Multi-Stimuli-Responsive Network of Multicatalytic Reactions using a Single Palladium/Platinum Catalyst.

Given her unrivalled proficiency in the synthesis of all molecules of life, nature has been an endless source of inspiration for developing new strategies in organic chemistry and catalysis. However, one feature that remains beyond chemists' grasp is her unique ability to adapt the productivity of metabolic processes in response to triggers that indicate the temporary need for specific metabolites. To demonstrate the remarkable potential of such stimuli-responsive systems, we present a metabolism-inspired network of multicatalytic processes capable of selectively synthesising a range of products from simple starting materials. Specifically, the network is built of four classes of distinct catalytic reactions - cross-couplings, substitutions, additions, and reductions, involving three organic starting materials - terminal alkyne, aryl iodide, and hydrosilane. All starting materials are either introduced sequentially or added to the system at the same time, with no continuous influx of reagents or efflux of products. All processes in the system are catalysed by a multifunctional heteronuclear PdII/PtII complex, whose performance can be controlled by specific additives and external stimuli. The reaction network exhibits a substantial degree of orthogonality between different pathways, enabling the controllable synthesis of ten distinct products with high efficiency and selectivity through simultaneous triggering and suppression mechanisms.

Chiral Supramolecular Polymers Assembled from Conformationally Flexible Amino-Acid-Substituted Biphenyldiimides.

Hydrogen-bonded polymers are a class of highly dynamic supramolecular aggregates, whose self-assembly may be tuned by very mild external or internal stimuli. However, the rational design of chiral supramolecules remains challenging especially when flexible components are involved. The combination of the inherent weakness and dynamic nature of the intermolecular bonds that hold together such assemblies with unrestricted molecular motions introduces additional factors which may affect the self-assembly process. In this report, the self-assembly of four amino acid-derived chiral biphenyldiimides into open-chain 1D supramolecular polymers is presented. While the primary driving force, COOH···HOOC hydrogen bonding, is responsible for the polymer growth in all cases, the amino acid side chains play an important role in either stabilizing or destabilizing the assemblies obtained, as deduced from studies of the thermodynamics of the self-assembly process. Furthermore, substantial differences in the structural factors governing the polymerization process between dynamic liquid and static solid are found. This work demonstrates the potential of the rather unexplored class of diimide-based organic dyes in the formation of well-organized chiral supramolecular assemblies with tunable properties.

Dynamic Cages-Towards Nanostructured Smart Materials.

The interest in capsular assemblies such as dynamic organic and coordination cages has blossomed over the last decade. Given their chemical and structural variability, these systems have found applications in diverse fields of research, including energy conversion and storage, catalysis, separation, molecular recognition, and live-cell imaging. In the exploration of the potential of these discrete architectures, they are increasingly being employed in the formation of more complex systems and smart materials. This Review highlights the most promising pathways to overcome common drawbacks of cage systems (stability, recovery) and discusses the most promising strategies for their hybridization with systems featuring various dimensionalities. Following the description of the most recent advances in the fabrication of zero to three-dimensional cage-based systems, this Review will provide the reader with the structure-dependent relationship between the employed cages and the properties of the materials.

Grid-Type Quaternary Metallosupramolecular Compounds Inhibit Human Cholinesterases through Dynamic Multivalent Interactions.

We report the implementation of coordination complexes containing two types of cationic moieties, i. e. pyridinium and ammonium quaternary salt, as potential inhibitors of human cholinesterase enzymes. Utilization of ligands containing NNO-coordination site and binding zinc metal ion allowed mono- and tetra-nuclear complexes to be obtained with corner and grid structural type, respectively, thus affecting the overall charge of the compounds (from +1 to +8). We were able to examine for the first time the multivalency effect of metallosupramolecular species on their inhibitory abilities towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Importantly, resolution of the crystal structures of the obtained enzyme-substrate complexes provided a better understanding of the inhibition process at the molecular level.

Pd(II) Complexes with Pyridine Ligands: Substituent Effects on the NMR Data, Crystal Structures, and Catalytic Activity.

A wide range of functionalized pyridine ligands have been employed to synthesize a variety of Pd(II) complexes of the general formulas [PdL4](NO3)2 and [PdL2Y2], where L = 4-X-py and Y = Cl- or NO3-. Their structures have been unambiguously established via analytical and spectroscopic methods in solution (NMR spectroscopy and mass spectrometry) as well as in the solid state (X-ray diffraction). This in-depth characterization has shown that the functionalization of ligand molecules with groups of either electron-withdrawing or -donating nature (EWG and EDG) results in significant changes in the physicochemical properties of the desired coordination compounds. Downfield shifts of signals in the 1H NMR spectra were observed upon coordination within and across the complex families, clearly indicating the relationship between NMR chemical shifts and the ligand basicity as estimated from pKa values. A detailed crystallographic study has revealed the operation of a variety of weak interactions, which may be factors explaining aspects of the solution chemistry of the complexes. The Pd(II) complexes have been found to be efficient and versatile precatalysts in Suzuki-Miyaura and Heck cross-coupling reactions within a scope of structurally distinct substrates, and factors have been identified that have contributed to efficiency improvement in both processes.

Charge Neutral [Cu2L2] and [Pd2L2] Metallocycles: Self-Assembly, Aggregation, and Catalysis.

A range of morphologically distinct metallosupramolecular Cu(II) and Pd(II) complexes has been constructed, based on the tritopic ligand 1,1',1″-(benzene-1,3,5-triyl)tris(4,4-dimethylpentane-1,3-dione) (H3L). By control of the reaction conditions, it is possible to generate distinct coordination assemblies possessing either macrocyclic or polymeric structures and more importantly distinct activity in catalysis of the Suzuki-Miyaura cross-coupling.

Hydrogen Bonding Directed Self-Assembly of a Binuclear Ag(I) Metallacycle into a 1D Supramolecular Polymer.

An Ag(I) metallacycle obtained unexpectedly during the preparation of Pd(II) complexes of the bifunctional ligand 5-([2,2'-bipyridin]-5-yl)pyrimidine-2-amine (L) has been characterized using X-ray structure determination as a binuclear, metallacyclic species [Ag2L2](SbF6)2, where both the bipyridine and pyrimidine-N donors of L are involved in coordination to the metal. The full coordination environment of the Ag(I) defines a case of highly irregular 4-coordination. In the crystal, the Ag-metallacycles assemble into one-dimensional supramolecular metalladynamers linked together by hydrogen-bonding interactions.

Dynamer and Metallodynamer Interconversion: An Alternative View to Metal Ion Complexation.

A bifunctional molecule containing both a bidentate binding site for metal ions and an aminopyrimidine H-bond donor-acceptor site has been synthesized, and its properties, in its free and coordinated forms, have been established in solution and in the solid state by analytical and spectroscopic methods as well as by X-ray structure determinations. Structural characterization has shown that it forms a one-dimensional H-bonded polymeric assembly in the solid state, while spectroscopic measurements indicate that it also aggregates in solution. The reaction of a simple Fe(II) salt with this assembly results in the emergence of two geometrical isomers of the complex: [FeL3](BF4)2·9H2O-C1 (meridional, mer) and [FeL3]2(SiF6)(BF4)2·12H2O-C2 (facial, fac). While, complex C1 in the solid state generates a one-dimensional H-bonded polymer involving just two ligands on each Fe center, with the chirality of the complex units alternating along the polymer chain, the structure of complex C2 shows NH···N interactions seen in both the ligand and mer complex (C1) structures to be completely absent. Physicochemical properties of the free and complexed ligand differ substantially.

Intrinsic Effect of Pyridine-N-Position on Structural Properties of Cu-Based Low-Dimensional Coordination Frameworks.

Metal-organic assemblies have received significant attention for catalytic and other applications, including gas and energy storage, due to their porosity and thermal/chemical stability. Here, we report the synthesis and physicochemical characterization of three metallosupramolecular assemblies consisting of isomeric ambidentate pyridyl-ß-diketonate ligands L1-L3 and Cu(II) metal ions. It has been demonstrated that the topology and dimensionality of generated supramolecular aggregates depend on the location of the pyridine nitrogen donor atom in L1-L3. This is seen in characterization of two distinct 2D polymeric assemblies, i.e., [Cu(L1)2]n and [Cu(L2)2]n, in which both ß-diketonate and pyridine groups are coordinated to the Cu(II) center, as well as in characterization of the mononuclear 1D complex Cu(L3)2, in which the central atom is bound only by two ß-diketonate units.

Dynamic Covalent Chemistry under High-Pressure:A New Route to Disulfide Metathesis.

This work describes, for the first time, the application of combined pressure and temperature stimuli in disulfide metathesis reactions. In the system studied, above a pressure of 0.2 GPa, equimolar amounts of symmetric disulfides bis 4-chlorophenyl disulfide [(4-ClPhS)2 ] and bis 2-nitrophenyl disulfide [(2-NO2 PhS)2 ] react to give the heterodimeric product 4-Cl-PhSSPh-2-NO2 . In contrast to experiments conducted in solution at atmospheric pressure or in mechanochemical experiments under ball-mill grinding conditions, there is no necessity to use a base or thiolate anion as a catalyst for the exchange reaction under investigated conditions. Single-crystal and powder X-ray diffraction revealed also that, despite the high-pressure conditions of this reaction, the heterodimeric-disulfide product unexpectedly crystallizes into the low-density polymorph A. This counterintuitive result contrasts with the high-pressure stability of the higher-density polymorph B, confirmed by its compression up to 2.8 GPa with no signs of a phase transition.

Switching Multivalent DNA Complexation using Metal-Controlled Cationic Supramolecular Self-Assemblies.

We provide a proof-of-principle that coordination chemistry drives the in situ self-assembly of an inactive ligand into a multivalent cluster capable of effectively complexing DNA. We show that metal coordination and scavenging can be used to switch the multivalency of the system. Thus, controlled DNA complexation and decomplexation could be achieved.

Multivalent Metallosupramolecular Assemblies as Effective DNA Binding Agents.

We report the implementation of coordination chemistry onto the generation of new types of metallosupramolecular complexes with laterally appended cationic moieties for DNA binding in buffered aqueous media. Utilization of an N,N,O-type coordination pocket along with an octahedral zinc(II) metal ion allowed us to obtain mono- and tetranuclear complexes in both solution and solid state, as confirmed by NMR spectroscopy and single-crystal X-ray diffraction, respectively. By using isothermal titration calorimetry and gel electrophoresis, multiply charged cationic assemblies were observed to effectively bind to DNA through multivalent electrostatic interactions. Furthermore, we observed a correlation between the multivalency of the compounds employed and the effectiveness of DNA binding.

pH-Induced Linkage Isomerism of Pd(II) Complexes: A Pathway to Air- and Water-Stable Suzuki-Miyaura-Reaction Catalysts.

The Pd(II) complexes of the ambidentate pyridyldiketones 2,2-dimethyl-5-(3- or 4-pyridyl)pentane-3,5-dione are readily prepared in their linkage isomeric forms by the appropriate pH control during syntheses. The isolated diketonate- or pyridine-bound species can be interconverted with essentially 100% efficiency by treatment with an acid or base, respectively. Under the normal basic conditions for a Suzuki-Miyaura coupling, only the diketonate forms are present and act as very efficient catalysts for this reaction. The dynamic nature of the presented complexes allows the catalytic process to be quenched and reactivated at any stage without the risk of losing the catalyst's activity.

Quaterpyridines as Scaffolds for Functional Metallosupramolecular Materials.

Quaterpyridine (qtpy) ligands have found significant applications as N-heterocyclic scaffolds in self-assembly processes, in particular the formation of various metallosupramolecular architectures, limited, however, by difficulties in their synthesis. Recent progress in the preparative organic and organometallic chemistry of polypyridines has resulted in the elimination of the most serious drawbacks concerning qtpy synthesis, consequently giving rise to a renewed interest in this class of compounds. Herein, we endeavor to define the essential aspects of quaterpyridine chemistry and provide the reader with a perspective on the ways in which this field has begun to flourish.

Generation of Multicomponent Molecular Cages using Simultaneous Dynamic Covalent Reactions.

Cage compounds are very attractive structures for a wide range of applications and there is ongoing interest in finding effective ways to access such kinds of complex structures, particularly those possessing dynamic adaptive features. Here we report the accessible synthesis of new type of organic cage architectures, possessing two different dynamic bonds within one structure: hydrazones and disulfides. Implementation of three distinct functional groups (thiols, aldehydes and hydrazides) in the structure of two simple building blocks resulted in their spontaneous and selective self-assembly into aromatic cage-type architectures. These organic cages contain up to ten components linked together by twelve reversible covalent bonds. The advantage provided by the presented approach is that these cage structures can adaptively self-sort from a complex virtual mixture of polymers or macrocycles and that dynamic covalent chemistry enables their deliberate disassembly through controlled component exchange.

Surface Trapping and STM Observation of Conformational Isomers of a Bis(Terpyridine) Ligand from Metallosupramolecular Grids.

Tetranuclear Co-grid complexes incorporating bis-tridentate ligands, namely 4,6-bis(2,2'-bipyrid-6-yl)-2-phenylpyrimidine, were electrosprayed onto a Au(111) substrate under an ultrahigh vacuum. Fragmentation occurs leaving the ligands in four different conformations. Most ligands are found to form H-bonded dimers. The most abundant conformer of the ligand on the Au surface is an asymmetric form, which has not been observed before. The present results indicate that the fragmentation of coordination compounds during the deposition process, in principle, allows for surface trapping, identification, and investigation of high energy, out-of-equilibrium conformations of the ligand molecules at low temperatures, which otherwise would not be observable.

Disulfide exchange: exposing supramolecular reactivity through dynamic covalent chemistry.

A Tutorial Review of the subtle supramolecular interactions influencing the outcomes of equilibrating systems, focusing on the dynamic covalent chemistry (DCC) of disulfide exchange reactions, is presented. We discuss the topics of cation-π interactions (2.1), hydrophobic effects (2.2), hydrogen bonding interactions (2.3) aromatic donor-acceptor interactions (2.4), and metal-ligand interactions (2.5) in the context of dynamic disulfide chemistry.

Generation of a Multicomponent Library of Disulfide Donor-Acceptor Architectures Using Dynamic Combinatorial Chemistry.

We describe here the generation of new donor-acceptor disulfide architectures obtained in aqueous solution at physiological pH. The application of a dynamic combinatorial chemistry approach allowed us to generate a large number of new disulfide macrocyclic architectures together with a new type of [2]catenanes consisting of four distinct components. Up to fifteen types of structurally-distinct dynamic architectures have been generated through one-pot disulfide exchange reactions between four thiol-functionalized aqueous components. The distribution of disulfide products formed was found to be strongly dependent on the structural features of the thiol components employed. This work not only constitutes a success in the synthesis of topologically- and morphologically-complex targets, but it may also open new horizons for the use of this methodology in the construction of molecular machines.

Guest-induced transformation of a porphyrin-edged Fe(II)4L6 capsule into a Cu(I)Fe(II)2L4 fullerene receptor.

The combination of a bent diamino(nickel(II) porphyrin) with 2-formylpyridine and Fe(II) yielded an Fe(II) 4 L6 cage. Upon treatment with the fullerenes C60 or C70 , this cage was found to transform into a new host-guest complex incorporating three Fe(II) centers and four porphyrin ligands, in an arrangement that is hypothesized to maximize π interactions between the porphyrin units of the host and the fullerene guest bound within its central cavity. The new complex shows coordinative unsaturation at one of the Fe(II) centers as the result of the incommensurate metal-to-ligand ratio, which enabled the preparation of a heterometallic cone-shaped Cu(I) Fe(II) 2 L4 adduct of C60 or C70 .

Dynamic covalent synthesis.

Dynamic covalent synthesis aims to precisely control the assembly of simple building blocks linked by reversible covalent bonds to generate a single, structurally complex, product. In recent years, considerable progress in the programmability of dynamic covalent systems has enabled easy access to a broad range of assemblies, including macrocycles, shape-persistent cages, unconventional foldamers and mechanically-interlocked species (catenanes, knots, etc.). The reversibility of the covalent linkages can be either switched off to yield stable, isolable products or activated by specific physico-chemical stimuli, allowing the assemblies to adapt and respond to environmental changes in a controlled manner. This activatable dynamic property makes dynamic covalent assemblies particularly attractive for the design of complex matter, smart chemical systems, out-of-equilibrium systems, and molecular devices.