Photocycloaddition as a Tool for Modulation of the Lower Critical Solution Temperature in a Molecular π-System to Control Transmission of Solar Radiation.

Diels-Alder photocycloaddition, a well-known textbook reaction, has not been explored in materials chemistry. Herein we describe how this classical photochemistry can be used to modulate the lower critical solution temperature (LCST) of a molecular π-system, which can further be exploited for the controlled transmission of solar radiation for the management of indoor heat and light. An amphiphilic anthracene derivative 9-PA-1 exhibited LCST behavior at 27-32 °C with a reversible transition from a transparent to an opaque phase in water (1-5 mM). Irradiation of a toluene solution of 9-PA-1 with 365 nm light resulted in a [4+2] photocycloadduct 9-PA-2, which exhibited a modulated LCST behavior at 25-27 °C, at a concentration as low as 6 µM. The photocycloaddition of 9-PA-1 was significantly retarded in water, making it a stable candidate for the design of sustainable smart windows. We also demonstrated 100 cm2 smart window prototypes (ΔTlum 82 %, ΔTIR 68 %, ΔTsol 73 %) with more than 1000 cycles of stable operation.

Tunable Capacitive Behavior in Metallopolymer-based Electrochromic Thin Film Supercapacitors.

Volumetric capacitance is a more critical performance parameter for rechargeable power supply in lightweight and microelectronic devices as compared to gravimetric capacitance in larger devices. To this end, we report three electrochromic metallopolymer-based electrode materials containing Fe2+ as the coordinating metal ion with high volumetric capacitance and energy densities in a symmetric two-electrode supercapacitor setup. These metallopolymers exhibited volumetric capacitance up to 866.2 F cm-3 at a constant current density of 0.25 A g-1. The volumetric capacitance (poly-Fe-L2: 544.6 F cm-3 > poly-Fe-L1: 313.8 F cm-3 > poly-Fe-L3: 230.8 F cm-3 at 1 A g-1) and energy densities (poly-Fe-L2: 75.5 mWh cm-3 > poly-Fe-L1: 43.6 mWh cm-3 > poly-Fe-L3: 31.2 mWh cm-3) followed the order of the electrical conductivity of the metallopolymers and are among the best values reported for metal-organic systems. The variation in the ligand structure was key toward achieving different electrical conductivities in these metallopolymers with excellent operational stability under continuous cycling. High volumetric capacitances and energy densities combined with tunable electro-optical properties and electrochromic behavior of these metallopolymers are expected to contribute to high performance and compact microenergy storage systems. We envision that the integration of smart functionalities with thin film supercapacitors would warrant the surge of miniaturized on-chip microsupercapacitors integrated in-plane with other microelectronic devices for wearable applications.

Ligand-Controlled Electrochromic Diversification with Multilayer Coated Metallosupramolecular Polymer Assemblies.

Designing surface-confined molecular systems capable of expressing changes in functional properties as a result of slight variations in chemical structure under the influence of an external stimulus is of contemporary interest. In this context, we have designed three tetraterpyridine ligands with variations in their core architecture (phenyl vs tetraphenylethynyl vs bithiophene) to create spray-coated electrochromic assemblies of iron(II)-based metallosupramolecular polymer network films on transparent conducting oxide substrates. These assemblies exhibited molecular permeability and spectroelectrochemical properties that are in turn dictated by the ligand structure. Electrochromic films with high coloration efficiencies (up to 1050 cm2/C) and superior optical contrast (up to 76%) with a concomitant color-to-color redox transition were readily achieved. These functional switching elements were integrated into sandwich-type electrochromic cells (CE up to 641 cm2/C) that exhibited high contrast ratios of up to 56%, with attractive ON-OFF ratios, fast switching kinetics, and high operational stability. Every measurable spectroelectrochemical property of the films and devices is an associated function of the ligand structure that coordinates the same metal ion to different extents. While exhibiting a ligand-structure induced differential metal coordination leading to porosity and spectroelectrochemical diversification, these assemblies allow the creation of electrochromic patterns and images by a simple spray-coating technique.

Thermochromic Color Switching to Temperature Controlled Volatile Memory and Counter Operations with Metal-Organic Complexes and Hybrid Gels.

Temperature is often not considered as a precision stimulus for artificial chemical systems in contrast to the host-guest interactions related to many natural processes. Similarly, mimicking multi-state volatile memory operations using a single molecular system with temperature as a precision stimulus is highly laborious. Here we demonstrate how a mixture of iron(II) chloride and bipyridine can be used as a reversible color-to-colorless thermochromic switch and logic operators. The generality of the approach was illustrated using CoII and NiII salts that resulted in color-to-color transitions. DMSO gels of these systems, exhibited reversible opaque-transparency switching. More importantly, optically readable multi-state volatile memory with temperature as a precision input has been demonstrated. The stored data is volatile and is lost instantaneously upon withdrawal or change of temperature. Simultaneous read-out at multiple wavelengths results in single-input/multi-output sequential logic operations such as data accumulators (counters) leading to volatile memory states. The present system provides access to thermoresponsive materials wherein temperature can be used as a precision stimulus.

Light-controlled switching of the spin state of iron(III).

Controlled switching of the spin state of transition metal ions, particularly of FeII and FeIII, is a prerequisite to achieve selectivity, efficiency, and catalysis in a number of metalloenzymes. Here we report on an iron(III) porphyrin with a photochromic axial ligand which, upon irradiation with two different wavelengths reversibly switches its spin state between low-spin (S = 1/2) and high-spin (S = 5/2) in solution (DMSO-acetone, 2:598). The switching efficiency is 76% at room temperature. The system is neither oxygen nor water sensitive, and no fatigue was observed after more than 1000 switching cycles. Concomitant with the spin-flip is a change in redox potential by ~60 mV. Besides serving as a simple model for the first step of the cytochrome P450 catalytic cycle, the spin switch can be used to switch the spin-lattice relaxation time T1 of the water protons by a factor of 15.

Tubular Hybrids: A Nanoparticle-Molecular Network.

We report here a new methodology for the formation of freestanding nanotubes composed of individual gold nanoparticles (NPs) cross-linked by coordination complexes or porphyrin molecules using WS2 nanotubes (INT-WS2) as a template. Our method consists of three steps: (i) coverage of these robust inorganic materials with monodispersed and dense monolayers of gold NPs, (ii) formation of a molecular AuNP network by exposing these decorated tubes to solutions containing a ruthenium polypyridyl complex or meso-tetra(4-pyridyl)porphyrin, and (iii) removal of the INT-WS2 template with a hydrogen peroxide solution. Nanoindentation of the template-free AuNP tubes with atomic force microscopy indicates a radial elastic modulus of 4 GPa. The template-free molecular AuNP tubes are characterized using scanning and transmission electron microscopy, energy-dispersive X-ray spectroscopy, and micro-Raman spectroscopy. The methodology provides a convenient and scalable strategy for the realization of molecular AuNP tubes with a defined length and diameter, depending on the dimensions of the template.

Electrochromic Metallo-Organic Nanoscale Films: Fabrication, Color Range, and Devices.

In this study, we demonstrate a versatile approach for the formation of electrochromic nanoscale assemblies on transparent conductive oxides on both rigid and flexible substrates. Our method is based on the application of alternating spin-coated layers of well-defined metal polypyridyl complexes and a palladium(II) salt to form electrochemically addressable films with a high chromophore density. By varying the central metal ion of the polypyridyl complexes (Os, Ru, and Fe) and their ligands and by mixing these complexes, coatings with a wide range of colors can be achieved. These coatings cover a large area of RGB color space. The coloration intensities of these nanoscale films can be tuned by the number of deposition steps. The materials have very attractive ON/OFF ratios, electrochemical stabilities, and coloration efficiencies. Reversible color-to-colorless and color-to-color transitions were demonstrated, and the films were further integrated into sandwich cells.

Gold Nanoparticle Assemblies on Surfaces: Reactivity Tuning through Capping-Layer and Cross-Linker Design.

The immobilization of metal nanoparticles (NPs) with molecular control over their organization is challenging. Herein, we report the formation of molecularly cross-linked AuNP assemblies using a layer-by-layer approach. We observed four types of assemblies: 1) small aggregates of individual AuNPs, 2) large aggregates of individual AuNPs, 3) networks of fused AuNPs, and 4) gold islands. Interestingly, these assemblies with the different cross-linkers and capping layers represent different stages in the complete fusion of AuNPs to afford islands of continuous gold. We demonstrate that the stability toward fusion of the nanoparticles of the on-surface structures can be controlled by the reactivity of the cross-linkers and the hydrophilicity/hydrophobicity of the nanoparticles.

Rerouting electron transfer in molecular assemblies by redox-pair matching.

We demonstrate how the distance over which electron transfer occurs through organic materials can be controlled and extended. Coating of conductive surfaces with nanoscale layers of redox-active metal complexes allows the electrochemical addressing of distant layers that are otherwise electrochemically silent. Our materials can pass electrons selectively in directions that are determined by positioning of layers of metal complexes and the distances between them. These electron-transfer processes can be made dominantly uni- or bidirectional. The design involves 1) a set of isostructural metal complexes with different electron affinities, 2) a scalable metal-organic spacer, and 3) a versatile assembly approach that allows systematic variation of composition, structure, and electron-transfer properties. We control the electrochemical communication between interfaces by the deposition sequence and the spacer length, therefore we are able to program the bulk properties of the assemblies.

Coordination-based molecular assemblies as electrochromic materials: ultra-high switching stability and coloration efficiencies.

We demonstrate high-performance electrochromic assemblies that exhibit a practical combination of low-voltage operation and efficient electrochromic switching as well as long-term thermal and redox stability (1.12 × 10(5) cycles). Our molecular assemblies can be integrated into a solid-state configuration. Furthermore, we also show how the molecular structure of the chromophores correlates with the materials' growth and function. The coloration efficiencies of our assemblies are higher than those of inorganic materials and many conducting polymers, in addition to offering an alternative fabrication approach.

Metal-organic microstructures: from rectangular to stellated and interpenetrating polyhedra.

Despite the tremendous progress made in the design of supramolecular and inorganic materials, it still remains a great challenge to obtain uniform structures with tailored size and shape. Metal-organic frameworks and infinite coordination polymers are examples of rapidly emerging materials with useful properties, yet limited morphological control. In this paper, we report the solvothermal synthesis of diverse metal-organic (sub)-microstructures with a high degree of uniformity. The porous and thermally robust monodisperse crystalline solids consist of tetrahedral polypyridyl ligands and nickel or copper ions. Our bottom-up approach demonstrates the direct assembly of these materials without the addition of any surfactants or modulators. Reaction parameters in combination with molecular structure encoding are the keys to size-shape control and structural uniformity of our metal-organic materials.

On-surface solvent-free crystal-to-co-crystal conversion by non-covalent interactions.

Enabling and understanding new methodologies to fabricate molecular assemblies driven by intermolecular interactions is fundamental in chemistry. Such forces can be used to control crystal growth and enable surface-confinement of these materials, which remains challenging. Here we demonstrate for the first time, a solvent-free on-surface crystal-to-co-crystal conversion process driven by halogen bonding (XB). By exposing a polycrystalline organic material, consisting of a XB-acceptor moiety, to the vapors of a complementary XB-donor compound, the corresponding halogen-bonded co-crystals were formed. Furthermore, we demonstrate that this approach can also be utilized for non-crystalline materials to afford surface-confined organic composites. Our stepwise vapor-based approach offers a new strategy for the formation of hybrid supramolecular materials.

Development of novel ADCs: conjugation of tubulysin analogues to trastuzumab monitored by dual radiolabeling.

Tubulysins are highly toxic tubulin-targeting agents with a narrow therapeutic window that are interesting for application in antibody-drug conjugates (ADC). For full control over drug-antibody ratio (DAR) and the effect thereof on pharmacokinetics and tumor targeting, a dual-labeling approach was developed, wherein the drug, tubulysin variants, and the antibody, the anti-HER2 monoclonal antibody (mAb) trastuzumab, are radiolabeled. (131)I-radioiodination of two synthetic tubulysin A analogues, the less potent TUB-OH (IC50 > 100 nmol/L) and the potent TUB-OMOM (IC50, ~1 nmol/L), and their direct covalent conjugation to (89)Zr-trastuzumab were established. Radioiodination of tubulysins was 92% to 98% efficient and conversion to N-hydroxysuccinimide (NHS) esters more than 99%; esters were isolated in an overall yield of 68% ± 5% with radiochemical purity of more than 99.5%. Conjugation of (131)I-tubulysin-NHS esters to (89)Zr-trastuzumab was 45% to 55% efficient, resulting in ADCs with 96% to 98% radiochemical purity after size-exclusion chromatography. ADCs were evaluated for their tumor-targeting potential and antitumor effects in nude mice with tumors that were sensitive or resistant to trastuzumab, using ado-trastuzumab emtansine as a reference. ADCs appeared stable in vivo. An average DAR of 2 and 4 conferred pharmacokinetics and tumor-targeting behavior similar to parental trastuzumab. Efficacy studies using single-dose TUB-OMOM-trastuzumab (DAR 4) showed dose-dependent antitumor effects, including complete tumor eradications in trastuzumab-sensitive tumors in vivo. TUB-OMOM-trastuzumab (60 mg/kg) displayed efficacy similar to ado-trastuzumab emtansine (15 mg/kg) yet more effective than trastuzumab. Our findings illustrate the potential of synthetic tubulysins in ADCs for cancer treatment.

Synthesis and structure-activity relationship studies of novel tubulysin U analogues--effect on cytotoxicity of structural variations in the tubuvaline fragment.

Tubulysins are cytotoxic natural products with promising anti-cancer properties, originally isolated from myxobacterial cultures. Structurally, tubulysins are tetrapeptides, incorporating three unusual (Mep, Tuv and Tup) and one proteinogenic amino acid (Ile). Here we describe the synthesis and structure-activity relationship studies of novel tubulysin U and V analogues, with variations in the central Tuv fragment, which is known to be of paramount importance for tubulysins' potency and hence cytotoxicity, but has seldom been modified in previous studies. Specifically, we replaced the natural iso-propyl and acetoxy functionalities with other structurally related groups. In general, the new analogues showed much lower potency relative to native tubulysin U. However, one of the synthetic analogues (1f) having a MOM function replacing the acetyl group exhibited a 22 nM IC50 on the HT-29 cell line which is comparable to the IC(50) displayed by tubulysin U (3.8 nM). Furthermore, the synthetic methodology reported herein was found to be flexible enough to deliver different core-modified tubulysin analogues and hence may be regarded as a scalable and convenient strategy for the chemical generation of novel tubulysin analogues.

The generation of "unnatural" products: synthetic biology meets synthetic chemistry.

Natural product analogue generation is important, providing tools for chemical biology, enabling structure activity relationship determination and insight into the way in which natural products interact with their target biomolecules. The generation of analogues is also often necessary in order to improve bioavailability and to fine tune compounds' activity. This review provides an overview of the catalogue of approaches available for accessing series of analogues. Over the last few years there have been major advances in genome sequencing and the development of tools for biosynthetic pathway engineering; it is therefore becoming increasingly easy to combine molecular biology and synthetic organic chemistry in order to enable expeditious access to series of natural products. This review outlines the various ways of combining biology and chemistry that have been applied to analogue generation, drawing upon a series of examples to illustrate each approach.