Bioinspired Functional Catechol Derivatives through Simple Thiol Conjugate Addition.

The combination of the surface-adhesive properties of catechol rings and functional moieties conveying specific properties is very appealing to materials chemistry, but the preparation of catechol derivatives often requires elaborate synthetic routes to circumvent the intrinsic reactivity of the catechol ring. In this work, functional catechols are synthesized straightforwardly by using the bioinspired reaction of several functional thiols with o-benzoquinone. With one exception, the conjugated addition of the thiol takes place regioselectively at the 3-position of the quinone, and is rationalized by DFT calculations. Overall, this synthetic methodology provides a general and straightforward access to functional and chain-extended catechol derivatives, which are later tested with regard to their hydro-/oleophobicity, colloidal stability, fluorescence, and metal-coordinating capabilities in proof-of-concept applications.

Synthesis of Polydopamine-Like Nanocapsules via Removal of a Sacrificial Mesoporous Silica Template with Water.

Hollow polymeric polydopamine (PDA) micro-/nanocapsules have been obtained through a very simple, mild, and straightforward method that involves coating of silica mesoporous nanoparticles through an ammonia-triggered polymerization of PDA and the posterior removal of the sacrificial template simply by dispersion in water, without the need of any harsh chemical reagent, either in the presence or absence of active principles, from doxorubicin to iron oxide nanoparticles. To demonstrate the potential of the nanocapsules obtained with this new approach, they have been successfully used as nanocarriers for drug delivery.

Replacing Nitrogen by Sulfur: From Structurally Disordered Eumelanins to Regioregular Thiomelanin Polymers.

The oxidative polymerization of 5,6-dihydroxybenzothiophene (DHBT), the sulfur analog of the key eumelanin building block 5,6-dihydroxyindole (DHI), was investigated to probe the role of nitrogen in eumelanin build-up and properties. Unlike DHI, which gives a typical black insoluble eumelanin polymer on oxidation, DHBT is converted to a grayish amorphous solid (referred to as thiomelanin) with visible absorption and electron paramagnetic resonance properties different from those of DHI melanin. Mass spectrometry experiments revealed gradational mixtures of oligomers up to the decamer level. Quite unexpectedly, nuclear magnetic resonance (NMR) analysis of the early oligomer fractions indicated linear, 4-, and 7-linked structures in marked contrast with DHI, which gives highly complex mixtures of partially degraded oligomers. Density functional theory (DFT) calculations supported the tendency of DHBT to couple via the 4- and 7-positions. These results uncover the role of nitrogen as a major determinant of the structural diversity generated by the polymerization of DHI, and point to replacement by sulfur as a viable entry to regioregular eumelanin-type materials for potential applications for surface functionalization by dip coating.

Temperature-Controlled Switchable Photochromism in Solid Materials.

A novel strategy to achieve thermally switchable photochromism in solid materials is reported, which relies on the preparation of polymeric core-shell capsules containing solutions of photochromic dyes in acidic phase-change materials. Upon changing the phase (solid or liquid) of the encapsulated medium, one of the two photochromic states of the system is selectively stabilized on demand, allowing for reversible interconversion between direct and reverse photochromism when thermally scanning through the melting temperature of the phase-change material. This strategy, which does not require the addition of external agents or chemical modification of the dyes, proved to be general for different spiropyran photochromes and to be applicable to the fabrication of a variety of functional materials by simply embedding the capsules obtained into a solid matrix of choice.

Covalent Grafting of Coordination Polymers on Surfaces: The Case of Hybrid Valence Tautomeric Interphases.

We have developed a novel approach for grafting coordination polymers, structured as nanoparticles bearing surface reactive carboxylic groups, to amino-functionalized surfaces through a simple carbodiimide-mediated coupling reaction. As a proof-of-concept to validate our approach, and on the quest for novel hybrid interphases with potential technological applications, we have used valence tautomeric nanoparticles exhibiting spin transition at or around room temperature. SEM and AFM characterization reveal that the nanoparticles were organized chiefly into a single monolayer while X-ray photoelectron spectroscopy (XPS) measurements confirm that the nanoparticles retain a temperature-induced electronic redistribution upon surface anchorage. Our results represent an effective approach towards the challenging manufacture of coordination polymers.

Design and Synthesis of a Noninnocent Multitopic Catechol and Pyridine Mixed Ligand: Nanoscale Polymers and Valence Tautomerism.

The design and synthesis of a new redox-active ligand combining catechol and pyridine units have allowed the achievement of cobalt-based nanoscale coordination polymer particles in a single-step exhibiting a switchable valence tautomeric behavior and thermal hysteresis. The combination of polymerizing capabilities with redox-active responses in a unique ligand leads to the formation of nanoparticles exhibiting a gradual valence tautomeric interconversion in the 35-370 K temperature range. Using one single ligand to obtain these nanoparticles facilitates possible nanostructure formation methodologies.

Bioinspired catechol-terminated self-assembled monolayers with enhanced adhesion properties.

The role of the catechol moiety in the adhesive properties of mussel proteins and related synthetic materials has been extensively studied in the last years but still remains elusive. Here, a simplified model approach is presented based on a self-assembled monolayer (SAM) of upward-facing catechols thiol-bound to epitaxial gold substrates. The orientation of the catechol moieties is confirmed by spectroscopy, which also showed lack of significant amounts of interfering o-quinones. Local force-distance curves on the SAM measured by atomic force microscopy (AFM) shows an average adhesion force of 45 nN, stronger than that of a reference polydopamine coating, along with higher reproducibility and less statistical dispersion. This is attributed to the superior chemical and topographical homogeneity of the SAM coating. Catechol-terminated SAMs are also obtained on high-roughness gold substrates that show the ability to assemble magnetic nanoparticles, despite their lack of enhanced adhesion at the molecular level. Finally, the influence of the catechol group on the formation and quality of the SAM is explored both theoretically (molecular dynamics simulations) and experimentally using direct-write AFM lithography.

Carboxyl group (-CO2 H) functionalized coordination polymer nanoparticles as efficient platforms for drug delivery.

Functionalization of nanoparticles can significantly influence their properties and potential applications. Although researchers can now functionalize metal, metal oxide, and organic polymer nanoparticles with a high degree of precision, controlled surface functionalization of nanoscale coordination polymer particles (CPPs) has remained a significant challenge. The lack of methodology is perhaps one of the greatest roadblocks to the advancement of CPPs into high added-value drug delivery applications. Here, we report having achieved this goal through a stepwise formation and functionalization protocol. We fabricated robust nanoparticles with enhanced thermal and colloidal stabilities by incorporation of carboxyl groups and these surface carboxyl groups could be subsequently functionalized through well-known peptide coupling reactions. The set of chemistries that we employed as proof-of-concept enabled a plethora of new functional improvements for the application of CPPs as drug delivery carriers, including enhanced colloidal stabilities and the incorporation of additional functional groups such as polyethylene glycol (PEG) or fluorescent dyes that enabled tracking of their cellular uptake. Finally, we ascertained the cytotoxicity of the new CPP nanoparticles loaded with camptothecin to human breast adenocarcinoma (MCF-7). Efflux measurements show that the encapsulation of camptothecin enhances the potency of the drug 6.5-fold and increases the drug retention within the cell.

Controlling spin transition in one-dimensional coordination polymers through polymorphism.

A series of polymer 1 microcrystals with several different morphologies have been systematically synthesized by controlling experimental parameters, namely concentration of reactants, temperature, solvent nature, and the use of surfactants, and their valence tautomerism (VT) has been studied by combined electron microscopy, X-ray diffraction data, and magnetization. Our results indicate that all of them can be grouped exclusively into two different crystalline phases, or a mixture of them, that critically determine the VT process, independent of the morphology and/or dimensions of the crystals. Moreover, a difference in the critical temperature of both phases by more than 50 K allows us to regulate VT. These results head the use of valence tautomeric 1D polymers in devices where strict control and reproducibility of the switching behavior at different length scales and integration procedures is highly required.

Wearable, battery-free, wireless multiplexed printed sensors for heat stroke prevention with mussel-inspired bio-adhesive membranes.

Wearable technologies are becoming pervasive in our society, and their development continues to accelerate the untapped potential of continuous and ubiquitous sensing, coupled with big data analysis and interpretation, has only just begun to unfold. However, existing wearable devices are still bulky (mainly due to batteries and electronics) and have suboptimal skin contact. In this work, we propose a novel approach based on a sensor network produced through inkjet printing of nanofunctional inks onto a semipermeable substrate. This network enables real-time monitoring of critical physiological parameters, including temperature, humidity, and muscle contraction. Remarkably, our system operates under battery-free and wireless near-field communication (NFC) technology for data readout via smartphones. Moreover, two of the three sensors were integrated onto a naturally adhesive bioinspired membrane. This membrane, developed using an eco-friendly, high-throughput process, draws inspiration from the remarkable adhesive properties of mussel-inspired molecules. The resulting ultra-conformable membrane adheres effortlessly to the skin, ensuring reliable and continuous data collection. The urgency of effective monitoring systems cannot be overstated, especially in the context of rising heat stroke incidents attributed to climate change and high-risk occupations. Heat stroke manifests as elevated skin temperature, lack of sweating, and seizures. Swift intervention is crucial to prevent progression to coma or fatality. Therefore, our proposed system holds immense promise for the monitoring of these parameters on the field, benefiting both the general population and high-risk workers, such as firefighters.

Encapsulation and release mechanisms in coordination polymer nanoparticles.

The interplay of guest encapsulation and release mechanisms in nanoscale metal-organic vehicles and its effect on the drug-delivery kinetics of these materials were investigated through a new multidisciplinary approach. Two rationally-designed molecular guests were synthesized, which consist of a red-fluorescent benzophenoxazine dye covalently tethered to a coordinating catechol group and a protected, non-coordinating catechol moiety. This allowed loading of the guests into compositionally and structurally equivalent coordination polymer particles through distinct encapsulation mechanisms: coordination and mechanical entrapment. The two types of particles delivered their fluorescent cargo with remarkably different kinetic profiles, which could be satisfactorily modeled considering degradation- and diffusion-controlled release processes. This demonstrates that careful selection of the method of guest incorporation into coordination polymer nanoparticles allows selective tuning of the rate of drug delivery from these materials and, therefore, of the time window of action of the encapsulated therapeutic agents.

Water-Stable Upconverting Coordination Polymer Nanoparticles for Transparent Films and Anticounterfeiting Patterns with Air-Stable Upconversion.

Photon upconversion (UC) based on triplet-triplet annihilation is a very promising phenomenon with potential application in several areas, though, due to the intrinsic mechanism, the achievement of diffusion-limited solid materials with air-stable UC is still a challenge. Herein, we report UC coordination polymer nanoparticles (CPNs) combining sensitizer and emitter molecules especially designed with alkyl spacers that promote the amorphous character. Beyond the characteristic constraints of crystalline MOFs, amorphous CPNs facilitate high dye density and flexible ratio tunability. To show the universality of the approach, two types of UC-CPNs are reported, exhibiting highly photostable UC in two different visible spectral regions. Given their nanoscale, narrow size distribution, and good chemical/colloidal stability in water, the CPNs were also successfully printed as anticounterfeiting patterns and used to make highly transparent and photostable films for luminescent solar concentrators, both showing air-stable UC.

Platinum-Based Nanoformulations for Glioblastoma Treatment: The Resurgence of Platinum Drugs?

Current therapies for treating Glioblastoma (GB), and brain tumours in general, are inefficient and represent numerous challenges. In addition to surgical resection, chemotherapy and radiotherapy are presently used as standards of care. However, treated patients still face a dismal prognosis with a median survival below 15-18 months. Temozolomide (TMZ) is the main chemotherapeutic agent administered; however, intrinsic or acquired resistance to TMZ contributes to the limited efficacy of this drug. To circumvent the current drawbacks in GB treatment, a large number of classical and non-classical platinum complexes have been prepared and tested for anticancer activity, especially platinum (IV)-based prodrugs. Platinum complexes, used as alkylating agents in the anticancer chemotherapy of some malignancies, are though often associated with severe systemic toxicity (i.e., neurotoxicity), especially after long-term treatments. The objective of the current developments is to produce novel nanoformulations with improved lipophilicity and passive diffusion, promoting intracellular accumulation, while reducing toxicity and optimizing the concomitant treatment of chemo-/radiotherapy. Moreover, the blood-brain barrier (BBB) prevents the access of the drugs to the brain and accumulation in tumour cells, so it represents a key challenge for GB management. The development of novel nanomedicines with the ability to (i) encapsulate Pt-based drugs and pro-drugs, (ii) cross the BBB, and (iii) specifically target cancer cells represents a promising approach to increase the therapeutic effect of the anticancer drugs and reduce undesired side effects. In this review, a critical discussion is presented concerning different families of nanoparticles able to encapsulate platinum anticancer drugs and their application for GB treatment, emphasizing their potential for increasing the effectiveness of platinum-based drugs.

Design and synthesis of unnatural coordination glycopolymer particles (CGPs): unleashing the potential of catechol-saccharide derivatives.

Our study unveils an innovative methodology that merges catechols with mono- and disaccharides, yielding a diverse array of compounds. This strategic fusion achieves robust yields and introduces ligands with a dual nature: encompassing both the chelating attributes of catechols and the recognition capabilities of carbohydrates. This synergistic design led us to couple one of the novel ligands with an Fe(iii) salt, resulting in the creation of Coordination Glycopolymer Particles (CGPs). These CGPs demonstrate remarkable qualities, boasting outstanding dispersion in both aqueous media and Phosphate Buffered Saline (PBS) solution (pH ∼7.4) at higher concentrations (0.26 mg µL-1). Displaying an average Z-size of approximately 55 nm and favourable polydispersity indices (<0.25), these particles exhibit exceptional stability, maintaining their integrity over prolonged periods and temperature variations. Notably, they retain their superior dispersion and stability even when subjected to freezing or heating to 40 °C, making them exceptionally viable for driving biological assays. In contrast to established methods for synthesizing grafted glycopolymers, where typically a glycopolymer is doped with catechol derivatives to create synergy between chelating properties and those inherent to the saccharide, our approach provides a more efficient and versatile pathway for generating CGPs. This involves combining catechols and carbohydrates within a single molecule, enabling the fine-tuning of organic structure from a monomer design step and subsequently transferring these properties to the polymer.

Structuration and integration of magnetic nanoparticles on surfaces and devices.

Different experimental approaches used for structuration of magnetic nanoparticles on surfaces are reviewed. Nanoparticles tend to organize on surfaces through self-assembly mechanisms controlled by non-covalent interactions which are modulated by their shape, size and morphology as well as by other external parameters such as the nature of the solvent or the capping layer. Further control on the structuration can be achieved by the use of external magnetic fields or other structuring techniques, mainly lithographic or atomic force microscopy (AFM)-based techniques. Moreover, results can be improved by chemical functionalization or the use of biological templates. Chemical functionalization of the nanoparticles and/or the surface ensures a proper stability as well as control of the formation of a (sub)monolayer. On the other hand, the use of biological templates facilitates the structuration of several families of nanoparticles, which otherwise may be difficult to form, simply by establishing the experimental conditions required for the structuration of the organic capsule. All these experimental efforts are directed ultimately to the integration of magnetic nanoparticles in sensors which constitute the future generation of hybrid magnetic devices.

Switchable self-assembly of a bioinspired alkyl catechol at a solid/liquid interface: competitive interfacial, noncovalent, and solvent interactions.

The large tendency of catechol rings to adsorb on surfaces has been studied by STM experiments with molecular resolution combined with molecular-dynamics simulations. The strong adhesion is due to interactions with the surface and solvent effects. Moreover, the thermodynamic control over the differential adsorption of 1 and the nonanoic solvent molecules has been used to induce a new temperature-induced switchable interconversion. Two different phases that differ in their crystal packing and the presence of solvent molecules coexist upon an increase or decrease in the temperature. These results open new insight into the behavior of catechol molecules on surfaces and 2D molecular suprastructures.

Controlled positioning of nanoparticles on graphene by noninvasive AFM lithography.

Atomic force microscopy is shown to be an excellent lithographic technique to directly deposit nanoparticles on graphene by capillary transport without any previous functionalization of neither the nanoparticles nor the graphene surface while preserving its integrity and conductivity properties. Moreover this technique allows for (sub)micrometric control on the positioning thanks to a new three-step protocol that has been designed with this aim. With this methodology the exact target coordinates are registered by scanning the tip over the predetermined area previous to its coating with the ink and deposition. As a proof-of-concept, this strategy has successfully allowed the controlled deposition of few nanoparticles on 1 µm(2) preselected sites of a graphene surface with high accuracy.

Self-assembly of a catechol-based macrocycle at the liquid-solid interface: experiments and molecular dynamics simulations.

This combined experimental (STM, XPS) and molecular dynamics simulation study highlights the complex and subtle interplay of solvent effects and surface interactions on the 2-D self-assembly pattern of a Schiff-base macrocycle containing catechol moieties at the liquid-solid interface. STM imaging reveals a hexagonal ordering of the macrocycles at the n-tetradecane/Au(111) interface, compatible with a desorption of the lateral chains of the macrocycle. Interestingly, all the triangular-shaped macrocycles are oriented in the same direction, avoiding a close-packed structure. XPS experiments indicate the presence of a strong macrocycle-surface interaction. Also, MD simulations reveal substantial solvent effects. In particular, we find that co-adsorption of solvent molecules with the macrocycles induces desorption of lateral chains, and the solvent molecules act as spacers stabilizing the open self-assembly pattern.

Water-Stable Carborane-Based Eu3+/Tb3+ Metal-Organic Frameworks for Tunable Time-Dependent Emission Color and Their Application in Anticounterfeiting Bar-Coding.

Luminescent lanthanide metal-organic frameworks (Ln-MOFs) have been shown to exhibit relevant optical properties of interest for practical applications, though their implementation still remains a challenge. To be suitable for practical applications, Ln-MOFs must be not only water stable but also printable, easy to prepare, and produced in high yields. Herein, we design and synthesize a series of m CB-Eu y Tb 1-y (y = 0-1) MOFs using a highly hydrophobic ligand mCBL1: 1,7-di(4-carboxyphenyl)-1,7-dicarba-closo-dodecaborane. The new materials are stable in water and at high temperature. Tunable emission from green to red, energy transfer (ET) from Tb3+ to Eu3+, and time-dependent emission of the series of mixed-metal m CB-Eu y Tb 1-y MOFs are reported. An outstanding increase in the quantum yield (QY) of 239% of mCB-Eu (20.5%) in the mixed mCB-Eu0.1Tb0.9 (69.2%) is achieved, along with an increased and tunable lifetime luminescence (from about 0.5 to 10 000 µs), all of these promoted by a highly effective ET process. The observed time-dependent emission (and color), in addition to the high QY, provides a simple method for designing high-security anticounterfeiting materials. We report a convenient method to prepare mixed-metal Eu/Tb coordination polymers (CPs) that are printable from water inks for potential applications, among which anticounterfeiting and bar-coding have been selected as a proof-of-concept.

Intranasal Administration of Catechol-Based Pt(IV) Coordination Polymer Nanoparticles for Glioblastoma Therapy.

Cisplatin has been described as a potent anticancer agent for decades. However, in the case of glioblastomas, it is only considered a rescue treatment applied after the failure of second-line treatments. Herein, based on the versatility offered by coordination chemistry, we engineered nanoparticles by reaction of a platinum (IV) prodrug and iron metal ions showing in vitro dual pH- and redox-sensitivity, controlled release and comparable cytotoxicity to cisplatin against HeLa and GL261 cells. In vivo intranasal administration in orthotopic preclinical GL261 glioblastoma tumor-bearing mice demonstrated increased accumulation of platinum in tumors, leading in some cases to complete cure and prolonged survival of the tested cohort. This was corroborated by a magnetic resonance imaging follow-up, thus opening new opportunities for intranasal glioblastoma therapies while minimizing side effects. The findings derived from this research showed the potentiality of this approach as a novel therapy for glioblastoma treatment.