Transition Metal Templates Research Articles

Immunomodulatory microneedle patch for enhanced Ferroptosis and immunogenic cell death in postoperative tumor therapy

Microneedle technologies have emerged as a promising transdermal drug delivery platform for postoperative tumor therapy. Despite their potential, enhancing intracellular drug delivery to tumor cells and boosting the therapeutic efficiency of microneedles pose significant challenges. Herein, we develop a nanomedicine-loaded microneedle to enhance the induction of ferroptosis and immunogenic cell death for postoperative tumor therapy. This advancement is achieved by pre-formulating small molecule drugs with transition metal and protein templates into nanomedicine. Upon insertion into the tumors, the microneedle rapidly dissolves, facilitating the release and subsequent cellular uptake of the nanomedicine by tumor cells. Notably, the nanomedicine can release Mn ions and ferroptosis-inducer sulfasalazine (SAS) under acidic conditions. Furthermore, the released Mn ions can produce reactive oxygen species, which decrease the levels of glutathione (GSH) and glutathione peroxidase 4 (GPX4) with increased lipid peroxidation and enhanced induction of ferroptosis. Besides, the treatment stimulates immunogenic cell death through the cell surface exposure of calreticulin (CRT) and release of high-mobility group box 1 (HMGB1), which further stimulates dendric cell maturation, T cell infiltration, and macrophage polarization towards the M1 phenotype. Consequently, this strategy significantly inhibits postoperative tumor regrowth and extends overall survival. Our study indicates the potential of the combination of nanomedicine and microneedle to improve postoperative therapeutic efficiency.

Small Ring Molecules Comprising 3-6 Boron Atoms: An Account on Synthesis, Structure, and Orbital Engineering.

ConspectusUnlike carbon, boron does not usually form ring compounds due to its electron-deficiency-driven affinity toward polyhedral geometries. The polyhedral boranes having closo-, nido-, arachno-, or hypho-shapes can be structurally and electronically correlated using various electron counting rules developed by Wade, Mingos, and one of us. However, in the last few decades, boron chemistry progressed significantly toward ring systems. In this regard, three of our research groups have made significant contributions to the development of boron ring molecules through different synthetic approaches. While the Ghosh group generally starts from transition metal (TM) stabilized boron species, the Himmel group typically starts from electron-deficient TM-free boron ring compounds. On the other hand, the Jemmis group studies boron rings and their analogous structures computationally and develops electron counting rules to describe them. Over the past few years, through different synthetic approaches, several boron ring molecules have been prepared by our research groups and others. Recently, the Ghosh group has reported the synthesis of an almost planar B6-ring that is stabilized by a TM template. Similarly, the B3-, B4-, and B5-rings have also been stabilized in the coordination spheres of early and late TMs. The recent work of Himmel has uncovered some remarkable diversity in the structures and bonding of B3 and B4 rings, along with their redox reactions. The well-known hydrocarbon analogues of these borane rings, i.e., two-dimensional aromatic compounds [C3H3]+, [C5H5]-, [C6H6], etc., are governed by Hückel's (4n + 2) π-electron rule. However, planar or nearly planar borane rings are not seriously thought of as achievable targets. One of the reasons for this is the influence of the Rudolph diagram in the thought process of chemists that the nido- and arachno-structures generated from closo-polyhedral boranes must also be three-dimensional (3D) fragments. However, this is not the only possibility. Flat arachno- and nido-boranes reminiscent of their organic counterparts follow from an equivalent of the Rudolph diagram. Therefore, this Account is very much necessary for the boron community, in particular, to design and synthesize 3-6 membered boron rings or beyond. This Account aims to highlight significant ongoing experimental and theoretical results in this area from our groups, in addition to relevant works from other groups wherever appropriate. This will also bring into focus various ways in which the flat Bn-systems can be stabilized, such as the utilization of TM or main group caps, utilization of various Lewis bases, edge-condensation of small rings, control over the electron count, and orbital engineering.

The sharp structural switch of covalent cages mediated by subtle variation of directing groups

It is considered a more formidable task to precisely control the self-assembled products containing purely covalent components, due to a lack of intrinsic templates such as transition metals to suppress entropy loss during self-assembly. Here, we attempt to tackle this challenge by using directing groups. That is, the self-assembly products of condensing a 1:2 mixture of a tetraformyl and a biamine can be precisely controlled by slightly changing the substituent groups in the aldehyde precursor. This is because different directing groups provide hydrogen bonds with different modes to the adjacent imine units, so that the building blocks are endowed with totally different conformations. Each conformation favors the formation of a specific product that is thus produced selectively, including chiral and achiral cages. These results of using a specific directing group to favor a target product pave the way for accomplishing atom economy in synthesizing purely covalent molecules without relying on toxic transition metal templates.

Helicity-modulated remote C-H functionalization.

Remote C-H functionalization is highly important for the conversion and utilization of arenes, but the conventional routes are comprehensively developed with the assistance of transition metal catalysts or templates. We report a facile metal/template-free electrochemical strategy for remote C-H functionalization in a helical system, where aromatic or aliphatic hydrogen act as a directing group to promote the alkoxylation at the opposite site of the helical skeleton by generating a unique helical "back-biting" environment. Such helicity-modulated C-H functionalization is prevalent for carbo[n]helicenes (n=6 to 9, primitive or substituted) and hetero[6]helicenes and also occurs when the aryl hydrogen on the first position is replaced by a methyl group or a phenyl group. Thus, the relatively inert helicene skeleton can be precisely furnished with a rich array of alkoxy pendants with tunable functional moieties. Notably, the selective decoration of a methoxy group on N-methylated aza[6]helicene close or distant to the nitrogen atom leads to distinct luminescence variation upon changing the solvents.

A Brief History of Photoactive Interlocked Systems Assembled by Transition Metal Template Synthesis

More than three decades of research efforts have yielded powerful methodologies based on transition metal template-directed syntheses for the assembly of a huge number of interlocked systems, molecular knots, machines and synthesizers. Such template techniques have been applied in the preparation of mechanically linked electron donor–acceptor artificial photosynthetic models. Consequently, synthetic challenging photoactive rotaxanes and catenanes have been reported, in which the chromophores are not covalently linked but are still associated with undergoing sequential energy (EnT) and electron transfer (ET) processes upon photoexcitation. Many interlocked photosynthetic models produce highly energetic, but still long-living charge separated states (CSS). The present work describes in a historical perspective some key advances in the field of photoactive interlocked systems assembled by transition metal template techniques, which illustrate the usefulness of rotaxanes and catenanes as molecular scaffolds to organize electron donor–acceptor groups. The effects of molecular dynamics, molecular topology, as well as the role of the transition metal ion used as template species, on the thermodynamic and kinetic parameters of the photoinduced energy and electron transfer processes in the interlocked systems are also discussed.

Fabrication and characterization of few-layer graphene

Few-layer graphene were produced on transition-metal templates by using super-short-pulse laser produced plasma deposition techniques. Transparent few-layer graphene with the average thickness less than 8 nm, width up to 350 nm, and length more than 3 μm were successfully obtained. An unusual edge reconstruction was observed: a double layer folded back on itself, representing four layers. Wrinkles were found within the few-layer graphene, which is likely due to the presence of nanoparticles underneath the few-layer graphene causing distortion. This method of growing few-layer graphene can provide valuable information for understanding the growth mechanism of graphene, which may facilitate its controllable synthesis and applications.

Synthesis and Characterization of the First 1‐D Borate Templated by Transition Metal Complex

AbstractA novel decaborate compound, [Ag(py)2]2[B10O14(OH)4] (py = pyridine) (1), has been hydrothermally synthesized and structurally characterized by single crystal X‐ray diffraction, FTIR, elemental analysis, and thermogravimetric analysis. The compound crystallizes in the monoclinic system, space group P21/c (No. 14), a = 15.7115(7), b = 13.1477(6), c = 16.9463(8) Å, β = 105.2690(2)°, V = 3377.0(3) Å3, and Z = 4. The structure of the compound consists of infinite unusual wave‐like borate chains constructed from large [B10O14(OH)4]2− groups. It represents the first example of a one‐dimensional borate templated by a transition metal complex. Adjacent borate chains are further linked together by extensive hydrogen bonds to form a 3D supramolecular network with regular cyclic‐ and ellipse‐like channels, in which the transition metal templates [Ag(py)2]+ reside.

Coordination Chemistry of Ene‐1,1‐diamines and a Prototype “Carbodicarbene”

Carbophilic Lewis acids can polarize a coordinated π-bond by a slippage mechanism. A series of stable ylid- or enolate gold complexes of ene-1,1-diamines not only emulate this property, but also reveal the exceptional donor capacity of such electron-rich olefin ligands. Moreover, the first metal complex of a tetraaminoallene is reported, which features a prototype “carbodicarbene” ligand bound to a transition-metal template.

Epitaxial graphene on ruthenium

Graphene has been used to explore the fascinating electronic properties of ideal two-dimensional carbon, and shows great promise for quantum device architectures. The primary method for isolating graphene, micromechanical cleavage of graphite, is difficult to scale up for applications. Epitaxial growth is an attractive alternative, but achieving large graphene domains with uniform thickness remains a challenge, and substrate bonding may strongly affect the electronic properties of epitaxial graphene layers. Here, we show that epitaxy on Ru(0001) produces arrays of macroscopic single-crystalline graphene domains in a controlled, layer-by-layer fashion. Whereas the first graphene layer indeed interacts strongly with the metal substrate, the second layer is almost completely detached, shows weak electronic coupling to the metal, and hence retains the inherent electronic structure of graphene. Our findings demonstrate a route towards rational graphene synthesis on transition-metal templates for applications in electronics, sensing or catalysis.

3+2] Cycloaddition of Trimethylenemethane and Its Synthetic Equivalents

AbstractFor Abstract see ChemInform Abstract in Full Text.

A [2]Catenane Containing 1,1′‐Binaphthyl Units and 1,10‐Phenanthroline Fragments: Synthesis and Intermolecular Energy Transfer Processes

AbstractA chiral copper(I)‐complexed [2]catenane consisting of two interlocking 38‐membered rings, each ring incorporating a 2,9‐diphenyl‐1,10‐phenanthroline (dpp) and an (S)‐1,1′‐binaphthyl group, has been prepared by means of a transition metal template strategy. Demetalation afforded the corresponding free chiral [2]catenane. The coordination polyhedron of the Cu(dpp)2 core in this chiral copper(I)‐complexed [2]catenane reflects the distortion of the chiral 1,1′‐binaphthyl units, as evidenced by the circular dichroism (CD) measurements. Emission measurements demonstrated that in the two‐chromophore compounds (S)‐6 and (S,S)‐9, efficient energy transfer between the 1,1′‐binaphthyl component and the dpp unit takes place in solution at room temperature. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Reversible Carbon−Carbon Double Bond Cleavage of a Ketene Ligand at a Single Iridium(I) Center: A Theoretical Study

Modeling the chemistry of ketene complex {κ2-(t-Bu)2PCH2P(t-Bu)2}IrCl[η2-(C,C)-Ph2CCO] (1), DFT studies have been carried out for (κ2-H2PCH2PH2)IrCl[η2-(C,C)-H2CCO] (A), for cation (κ2-H2PCH2PH2)Ir[η2-(C,C)-CH2CO]+ (B), for its carbene carbonyl isomer (κ2-H2PCH2PH2)Ir(CH2)(CO)+ (C), and for their interconversion by intramolecular CC double bond cleavage/formation. A qualitative MO analysis from extended Hückel calculations shows the CC cleavage and formation to be symmetry allowed at a d8-ML2 late transition metal template. For the two iridium model complexes B and C the process is calculated by DFT to be reversible, with activation barriers of 17.3 kcal mol-1 toward the more stable carbonyl carbene system and 25.1 kcal mol-1 for the reverse reaction, respectively. This is in line with experimental observations for 1, which generates {κ2-(t-Bu)2PCH2P(t-Bu)2}Ir(CPh2)(CO)+ (3) upon chloride abstraction and regenerates 1 after the addition of chloride. QM/MM calculations of the ONIOM type have been employed for the real systems 1 and 3, to take into account and to evaluate the role of steric effects and to allow a validation of theoretical results by comparing computed and X-ray-determined structures. Contrasting the iridium case, the analogous rhodium ketene complex (κ2-H2PCH2PH2)Rh[η2-(C,C)-CH2CO]+ (G) is computed to be favored by 8.0 kcal mol-1 compared to its carbene carbonyl isomer (κ2-H2PCH2PH2)Rh(CH2)(CO)+ (H), with a barrier of 22.9 kcal mol-1 for the endothermic CC cleavage step. Conceivable dynamic processes were treated theoretically for the temperature dependence of NMR line shapes of carbene complex {κ2-(t-Bu)2PCH2P(t-Bu)2}Ir(CPh2)(CO)+ (3). A comparison with the experimental data suggests a plausible pathway for the observed exchange of the two P centers.

Double-level "orthogonal" dynamic combinatorial libraries on transition metal template.

Dynamic combinatorial libraries are mixtures of compounds that exist in a dynamic equilibrium and can be driven to compositional self adaptation via selective binding of a specific assembly of certain components to a molecular target. We present here an extension of this initial concept to dynamic libraries that consists of two levels, the first formed by the coordination of terpyridine-based ligands to the transition metal template, and the second, by the imine formation with the aldehyde substituents on the terpyridine moieties. Dialdehyde 7 has been synthesized, converted into a variety of ligands, oxime ethers L(11)-L(33) and acyl hydrazones L(44)-L(77), and subsequently into corresponding cobalt complexes. A typical complex, Co(L(22))(2)(2+) is shown to engage in rapid exchange with a competing ligand L(11) and with another complex, Co(L(22))(2)(2+) in 30% acetonitrile/water at pH 7.0 and 25 degrees C. The exchange in the corresponding Co(III) complexes is shown to be much slower. Imine exchange in the acyl hydrazone complexes (L(44)-L(77)) is strongly controlled by pH and temperature. The two types of exchange, ligand and imine, can thus be used as independent equilibrium processes controlled by different types of external intervention, i.e., via oxidation/reduction of the metal template and/or change in the pH/temperature of the medium. The resulting double-level dynamic libraries are therefore named orthogonal, in similarity with the orthogonal protecting groups in organic synthesis. Sample libraries of this type have been synthesized and showed the complete expected set of components in electrospray ionization MS.

Cycloisomerization of Alkynols at Transition Metal Templates

The metal-assisted cycloisomerization of ω-alkynols to oxacycloalkylidene complexes is reviewed. A variety of low-valent coordinatively unsaturated transition metal templates from group 6 to 10 mediate the cyclization of ω-butynols, -pentynols, and -hexynols to give the corresponding oxacycloalkylidene complexes. In some cases kinetic hydroxyalkylvinylidene complex intermediates can be isolated and characterized.

Transition-metal template synthesis of a rotaxane incorporating two different coordinating units in its thread

A [2]rotaxane consisting of a molecular string threaded into a coordinating ring by means of the template effect of copper (I) has been synthesized. The acyclic fragment incorporates two different chelating sites (bidentate and terdentate ligands) whereas the macrocycle bears a bidentate chelate. Two bulky groups have been covalently attached at the ends of the thread.

Assembling Organic Receptors around Transition Metal Templates: Functionalized Catechols and Dioxomolybdenum(VI) for the Recognition of Dicarboxylic Acids

The synthesis of two receptors for dicarboxylic acids [12](2)(-) and [13](2)(-), based on the self arrangement of two functionalized catechols 1 and 2 around a cis-[MoO(2)](2)(+) core, is described. Among the three pairs of enantiomers which may be produced during the complexation of two unsymmetrical catecholates around one molybdenum(VI) ion, only one is observed for each catechol derivative 1 or 2. Depending on the base used during the complexation of catechols to the molybdenum atom, the dianionic receptors obtained display different solubility properties. These molybdenum-based receptors are chromogenic and, in methylene chloride, the affinities of the assembled receptors for dicarboxylic acids ranging from C(4) to C(8) have been assessed by UV-visible titrations after determining the stoichiometry of the complex formation using Job's method. While receptor [12](2)(-) displays selectivity for C(4) and C(5) acids, the more flexible receptor [13](2)(-) exhibits selectivity for C(7) and C(8). The binding mode of the diacids to the molybdenum receptor has been determined based on (1)H NMR titration. Due to the intrinsic chirality of the receptors, their binding properties versus chiral dicarboxylic acid have been examined. The enantioselective binding of N-carbobenzyloxy protected L and D-glutamic acid due to additional pi-pi interactions of the protecting group with the receptor's framework is reported for [12](2)(-) in methylene chloride. For comparison, the association constants of receptor [12](2)(-) with a Boc protected L-glutamic acid and the racemic mixture of N-carbobenzyloxy protected glutamic acid have been determined.

Higher-order cycloaddition reactions in natural product synthesis

Abstract

Transition metal template controlled cycloaddition reactions. An efficient chromium(0)-mediated [6.pi. + 2.pi.] cycloaddition

Transition metal template controlled cycloaddition reactions. An efficient chromium(0)-mediated [6.pi. + 2.pi.] cycloaddition

Novel cyclization reactions on transition metal templates. The catalysis of intramolecular [4+2] cycloadditions by low-valent rhodium complexes

Novel cyclization reactions on transition metal templates. The catalysis of intramolecular [4+2] cycloadditions by low-valent rhodium complexes

ChemInform Abstract: Transition Metal Templates as Guides for Cyclizations

ChemInformVolume 20, Issue 45 Reviews ChemInform Abstract: Transition Metal Templates as Guides for Cyclizations B. M. TROST, B. M. TROST Dep. Chem., Stanford Univ., Stanford, CA 94305, USASearch for more papers by this author B. M. TROST, B. M. TROST Dep. Chem., Stanford Univ., Stanford, CA 94305, USASearch for more papers by this author First published: November 7, 1989 https://doi.org/10.1002/chin.198945367Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume20, Issue45November 7, 1989 RelatedInformation