Coordination-Directed Construction of Molecular Links.

Since the emergence of the concept of chemical topology, interlocked molecular assemblies have graduated from academic curiosities and poorly defined species to become synthetic realities. Coordination-directed synthesis provides powerful, diverse, and increasingly sophisticated protocols for accessing interlocked molecules. Originally, metal ions were employed solely as templates to gather and position building blocks in entwined or threaded arrangements. Recently, metal centers have increasingly featured within the backbones of the integral structural elements, which in turn use noncovalent interactions to self-assemble into intricate topologies. By outlining ingenious recent examples as well as seminal classic cases, this Review focuses on the role of metal-ligand paradigms in assembling molecular links. In addition, the ever-evolving approaches to efficient assembly, the structural features of the resulting architectures, and their prospects for the future are also presented.

Reversible Structural Transformation between a Molecular Solomon Link and an Unusual Unsymmetrical Trefoil Knot.

A template-free Cp*Ir-based molecular Solomon link and an unusual trefoil knot induced by stacking interactions were realized via selection of the nonrigid dipyridyl ligand 4,4'-bis(pyridin-4-ylmethyl)-1,1'-biphenyl (BpmBp). In addition, a novel heterobimetallic tetranuclear (IrIII2 + AgI2) complex featuring argentophilic interaction was synthesized in high yield. Remarkably, the reversible topological transformation between the Solomon link and an unusual trefoil knot can be achieved by utilizing the chemical reactivity of silver(I) ions under mild conditions, as demonstrated by a detailed X-ray crystallographic study.

Dynamic Interconversion between Solomon Link and Trapezoidal Metallacycle Ensembles Accompanying Conformational Change of the Linker.

A novel template-free Cp*Rh-based molecular Solomon link has been established through selection of the flexible ligand L as a linker and the half-sandwich rhodium(III) dinuclear fragment B1 as a rigid capping unit. Furthermore, we demonstrate that the self-assembly of the Solomon link based on the flexible ligand is both solvent- and concentration-dependent: the Solomon link is formed in concentrated methanolic solutions, whereas formation of a dinuclear trapezoidal rectangle is favored at low concentrations or in acetonitrile or DMF solutions. Remarkably, alteration of the solvent or concentration can promote a unique and dynamic interconversion between the two molecular species, accompanying conformational change of the ligand. The synthetic outcomes are supported by single-crystal X-ray diffraction analysis.

Sanjin tablets for acute uncomplicated lower urinary tract infection (syndrome of dampness-heat in the lower jiao): protocol for randomized, double-blind, double-dummy, parallel control of positive drug, multicenter clinical trial.

BACKGROUND: Acute uncomplicated lower urinary tract infection (UTI) is one of the most common bacterial infections. Patients usually present with dysuria, urinary urgency, urinary frequency, and suprapubic pain or tenderness. Approximately 150 million people are diagnosed with UTI each year worldwide. The high recurrence rate of lower UTI is a common problem of clinical treatment. The misuse of antibiotics has led to the emergence of a number of resistant bacterial strains. Thus, traditional Chinese medicine is considered as an alternative option for treating acute uncomplicated lower UTI. Thus, this study aims to evaluate the efficacy and safety of Sanjin tablets (SJT) for the treatment of acute uncomplicated lower UTI, explore whether SJT can reduce or substitute the use of antibiotics, and reduce the recurrence rate in the treatment of acute uncomplicated lower UTI. METHODS/DESIGN: In this study, a randomized, double-blind, double-dummy, parallel control of positive drug, multicenter clinical study will be established. A total of 252 patients with acute uncomplicated lower UTI (syndrome of dampness-heat in the lower jiao) will be randomly allocated in the ratio of 1:1:1 to three groups: experimental group; control group 1; and control group 2. The experimental group receives Sanjin tablets plus levofloxacin tablets (LT) placebo; the control group 1 receives LT plus SJT placebo; and the control group 2 receives SJT plus LT on the first five days, SJT plus LT placebo on the last two days. Each group will be treated for seven days and followed-up 1-2 times. The primary outcome measures of effective rate and recurrence rate are symptoms. Secondary outcome measures of effective rate and recurrence rate are the urine leukocytes, bacteriology examination, and safety assessment. Outcomes will be assessed at baseline and after treatment. DISCUSSION: This study protocol will provide the research data of efficacy and safety of SJT for the treatment of acute uncomplicated lower UTI. The first aim is to determine whether Sanjin tablets can reduce the use of antibiotics; the second aim is to determine whether Sanjin tablets can substitute the use of antibiotics. The recurrence rate will be assessed after cured to determine whether SJT can reduce the recurrence rate. The results of this study will improve the rational use of drugs, especially the rational application of antibiotics. It will also enable safety evaluation from laboratory indices and adverse events, which will provide reliable evidence for clinical treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03658291 . Registered on 4 September 2018.

Selective Synthesis of Discrete Mono-, Interlocked-, and Borromean Ring Ensembles Based on a π-Electron-Deficient Ligand.

Herein, we present a new synthetic approach to achieve selective supramolecular transformations and construct different interlocked metallacycles featuring a π-electron-deficient thiazolo[5,4-d]thiazole-derived ligand. We demonstrate that the formation of mono-rings, interlocked rings ([2]catenanes) and Borromean rings can be controlled by adjusting the length of the binuclear half-sandwich RhIII and IrIII building blocks. Furthermore, a concentration effect or D-A stacking interaction between the pyrene guest and the thiazolo[5,4-d]thiazole-based ligand promotes a unique and reversible conversion between catenane structures and metalla-rectangles. The synthetic results are supported by single-crystal X-ray diffraction analysis.

Covalent Post-assembly Modification Triggers Structural Transformations of Borromean Rings.

A series of supramolecular transformation cascades are presented here, employing ligand exchange reactions, concentration-dependent Borromean ring (BR) linking and unlinking, and inverse electron-demand Diels-Alder (IEDDA) reactions. The new family of template-free, tetrazine-edged BRs are constructed by using ligand exchange reactions, and their concentration-dependent linking and unlinking reactions have been observed. Moreover, Borromean precursors have been demonstrated to further undergo supramolecular structural transformations induced by rapid and efficient IEDDA reactions to afford corresponding post-assembly modified architectures. Remarkably, subtle steric increases of the pyridazine fragments obtained by IEDDA reactions is regarded to induce controlled topological transformations in the cascade, unlinking the Borromean structures by using electron-rich dienophiles as triggering signals.

Selective Encapsulation and Separation of Dihalobenzene Isomers with Discrete Heterometallic Macrocages.

A series of metallosupramolecular architectures have been prepared, including rectangles, prisms and cages, that feature half-sandwich rhodium(III) fragments at the vertices. Remarkably, a stable cage-like heteropolymetallic complex possessing eight rhodium(III) and two silver(I) metal ions (3) has been obtained following a multistep procedure. The RhIII /AgI mixed macrocage enables the separation of dihalogenated benzene derivatives with high selectivity. Furthermore, a detailed X-ray crystallographic study confirmed that the discriminative encapsulation of para-dihalobenzene (dichlorobenzene, dibromobenzene and diiodobenzene) is favored by Ag-π interactions and steric effects.

Preparation of polynuclear NHC complexes by post-synthetic modification of half-sandwich rhodium and iridium complexes bearing C-azolato ligands.

A series of bimetallic and trimetallic complexes has been prepared by N-alkylation of mononuclear half-sandwich rhodium and iridium di-NHC complexes featuring bidentate chelate ligands composed of a classical NHC and a C-azolato donor. The shape and the separation between metal centers in the obtained complexes are highly dependent on the alkylating agent used. While the polynuclear complexes were formed as diastereomeric mixtures according to NMR spectroscopy, X-ray diffraction analysis revealed their remarkable preference to crystallize as meso compounds. The reactivity of the bimetallic, olefin-bridged complexes in electrophilic addition reactions has been investigated.

Construction of half-sandwich multinuclear complexes including tunnel architectures via C-H-activation-directed assembly.

Three aromatic ligands containing carboxyl- or nitrogen-substituted groups were employed in the construction of half-sandwich complexes via C-H activation-directed assembly, leading to the construction of eleven multinuclear organometallic iridium or rhodium complexes, including those of bi-, tetra-, hexa- and octanuclear, under mild conditions, with the help of N-donor linkers. These complexes were characterized by proton NMR, IR spectroscopy, elemental analysis, electrospray ionization (ESI) mass spectrometry and single-crystal X-ray diffraction analysis. In these complexes, two complexes were observed to exist as isomers, and several racemic enantiomers can be found. X-ray crystal structure determinations show that a series of supramolecular tunnel architectures are formed by stacking through hydrogen-bond interactions, and solvent or trifluoromethylsulfonate anion guests were found to be located in certain parts of the channels. This work represents the first successful construction of octanuclear half-sandwich complexes based on the cleavage of C-H bonds.

Light-initiated reversible conversion of macrocyclic endoperoxides derived from half-sandwich rhodium-based metallarectangles.

Although reversible photo-dimerization or oxygenation of anthracene and its derivatives is a common reaction, light-initiated reversible conversion of endoperoxide organometallic frameworks has only rarely been addressed. Herein, a series of tetranuclear organometallic macrocycles, [Cp*2Rh2(µ-C2O4-κO)]2(BP4VA)2(OTf)4 (4), [Cp*2Rh2(BiBzIm)]2(BP4VA)2(OTf)4 (5), and [Cp*2Rh2(DHBQ)]2(BP4VA)2(OTf)4 (6), were obtained in good yields from the reactions of the binuclear half-sandwich rhodium precursors [Cp*2Rh2(µ-C2O4-κO)Cl2] (1), [Cp*2Rh2(BiBzIm)Cl2] (2), and [Cp*2Rh2(DHBQ)Cl2] (3) with the 9,10-bis((E)-2-(pyrid-4-yl)vinyl)anthracene (BP4VA) ligand. The photochemical reaction of these metallarectangles was investigated by NMR and UV/vis spectroscopy. We have demonstrated that complexes 4, 5, and 6 can be reversibly and nearly quantitatively converted to the macrocyclic endoperoxides 4-O2, 5-O2, and 6-O2. Meanwhile, the structure of the endoperoxide photoproducts was unambiguously confirmed by 1H/13C NMR spectroscopy, IR spectroscopy, elemental analyses, and X-ray crystallography.

Stacking-interaction-induced host-guest chemistry and Borromean rings based on a polypyridyl ligand.

Template-free molecular Borromean rings (BRs) and open-ended molecular capsules were realized by strategic selection of the polypyridyl ligand tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j] phenazine (TPPHZ) with a large surface area and specific geometry. The topology of these intricate architectures was constructed via precisely controlled stacking interactions, as evidenced from single-crystal X-ray analysis.

Stepwise construction of discrete parallelogram- and prism-shaped organometallic architectures based on half-sandwich rhodium fragments.

Herein we describe how to take advantage of a multifunctional ligand to conveniently control the shapes and sizes of different types of discrete organometallic assemblies. Using a versatile ligand 2-(pyridin-2-yl)-1H-imidazole-4,5-dicarboxylate (HL2-), which features three kinds of chelating sites, together with half-sandwich rhodium fragments, a series of discrete organometallic complexes with tetranuclear parallelogram and hexanuclear trigonal prism shapes were achieved. The isomerization of the hexanuclear assemblies was confirmed by single-crystal X-ray diffraction analysis. The results also reiterate that pyridyl-substituted imidazole-4,5-dicarboxylate ligands can be used as multifunctional organic scaffolds in the construction of elegant architectures.

Syntheses, Structures, and Solution Studies of Multicomponent Macrocycles and Cages Based on Versatile Ligands.

Different types of multinuclear half-sandwich rhodium macrocycles and cages were designed and synthesized by using two similar multifunctional hydroxamate ligands (pyrazine-2-hydroxamic acid (NaHL1 ) and 4,4'-bipyridine-2-hydroxamic acid (KHL2 )) featuring one monodentate site and two pairs of chelating sites. The RhIII -PdII heterometallic macrocycles were constructed by using the semi-open palladium(II) source [Pd(en)Cl2 ] with two free acceptor sites. However, only one kind of macrocycle was found when the shorter ligand L1 was used, while in for the larger ligand, various spectroscopic techniques demonstrated the coexistence of hexanuclear and octanuclear macrocycles in solution and the proportions of both components depended on concentration and temperature. The palladium salt Pd(NO3 )2 , as a source of "naked" Pd2+ , was introduced to assemble the cuboid-shaped cage composed of two types of metal ions and three types of organic ligands. In addition, two silver(I)-containing mixed-metal complexes bridged by pyrazine were obtained, in which two forms of decanuclear complex with C2v and C2h point symmetry cocrystallized-one is a polymeric structure and the other is a discrete cage. However, the third form, with D2 point symmetry, was found in the larger cage.