An Efficient Opal-Suppressor Tryptophanyl Pair Creates New Routes for Simultaneously Incorporating up to Three Distinct Noncanonical Amino Acids into Proteins in Mammalian Cells**

Site-specific incorporation of multiple distinct noncanonical amino acids (ncAAs) into proteins in mammalian cells is a promising technology, where each ncAA must be assigned to a different orthogonal aminoacyl-tRNA synthetase (aaRS)/tRNA pair that reads a distinct nonsense codon. Available pairs suppress TGA or TAA codons at a considerably lower efficiency than TAG, limiting the scope of this technology. Here we show that the E. coli tryptophanyl (EcTrp) pair is an excellent TGA-suppressor in mammalian cells, which can be combined with the three other established pairs to develop three new routes for dual-ncAA incorporation. Using these platforms, we site-specifically incorporated two different bioconjugation handles into an antibody with excellent efficiency, and subsequently labeled it with two distinct cytotoxic payloads. Additionally, we combined the EcTrp pair with other pairs to site-specifically incorporate three distinct ncAAs into a reporter protein in mammalian cells.     

Alkali Chloride Adducts of Acyclic Acylaluminum: Synthesis,Structure, and Reactivity Studies

Two acyclic acylaluminums and one cyclic acylaluminum dimer were synthesized by reaction of the recently reported Al-anion with acyl chloride. The reaction of the acylaluminums with TMSOTf and DMAP gave a ring-expanded iminium-substituted aluminate and a 2-C−H cleaved product. In the reaction of acylaluminums toward C=O and C=N bonds, acyclic acylaluminums reacted as an acyl nucleophile, while the cycilc dimer showed no reactivity. Amide-bond forming ligation using acyclic acylaluminums and hydroxylamines was further demonstrated. Throughout the study, acyclic acylaluminums exhibited higher reactivity than that of the cyclic dimer.     

Controlled Grafting Expansion Microscopy

Expansion microscopy (ExM) is a recently developed technique that allows for the resolution of structures below the diffraction limit by physically enlarging a hydrogel-embedded facsimile of the biological sample. The target structure is labeled and this label must be retained in a relative position true to the original, smaller state before expansion by linking it into the gel. However, gel formation and digestion lead to a significant loss in target-delivered label, resulting in weak signal. To overcome this problem, we have here developed an agent combining targeting, fluorescent labeling and gel linkage in a single small molecule. Similar approaches in the past have still suffered from significant loss of label. Here we show that this loss is due to insufficient surface grafting of fluorophores into the hydrogel and develop a solution by increasing the amount of target-bound monomers. Overall, we obtain a significant improvement in fluorescence signal retention and our new dye allows the resolution of nuclear pores as ring-like structures, similar to STED microscopy. We furthermore provide mechanistic insight into dye retention in ExM.     

Simultaneous Ring Contraction and Expansion Reaction: Electrosynthesis of Heterocycle-Fused Fulleroids and Photovoltaic Application

Simultaneous electrochemical ring contraction and expansion reactions remain unexplored to date. Herein, the reductive electrosynthesis of heterocycle-fused fulleroids from fullerotetrahydropyridazines and electrophiles in the presence of a trace amount of oxygen has been achieved with concurrent ring contraction and ring expansion. When trifluoroacetic acid and alkyl bromides are employed as electrophiles, heterocycle-fused fulleroids with a 1,1,2,6-configuration are regioselectively formed. In contrast, heterocycle-fused fulleroids with a 1,1,4,6-configuration are regioselectively produced as two separable stereoisomers if phthaloyl chloride is used as the electrophile. The reaction proceeds through multiple steps of electroreduction, heterocycle ring-opening, oxygen oxidation, heterocycle contraction, fullerene cage expansion, and nucleophilic addition. The structures of these fulleroids have been determined by spectroscopic data and single-crystal X-ray diffraction analyses. The observed high regioselectivities have been rationalized by theoretical calculations. Representative fulleroids have been applied in organic solar cells as the third component and exhibit good performance.     

Facile Synthesis of Nitrogen-Doped Nanographenes with Joined Nonhexagons via a Ring Expansion Strategy

Synthetic methodology is considered a holy grail in both organic chemistry and materials science. Over the past few decades, researchers have explored graphene-type molecules (or nanographenes) through classic Scholl oxidative cyclodehydrogenation. Despite the successes achieved with various nanographenes, the development of new methods to synthesize these highly desired molecules lags behind. Herein, we developed a facile and effective method to produce a series of nanographenes bearing nitrogen (N)-doped pentagon-heptagon pairs in acceptable yields. Modification of the heptagonal ring endowed the resultant nanographenes with tunable physicochemical properties; for instance, M9 exhibited both aggregation-caused quenching and aggregation-induced emission behavior. Most strikingly, novel nanographenes containing N-doped pentagon-octagon pairs were also obtained using the same synthetic strategy, demonstrating the superior versatility and efficiency of the proposed ring expansion method.     

Colossal Anisotropic Thermal Expansion through Coupling Spin Crossover and Rhombus Deformation in a Hexanuclear {FeIII4FeII2} Compound

Colossal and anisotropic thermal expansion is a key function for microscale or nanoscale actuators in material science. Herein, we present a hexanuclear compound of [(Tp*)Fe^III(CN)₃]₄[Fe^II(Ppmp)]₂⋅2 CH₃OH ( 1 , Tp*=hydrotris(3,5-dimethyl-pyrazol-1-yl)borate and Ppmp=2-[3-(2′-pyridyl)pyrazol-1-ylmethyl]pyridine), which has a rhombic core structure abbreviated as {Fe^III₂Fe^II₂}. Magnetic susceptibility measurements and single-crystal X-ray diffraction analyses revealed that 1 underwent thermally-induced spin transition with the thermal hysteresis. The Fe^II site in 1 behaved as a spin crossover (SCO) unit, and significant deformation of its octahedron was observed during the spin transition process. Moreover, the distortion of the Fe^II centers actuated anisotropic deformation of the rhombic {Fe^III₂Fe^II₂} core, which was spread over the whole crystal through the subsequent molecular rearrangements, leading to the colossal anisotropic thermal expansion. Our results provide a rational strategy for realizing the colossal anisotropic thermal expansion and shape memory effects by tuning the magnetic bistability.