Renal-clearable probes for disease detection and monitoring.

The demand for novel, minimally invasive, cost-effective, and easily readable diagnostic tools, primarily designed for the longitudinal monitoring of diseases and their treatments, has promoted the development of diagnostic systems that selectively target cells, tissues, or organs, at the same time minimizing their nonspecific accumulation, thus reducing the risk of toxicity and side effects. In this review, we explore the development of renal-clearable systems in non-invasive or minimally invasive detection protocols, all with the objective of minimizing nonspecific accumulation and its associated toxicity effects through quick renal excretion. These probes can identify molecules of interest or different healthy states of the patients through the direct analysis of urine (urinalysis).

Synthesis of a PdL Hydrazone Molecular Cage Through Multiple Reaction Pathways.

Molecular cages are preorganized molecules with a central cavity, typically formed through the reaction of their building blocks through chemical bonds. This requires, in most cases, forming and breaking reversible bonds during the cage formation reaction pathway for error correction to drive the reaction to the cage product. In this work, we focus on both Pd-ligand and hydrazone bonds implemented in the structure of a PdL hydrazone molecular cage.

CageCavityCalc (3): A Computational Tool for Calculating and Visualizing Cavities in Molecular Cages.

Organic(porous) and metal-organic cages are promising biomimetic platforms with diverse applications spanning recognition, sensing, and catalysis. The key to the emergence of these functions is the presence of well-defined inner cavities capable of binding a wide range of guest molecules and modulating their properties. However, despite the myriad cage architectures currently available, the rational design of structurally diverse and functional cages with specific host-guest properties remains challenging.

Comparing organic and metallo-organic hydrazone molecular cages as potential carriers for doxorubicin delivery.

Molecular cages are three-dimensional supramolecular structures that completely wrap guest molecules by encapsulation. We describe a rare comparative study between a metallo-organic cage and a fully organic analogous system, obtained by hydrazone bond formation self-assembly. Both cages are able to encapsulate the anticancer drug doxorubicin, with the organic cage forming a 1 : 1 inclusion complex with μM affinity, whereas the metallo-organic host experiences disassembly by interaction with the drug.

Water-Soluble Molecular Cages for Biological Applications.

The field of molecular cages has attracted increasing interest in relation to the development of biological applications, as evidenced by the remarkable examples published in recent years. Two key factors have contributed to this achievement: First, the remarkable and adjustable host-guest chemical properties of molecular cages make them highly suitable for biological applications. This allows encapsulating therapeutic molecules to improve their properties.

Chemical Strategies for the Detection and Elimination of Senescent Cells.

Cellular senescence can be defined as an irreversible stopping of cell proliferation that arises in response to various stress signals. Cellular senescence is involved in diverse physiological and pathological processes in different tissues, exerting effects on processes as differentiated as embryogenesis, tissue repair and remodeling, cancer, aging, and tissue fibrosis. In addition, the development of some pathologies, aging, cancer, and other age-related diseases has been related to senescent cell accumulation.

Picking the lock of coordination cage catalysis.

The design principles of metallo-organic assembly reactions have facilitated access to hundreds of coordination cages of varying size and shape. Many of these assemblies possess a well-defined cavity capable of hosting a guest, pictorially mimicking the action of a substrate binding to the active site of an enzyme. While there are now a growing collection of coordination cages that show highly proficient catalysis, exhibiting both excellent activity and efficient turnover, this number is still small compared to the vast library of metal-organic structures that are known.

Biosafety of mesoporous silica nanoparticles; towards clinical translation.

Mesoporous silica nanoparticles (MSNs) have attracted the attention of chemists, who have developed numerous systems for the encapsulation of a plethora of molecules, allowing the use of mesoporous silica nanoparticles for biomedical applications. MSNs have been extensively studied for their use in nanomedicine, in applications such as drug delivery, diagnosis, and bioimaging, demonstrating significant in vivo efficacy in different preclinical models. Nevertheless, for the transition of MSNs into clinical trials, it is imperative to understand the characteristics that make MSNs effective and safe.

Ficin-Cyclodextrin-Based Docking Nanoarchitectonics of Self-Propelled Nanomotors for Bacterial Biofilm Eradication.

Development of bioinspired nanomotors showing effective propulsion and cargo delivery capabilities has attracted much attention in the last few years due to their potential use in biomedical applications. However, implementation of this technology in realistic settings is still a barely explored field. Herein, we report the design and application of a multifunctional gated Janus platinum-mesoporous silica nanomotor constituted of a propelling element (platinum nanodendrites) and a drug-loaded nanocontainer (mesoporous silica nanoparticle) capped with ficin enzyme modified with β-cyclodextrins (β-CD).

Purely Covalent Molecular Cages and Containers for Guest Encapsulation.

Cage compounds offer unique binding pockets similar to enzyme-binding sites, which can be customized in terms of size, shape, and functional groups to point toward the cavity and many other parameters. Different synthetic strategies have been developed to create a toolkit of methods that allow preparing tailor-made organic cages for a number of distinct applications, such as gas separation, molecular recognition, molecular encapsulation, hosts for catalysis, etc. These examples show the versatility and high selectivity that can be achieved using cages, which is impossible by employing other molecular systems.

Computational Modeling of Supramolecular Metallo-organic Cages-Challenges and Opportunities.

Self-assembled metallo-organic cages have emerged as promising biomimetic platforms that can encapsulate whole substrates akin to an enzyme active site. Extensive experimental work has enabled access to a variety of structures, with a few notable examples showing catalytic behavior. However, computational investigations of metallo-organic cages are scarce, not least due to the challenges associated with their modeling and the lack of accurate and efficient protocols to evaluate these systems.

Exploiting Supramolecular Interactions to Control Isomer Distributions in Reduced-Symmetry [PdL] Cages.

High-symmetry metallosupramolecular architectures (MSAs) have been exploited for a range of applications including molecular recognition, catalysis, and drug delivery. Recently, there have been increasing efforts to enhance those applications by generating reduced-symmetry MSAs. Here we report our attempts to use supramolecular (dispersion and hydrogen-bonding) forces and solvophobic effects to generate isomerically pure [Pd(L)] cage architectures from a family of new reduced-symmetry ditopic tripyridyl ligands.

Rational Design of Simple Organocatalysts for the HSiCl Enantioselective Reduction of (E)--(1-Phenylethylidene)aniline.

Prolinamides are well-known organocatalysts for the HSiCl reduction of imines; however, custom design of catalysts is based on trial-and-error experiments. In this work, we have used a combination of computational calculations and experimental work, including kinetic analyses, to properly understand this process and to design optimized catalysts for the benchmark (E)--(1-phenylethylidene)aniline. The best results have been obtained with the amide derived from 4-methoxyaniline and the -pivaloyl protected proline, for which the catalyzed process is almost 600 times faster than the uncatalyzed one.

Damming an electronic energy reservoir: ion-regulated electronic energy shuttling in a [2]rotaxane.

We demonstrate the first example of bidirectional reversible electronic energy transfer (REET) between the mechanically bonded components of a rotaxane. Our prototypical system was designed such that photoexcitation of a chromophore in the axle results in temporary storage of electronic energy in a quasi-isoenergetic "reservoir" chromophore in the macrocycle. Over time, the emissive state of the axle is repopulated from this reservoir, resulting in long-lived, delayed luminescence.

Five-component, one-pot synthesis of an electroactive rotaxane comprising a bisferrocene macrocycle.

The templated clipping of a ferrocene-grafted isophthalic acid derivative to encircle a hydrogen-bonding axle through the reaction with 1,4-bis(aminomethyl)benzene is described. The constituent electroactive macrocycle of the resultant [2]rotaxane is a homologue of the versatile benchmark tetraamide variant developed by Leigh and co-workers. The relative templating effect of different hydrogen-bonding motifs in rotaxane and pseudorotaxane generation is compared, with yields varying from 0 to 41%.

Non-covalent allosteric regulation of capsule catalysis.

Allosteric regulation is an essential biological process that allows enzymes to modulate their active site properties by binding a control molecule at the protein exterior. Here we show the first example of capsule catalysis in which activity is changed by exotopic binding. This study utilizes a simple PdL capsule that can partition substrates and external effectors with high fidelity.

Rationalizing the Activity of an "Artificial Diels-Alderase": Establishing Efficient and Accurate Protocols for Calculating Supramolecular Catalysis.

Self-assembled cages have emerged as novel platforms to explore bioinspired catalysis. While many different size and shape supramolecular structures are now readily accessible, only a few are known to accelerate chemical reactions under substoichiometric conditions. These limited examples point to a poor understanding of cage catalysis in general, limiting the ability to design new systems.

Navigated Self-Assembly of a PdL Cage by Modulation of an Energy Landscape under Kinetic Control.

Kinetic control of molecular self-assembly remains difficult because of insufficient understanding of molecular self-assembly mechanisms. Here we report the formation of a metastable [PdL] cage structure composed of naphthalene-based ditopic ligands (L) and Pd(II) ions in very high yield (99%) under kinetic control by modulating the energy landscape. When self-assembly occurs with anionic guests in weakly cooordinating solvent then suitable intermedites and the metastable cage is formed.

High Activity and Efficient Turnover by a Simple, Self-Assembled "Artificial Diels-Alderase".

The Diels-Alder (DA) reaction is a cornerstone of synthesis, yet Nature does not use catalysts for intermolecular [4+2] cycloadditions. Attempts to create artificial "Diels-Alderases" have also met with limited success, plagued by product inhibition. Using a simple PdL capsule we now show DA catalysis that combines efficient turnover alongside enzyme-like hallmarks.

Quantitative Analysis of Self-Assembly Process of a Pd L Cage Consisting of Rigid Ditopic Ligands.

The self-assembly process of a Pd L cage complex consisting of rigid ditopic ligands, in which two 3-pyridyl groups are connected to a benzene ring through acetylene bonds and Pd ions was revealed by a recently developed quantitative analysis of self-assembly process (QASAP), with which the self-assembly process of coordination assemblies can be investigated by monitoring the evolution with time of the average composition of all the intermediates. QASAP revealed that the rate-determining steps of the cage formation are the intramolecular ligand exchanges in the final stage of the self-assembly: [Pd L Py* ] →[Pd L Py* ] +Py* and [Pd L Py* ] →[Pd L ] +Py* (Py*: 3-chloropyridine, which was used as a leaving ligand on the metal source). The energy barriers for the two reactions were determined to be 22.

Cu recognition by N,N'-benzylated bis(amino amides).

Two new C-symmetric N,N'-benzylated bis(amino amides) have been synthesised and their interaction with different transition metals studied using a variety of techniques including UV-Vis and CD spectroscopy or ESI-MS. The determination of the corresponding stability constants with Cu has been possible, in HO/CHCN 7/3 v/v, for one of these ligands (4) using potentiometric titrations. The results obtained reveal that N-benzylation affords significant changes to their properties and is accompanied by an appreciable decrease in the corresponding complexation stability constants.

Cu(2+), Zn(2+), and Ni(2+) Complexes of C2-Symmetric Pseudopeptides with an Aromatic Central Spacer.

Two new tetradentate C2-symmetric pseudopeptidic ligands derived from Val and Phe containing two amino and two amido groups and a central o-substituted aromatic spacer have been prepared. Their complexes with Cu(2+), Zn(2+), and Ni(2+) have been studied by potentiometry, UV-vis spectrophotometry, FT-IR, and ESI-MS. The presence of the aromatic spacer provides Cu(2+) complexes with stability constants several orders of magnitude higher than those observed for related ligands containing aliphatic central spacers.

Macrocycle Synthesis by Chloride-Templated Amide Bond Formation.

A new family of pseudopeptidic macrocyclic compounds has been prepared involving an anion-templated amide bond formation reaction at the macrocyclization step. Chloride anion was found to be the most efficient template in the macrocyclization process, producing improved macrocyclization yields with regard to the nontemplated reaction. The data suggest a kinetic effect of the chloride template, providing an appropriate folded conformation of the open-chain precursor and reducing the energy barrier for the formation of the macrocyclic product.

Nitrate Anion Recognition in Organic-Aqueous Solvent Mixtures by a Bis(triazolium)acridine-Containing [2]Rotaxane.

The synthesis of a novel [2]rotaxane host system containing a bis(triazolium)acridine-based axle component is reported. (1)H NMR anion-binding titrations reveal that the rotaxane is able to recognise selectively the NO3(-) anion over a range of more basic oxoanions (AcO(-), HCO3(-) and H2PO4(-)) in a competitive organic-aqueous solvent mixture.