Synthesis and Detection of BODIPY‐, Biotin‐, and 19F‐ Labeled Single‐Entity Dendritic Heparan Sulfate MimeticsSpijkers‐Shaw, Sam; Devlin, Rory; Shields, Nicholas J.; Feng, Xiang; Peck, Tessa; Lenihan‐Geels, Georgia; Davis, Connor; Young, Sarah L.; La Flamme, Anne C.; Zubkova, Olga V.
doi: 10.1002/anie.202316791pmid: 38308859
Heparin and heparan sulfate (HS) are naturally occurring mammalian glycosaminoglycans, and their synthetic and semi‐synthetic mimetics have attracted significant interest as potential therapeutics. However, understanding the mechanism of action by which HS, heparin, and HS mimetics have a biological effect is difficult due to their highly charged nature, broad protein interactomes, and variable structures. To address this, a library of novel single‐entity dendritic mimetics conjugated to BODIPY, Fluorine‐19 (19F), and biotin was synthesized for imaging and localization studies. The novel dendritic scaffold allowed for the conjugation of labeling moieties without reducing the number of sulfated capping groups, thereby better mimicking the multivalent nature of HS‐protein interactions. The 19F labeled mimetics were assessed in phantom studies and were detected at concentrations as low as 5 mM. Flow cytometric studies using a fluorescently labeled mimetic showed that the compound associated with immune cells from tumors more readily than splenic counterparts and was directed to endosomal‐lysosomal compartments within immune cells and cancer cells. Furthermore, the fluorescently labeled mimetic entered the central nervous system and was detectable in brain‐infiltrating immune cells 24 hours after treatment. Here, we report the enabling methodology for rapidly preparing various labeled HS mimetics and molecular probes with diverse potential therapeutic applications.
Cobalt‐Catalyzed Enantio‐ and Regioselective C(sp3)−H Alkenylation of ThioamidesStaronova, Lucia; Yamazaki, Ken; Xu, Xing; Shi, Heyao; Bickelhaupt, F. Matthias; Hamlin, Trevor A.; Dixon, Darren J.
doi: 10.1002/anie.202316021pmid: 38143241
An enantioselective cobalt‐catalyzed C(sp3)−H alkenylation of thioamides with but‐2‐ynoate ester coupling partners employing thioamide directing groups is presented. The method is operationally simple and requires only mild reaction conditions, while providing alkenylated products as single regioisomers in excellent yields (up to 85 %) and high enantiomeric excess [up to 91 : 9 enantiomeric ratio (er), or up to >99 : 1 er after a single recrystallization]. Diverse downstream derivatizations of the products are demonstrated, delivering a range of enantioenriched constructs. Extensive computational studies using density functional theory provide insight into the detailed reaction mechanism, origin of enantiocontrol, and the unusual regioselectivity of the alkenylation reaction.
Discovering Electrochemistry with an Electrochemistry‐Informed Neural Network (ECINN)Chen, Haotian; Yang, Minjun; Smetana, Bedřich; Novák, Vlastimil; Matějka, Vlastimil; Compton, Richard G.
doi: 10.1002/anie.202315937pmid: 38179808
Machine learning is increasingly integrated into chemistry research by guiding experimental procedures, correlating structure and function, interpreting large experimental datasets, to distill scientific insights that might be challenging with traditional methods. Such applications, however, largely focus on gaining insights via big data and/or big computation, while neglecting the valuable chemical prior knowledge dwelling in chemists’ minds. In this paper, we introduce an Electrochemistry‐Informed Neural Network (ECINN) by explicitly embedding electrochemistry priors including the Butler–Volmer (BV), Nernst and diffusion equations on the backbone of neural networks for multi‐task discovery of electrochemistry parameters. We applied the ECINN to voltammetry experiments of
Fe2+/Fe3+
${{\rm F}{{\rm e}}^{2+}/{\rm F}{{\rm e}}^{3+}}$
and
RuNH362+/RuNH363+
${{\rm R}{\rm u}{\left({\rm N}{{\rm H}}_{3}\right)}_{6}^{2+{\rm \ }}/{\rm R}{\rm u}{\left({\rm N}{{\rm H}}_{3}\right)}_{6}^{3+{\rm \ }}}$
redox couples to discover electrode kinetics and mass transport parameters. Notably, ECINN seamlessly integrated mass transport with BV to analyze the entire voltammogram to infer transfer coefficients directly, so offering a new approach to Tafel analysis by outdating various mass transport correction methods. In addition, ECINN can help discover the nature of electron transfer and is shown to refute incorrect physics if imposed. This work encourages chemists to embed their domain knowledge into machine learning models to start a new paradigm of chemistry‐informed machine learning for better accountability, interpretability, and generalization.
Dual‐Salt Electrolyte Additive Enables High Moisture Tolerance and Favorable Electric Double Layer for Lithium Metal BatteryWen, Zuxin; Fang, Wenqiang; Wang, Fenglin; Kang, Hong; Zhao, Shuoqing; Guo, Shaojun; Chen, Gen
doi: 10.1002/anie.202314876pmid: 38305641
The carbonate electrolyte chemistry is a primary determinant for the development of high‐voltage lithium metal batteries (LMBs). Unfortunately, their implementation is greatly plagued by sluggish electrode interfacial dynamics and insufficient electrolyte thermodynamic stability. Herein, lithium trifluoroacetate‐lithium nitrate (LiTFA−LiNO3) dual‐salt additive‐reinforced carbonate electrolyte (LTFAN) is proposed for stabilizing high‐voltage LMBs. We reveal that 1) the in situ generated inorganic‐rich electrode‐electrolyte interphase (EEI) enables rapid interfacial dynamics, 2) TFA− preferentially interacts with moisture over PF6− to strengthen the moisture tolerance of designed electrolyte, and 3) NO3− is found to be noticeably enriched at the cathode interface on charging, thus constructing Li+‐enriched, solvent‐coordinated, thermodynamically favorable electric double layer (EDL). The superior moisture tolerance of LTFAN and the thermodynamically stable EDL constructed at cathode interface play a decisive role in upgrading the compatibility of carbonate electrolyte with high‐voltage cathode. The LMBs with LTFAN realize 4.3 V‐NCM523/4.4 V‐NCM622 superior cycling reversibility and excellent rate capability, which is the leading level of documented records for carbonate electrode.
Nanoscale Visualization of Lithium Plating/Stripping Tuned by On‐site Formed Solid Electrolyte Interphase in All‐Solid‐State Lithium‐Metal BatteriesShen, Zhen‐Zhen; Zhang, Xu‐Sheng; Wan, Jing; Liu, Gui‐Xian; Tian, Jian‐Xin; Liu, Bing; Guo, Yu‐Guo; Wen, Rui
doi: 10.1002/anie.202316837pmid: 38315104
The interfacial processes, mainly the lithium (Li) plating/stripping and the evolution of the solid electrolyte interphase (SEI), are directly related to the performance of all‐solid‐state Li‐metal batteries (ASSLBs). However, the complex processes at solid‐solid interfaces are embedded under the solid‐state electrolyte, making it challenging to analyze the dynamic processes in real time. Here, using in situ electrochemical atomic force microscopy and optical microscopy, we directly visualized the Li plating/stripping/replating behavior, and measured the morphological and mechanical properties of the on‐site formed SEI at nanoscale. Li spheres plating/stripping/replating at the argyrodite solid electrolyte (Li6PS5Cl)/Li electrode interface is coupled with the formation/wrinkling/inflating of the SEI on its surface. Combined with in situ X‐ray photoelectron spectroscopy, details of the stepwise formation and physicochemical properties of SEI on the Li spheres are obtained. It is shown that higher operation rates can decrease the uniformity of the Li+‐conducting networks in the SEI and worsen Li plating/stripping reversibility. By regulating the applied current rates, uniform nucleation and reversible plating/stripping processes can be achieved, leading to the extension of the cycling life. The in situ analysis of the on‐site formed SEI at solid‐solid interfaces provides the correlation between the interfacial evolution and the electrochemical performance in ASSLBs.
Probing a Major DNA Weakness: Resolving the Groove and Sequence Selectivity of the Diimine Complex Λ‐[Ru(phen)2phi]2+Prieto Otoya, Tayler D.; McQuaid, Kane T.; Hennessy, Joseph; Menounou, Georgia; Gibney, Alex; Paterson, Neil G.; Cardin, David J.; Kellett, Andrew; Cardin, Christine J.
doi: 10.1002/anie.202318863pmid: 38271265
The grooves of DNA provide recognition sites for many nucleic acid binding proteins and anticancer drugs such as the covalently binding cisplatin. Here we report a crystal structure showing, for the first time, groove selectivity by an intercalating ruthenium complex. The complex Λ‐[Ru(phen)2phi]2+, where phi=9,10‐phenanthrenediimine, is bound to the DNA decamer duplex d(CCGGTACCGG)2. The structure shows that the metal complex is symmetrically bound in the major groove at the central TA/TA step, and asymmetrically bound in the minor groove at the adjacent GG/CC steps. A third type of binding links the strands, in which each terminal cytosine base stacks with one phen ligand. The overall binding stoichiometry is four Ru complexes per duplex. Complementary biophysical measurements confirm the binding preference for the Λ‐enantiomer and show a high affinity for TA/TA steps and, more generally, TA‐rich sequences. A striking enantiospecific elevation of melting temperatures is found for oligonucleotides which include the TATA box sequence.
Stabilization of Acenes: “Geländer”‐PentacenesLudwig, Philipp; Rominger, Frank; Freudenberg, Jan; Bunz, Uwe H. F.
doi: 10.1002/anie.202316902pmid: 38180106
We report soluble tetrakis‐biphenylyl substituted pentacenes comprised of sp2 carbons and synthesized from pentacene‐5,7,12,14‐tetraone. Intramolecular Yamamoto coupling of two tetrakis(chlorobiphenylyl)pentacenes yields helical, doubly wrapped pentacenes, in which the quaterphenylene units solubilize the pentacenes and shield their central anthracene units to an unprecedented degree. The criss‐cross‐bridged pentacenes resist (photo)oxidation, Diels–Alder reactions and are much less reactive than TIPS‐ethynylated pentacene. Extension of this concept might provide access to the larger acenes.