐4E, through the combination of metabolic engineering and bio‐orthogonal reactions. Azide groups on a tumor were efficiently produced by intravenous injection of Ac4ManNAz and glycol‐metabolic engineering. These bio‐orthogonal azide groups could facilitate the specific targeting of DBCO‐AIE dots to the tumor cells undergoing metal‐free click reaction in vivo. The efficiency of this targeting strategy could be further improved with the development of new bio‐orthogonal chemical groups with higher reactivity and a large amount of AIEgens could be delivered to the tumor for diagnosis.     

Structural Manipulation of Ruthenium(II) Polypyridine Nitrone Complexes to Generate Phosphorogenic Bioorthogonal Reagents for Selective Cellular Labeling

We report a new class of ruthenium(II) polypyridine complexes functionalized with a nitrone group as phosphorogenic bioorthogonal probes. These complexes were very weakly emissive owing to rapid C=N isomerization of the nitrone moiety, but exhibited significant emission enhancement upon strain‐promoted alkyne–nitrone cycloaddition (SPANC) reaction with bicyclo[6.1.0]nonyne (BCN)‐modified substrates. The modification of nitrone with a dicationic ruthenium(II) polypyridine unit at the α‐C‐position and a phenyl ring at the N‐position led to remarkably accelerated reaction kinetics, which are substantially greater (up to ≈278 fold) than those of other acyclic nitrone–BCN systems. Interestingly, the complexes achieved specific cell membrane/cytosol staining upon specific labeling of an exogenous substrate, BCN‐modified decane (BCN‐C10), in live cells. Importantly, the in situ generation of the more lipophilic isoxazoline adduct in the cytoplasm resulted in increased cytotoxicity, highlighting a novel approach to apply the SPANC labeling technique in drug activation.     

The production of enantiomerically pure 1-phenylethanol by enzymatic kinetic resolution method using response surface methodology

As the enantiomers of 1-phenylethanol are valuable intermediates in several industries, the lipase catalyzed kinetic resolution of (R,S) -1-phenylethanol is a relevant research topic. In this study, the goal was to determine the optimum reaction parameters to produce enantiomerically pure 1-phenylethanol by lipase (Novozyme 435) catalyzed kinetic resolution using response surface methodology (RSM). Reactions were performed with 40–400 mM (R,S)-1-phenylethanol, 120–1200 mM vinyl acetate and 2–22 mg/mL biocatalyst concentrations (BC _L ), at 20–60 °C and with a stirring rate of 50–400 rpm for 5–120 min. The samples were analyzed using high performance liquid chromatography (HPLC) with a Chiralcel OB column. Optimum reaction parameters to reach 100% enantiomeric excess for the substrate ( ee _s ) were determined as follows: substrate concentration (C _s ): 240 mM, BC _L : 11 mg/mL, at 42 °C with a reaction time of 75 min. Model validation was performed using these conditions and ee _s was calculated as 100%, which indicates the predicted model was efficient and accurate. When compared to the literature, it was observed that the reaction time decreased significantly. This is an important result considering the industrial scale perspective.     

Magnetic Micromotors for Multiple Motile Sperm Cells Capture,Transport, and Enzymatic Release

An integrated system combining a magnetically-driven micromotor and a synthetized protein-based hyaluronic acid (HA) microflake is presented for the in situ selection and transport of multiple motile sperm cells (ca. 50). The system appeals for targeted sperm delivery in the reproductive system to assist fertilization or to deliver drugs. The binding mechanism between the HA microflake and sperm relies on the interactions between HA and the corresponding sperm HA receptors. Once sperm are captured within the HA microflake, the assembly is trapped and transported by a magnetically-driven helical microcarrier. The trapping of the sperm-microflake occurs by a local vortex induced by the microcarrier during rotation-translation under a rotating magnetic field. After transport, the microflake is enzymatically hydrolyzed by local proteases, allowing sperm to escape and finally reach the target location. This cargo-delivery system represents a new concept to transport not only multiple motile sperm but also other actively moving biological cargoes.     

Aromatic 19F–13C TROSY—[19F, 13C]-Pyrimidine Labeling for NMR Spectroscopy of RNA

We present the access to [5-¹⁹F, 5-¹³C]-uridine and -cytidine phosphoramidites for the production of site-specifically modified RNAs up to 65 nucleotides (nts). The amidites were used to introduce [5-¹⁹F, 5-¹³C]-pyrimidine labels into five RNAs—the 30 nt human immunodeficiency virus trans activation response (HIV TAR) 2 RNA, the 61 nt human hepatitis B virus ϵ (hHBV ϵ) RNA, the 49 nt SAM VI riboswitch aptamer domain from B. angulatum, the 29 nt apical stem loop of the pre-microRNA (miRNA) 21 and the 59 nt full length pre-miRNA 21. The main stimulus to introduce the aromatic ¹⁹F–¹³C-spin topology into RNA comes from a work of Boeszoermenyi et al., in which the dipole-dipole interaction and the chemical shift anisotropy relaxation mechanisms cancel each other leading to advantageous TROSY properties shown for aromatic protein sidechains. This aromatic ¹³C–¹⁹F labeling scheme is now transferred to RNA. We provide a protocol for the resonance assignment by solid phase synthesis based on diluted [5-¹⁹F, 5-¹³C]/[5-¹⁹F] pyrimidine labeling. For the 61 nt hHBV ϵ we find a beneficial ¹⁹F–¹³C TROSY enhancement, which should be even more pronounced in larger RNAs and will facilitate the NMR studies of larger RNAs. The [¹⁹F, ¹³C]-labeling of the SAM VI aptamer domain and the pre-miRNA 21 further opens the possibility to use the biorthogonal stable isotope reporter nuclei in in vivo NMR to observe ligand binding and microRNA processing in a biological relevant setting.     

Enhanced Sensitivity to Local Dynamics in Peptides by Use of Temperature-Jump IR Spectroscopy and Isotope Labeling

Site-specific isotopic labeling of molecules is a widely used approach in IR spectroscopy to resolve local contributions to vibrational modes. The induced frequency shift of the corresponding IR band depends on the substituted masses, as well as on hydrogen bonding and vibrational coupling. The impact of these different factors was analyzed with a designed three-stranded β-sheet peptide and by use of selected ¹³C isotope substitutions at multiple positions in the peptide backbone. Single-strand labels give rise to isotopically shifted bands at different frequencies, depending on the specific sites; this demonstrates sensitivity to the local environment. Cross-strand double- and triple-labeled peptides exhibited two resolved bands that could be uniquely assigned to specific residues, the equilibrium IR spectra of which indicated only weak local-mode coupling. Temperature-jump IR laser spectroscopy was applied to monitor structural dynamics and revealed an impressive enhancement of the isotope sensitivity to both local positions and coupling between them, relative to that of equilibrium FTIR spectroscopy. Site-specific relaxation rates were altered upon the introduction of additional cross-strand isotopes. Likewise, the rates for the global β-sheet dynamics were affected in a manner dependent on the distinct relaxation behavior of the labeled oscillator. This study reveals that isotope labels provide not only local structural probes, but rather sense the dynamic complexity of the molecular environment.