The effect of ionic versus covalent functionalization of polyoxometalate hybrid materials with coordinating subunits on their stability and interaction with DNA.

Inorganic-organic hybrid materials that combine both Polyoxometalates (POMs) and metal ion coordinating subunits (CSUs) represent promising multifunctional materials. Though their individual components are often biologically active, utilization of hybrid materials in bioassays significantly depends on the functionalization method and thus resulting stability of the system. Quite intriguingly, these aspects were very scarcely studied in hybrid materials based on the Wells-Dawson POM (WD POM) scaffold and remain unknown. We chose two model WD POM hybrid systems to establish how the functionalization mode (ionic vs. covalent) affects their stability in biological medium and interaction with nucleic acids. The synthetic scope and limitations of the covalent POM-terpyridine hybrids were demonstrated and compared with the ionic Complex-Decorated Surfactant Encapsulated-Clusters (CD-SECs) hybrids. The nature of POM and CSU binding can be utilized to modulate the stability of the hybrid and the extent of DNA binding. The above systems show potential to behave as model cargo-platforms for potential utilization in medicine and pharmacy.

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.

Simultaneous Formation of a Fully Organic Triply Dynamic Combinatorial Library.

Here we report the simultaneous formation of doubly and triply dynamic libraries as a result of exchange reactions between functionalized organic building blocks. A combination of three different reversible covalent linkages involving a boronate ester transesterification along with an imine and disulfide exchange was employed to generate a new type of fully organic triply dynamic molecular assembly.

Complex-decorated surfactant-encapsulated clusters (CD-SECs) as novel multidynamic hybrid materials.

Generation of well-defined organic-inorganic hybrid materials with controllable size and morphology is challenging and an active area of modern research in view of their unique properties and thus multifunctional applications. Specifically polyoxometalates (POMs) were recognized as a very promising group for the construction of those systems, nonetheless there are domains where the profound understanding of hierarchical mutual interactions and assembly are lacking. We present an efficient approach towards the synthesis of a novel group of POM-based nanocomposites that we name Complex-Decorated Surfactant Encapsulated-Clusters (CD-SECs). In the investigated system the organic surfactant may behave as a metal-coordinating agent, thus allowing for derivatization of the synthesized SECs via utilization of the non-covalent interactions. We demonstrate possibilities and limitations of three types of hybrid systems (H1-H3) generated via seven distinct constructing approaches (routes A-G). These systems have the potential to exhibit multiresponsive functions depending on the nature of their building blocks and could find many potential applications in biology or materials science.

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.

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.

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.

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.