Highly Rigid, Yet Conformationally Adaptable, Bisporphyrin -Cage Receptors Afford Outstanding Binding Affinities, Chelate Cooperativities, and Substrate Selectivities.

If we aim to develop efficient synthetic models of protein receptors and enzymes, we must understand the relationships of intra- and intermolecular interactions between hosts and guests and how they mutually influence their conformational energy landscape so as to adapt to each other to maximize binding energies and enhance substrate selectivities. Here, we introduce a novel design of cofacial (Zn)bisporphyrin cages based on dynamic imine bonding, which is synthetically simple, but at the same time highly robust and versatile, affording receptors composed of only -hybridized C and N atoms. The high structural rigidity of these cages renders them ideal hosts for ditopic molecules that can fit into the cavity and bind to both metal centers, leading to association constants as high as 10 M in chloroform.

Stacked or Folded? Impact of Chelate Cooperativity on the Self-Assembly Pathway to Helical Nanotubes from Dinucleobase Monomers.

Self-assembled nanotubes exhibit impressive biological functions that have always inspired supramolecular scientists in their efforts to develop strategies to build such structures from small molecules through a bottom-up approach. One of these strategies employs molecules endowed with self-recognizing motifs at the edges, which can undergo either cyclization-stacking or folding-polymerization processes that lead to tubular architectures. Which of these self-assembly pathways is ultimately selected by these molecules is, however, often difficult to predict and even to evaluate experimentally.

Enhanced Antitumoral Activity of Encapsulated BET Inhibitors When Combined with PARP Inhibitors for the Treatment of Triple-Negative Breast and Ovarian Cancers.

BRCA1/2 protein-deficient or mutated cancers comprise a group of aggressive malignancies. Although PARPis have shown considerably efficacy in their treatment, the widespread use of these agents in clinical practice is restricted by various factors, including the development of acquired resistance due to the presence of compensatory pathways. BETis can completely disrupt the HR pathway by repressing the expression of BRCA1 and could be aimed at generation combination regimes to overcome PARPi resistance and enhance PARPi efficacy.

Multifunctional PLA/Gelatin Bionanocomposites for Tailored Drug Delivery Systems.

A series of bionanocomposites composed of shark gelatin hydrogels and PLA nanoparticles featuring different nanostructures were designed to generate multifunctional drug delivery systems with tailored release rates required for personalized treatment approaches. The global conception of the systems was considered from the desired customization of the drug release while featuring the viscoelastic properties needed for their ease of storage and posterior local administration as well as their biocompatibility and cell growth capability for the successful administration at the biomolecular level. The hydrogel matrix offers the support to develop a direct thermal method to convert the typical kinetic trapped nanostructures afforded by the formulation method whilst avoiding the detrimental nanoparticle agglomeration that diminishes their therapeutic effect.

Self-Sorting Governed by Chelate Cooperativity.

Self-sorting phenomena are the basis of manifold relevant (bio)chemical processes where a set of molecules is able to interact with no interference from other sets and are ruled by a number of codes that are programmed in molecular structures. In this work, we study, the relevance of chelate cooperativity as a code for achieving high self-sorting fidelities. In particular, we establish qualitative and quantitative relationships between the cooperativity of a cyclic system and the self-sorting fidelity when combined with other molecules that share identical geometry and/or binding interactions.

A chiral interlocking auxiliary strategy for the synthesis of mechanically planar chiral rotaxanes.

Rotaxanes can display molecular chirality solely due to the mechanical bond between the axle and encircling macrocycle without the presence of covalent stereogenic units. However, the synthesis of such molecules remains challenging. We have discovered a combination of reaction partners that function as a chiral interlocking auxiliary to both orientate a macrocycle and, effectively, load it onto a new axle.

Dinucleoside-Based Macrocycles Displaying Unusually Large Chelate Cooperativities.

High-fidelity production of a single self-assembled species in competition with others relies on achieving strong chelate cooperativities, which can be quantified by the effective molarity parameter. Therefore, supramolecular systems displaying very high effective molarities are reliably formed in a wide range of experimental conditions and exhibit "all-or-none" phenomena, meaning that the assembly is either fully formed or fully dissociated into the corresponding monomeric components. We summarize here our efforts in the study and characterization of one of these synthetic systems exhibiting record chelate cooperativities: the self-assembly of rod-like dinucleoside molecules into tetrameric macrocycles through hydrogen-bonding Watson-Crick interactions.

Controlled Delivery of BET-PROTACs: In Vitro Evaluation of MZ1-Loaded Polymeric Antibody Conjugated Nanoparticles in Breast Cancer.

Bromo and extraterminal domain (BET) inhibitors-PROteolysis TArgeting Chimera (BETi-PROTAC) is a new family of compounds that induce proteasomal degradation through the ubiquitination of the tagged to BET inhibitors Bromodomain proteins, BRD2 and BRD. The encapsulation and controlled release of BET-PROTACs through their vectorization with antibodies, like trastuzumab, could facilitate their pharmacokinetic and efficacy profile. Antibody conjugated nanoparticles (ACNPs) using PROTACs have not been designed and evaluated.

An Overview of Antibody Conjugated Polymeric Nanoparticles for Breast Cancer Therapy.

Nanoparticles (NPs) are promising drug delivery systems (DDS) for identifying and treating cancer. Active targeting NPs can be generated by conjugation with ligands that bind overexpressed or mutant cell surface receptors on target cells that are poorly or not even expressed on normal cells. Receptor-mediated endocytosis of the NPs occurs and the drug is released inside the cell or in the surrounding tissue due to the bystander effect.

Antibody Conjugation of Nanoparticles as Therapeutics for Breast Cancer Treatment.

Breast cancer is the most common invasive tumor in women and the second leading cause of cancer-related death. Nanomedicine raises high expectations for millions of patients as it can provide better, more efficient, and affordable healthcare, and it has the potential to develop novel therapeutics for the treatment of solid tumors. In this regard, targeted therapies can be encapsulated into nanocarriers, and these nanovehicles are guided to the tumors through conjugation with antibodies-the so-called antibody-conjugated nanoparticles (ACNPs).

PEI-coated PLA nanoparticles to enhance the antimicrobial activity of carvacrol.

Carvacrol (CAR) is a natural bioactive compound with antioxidant and antimicrobial activity that is present in essential oils. The application of CAR in food preservation is hampered by its high volatility, low solubility in water, and susceptibility to light, heat and oxygen degradation. Polylactide (PLA) is an FDA-approved polymer derived from renewable resources.

Glucose Single-Chain Polymer Nanoparticles for Cellular Targeting.

Naturally occurring glycoconjugates possess carbohydrate moieties that fulfill essential roles in many biological functions. Through conjugation of carbohydrates to therapeutics or imaging agents, naturally occurring glycoconjugates are mimicked and efficient targeting or increased cellular uptake of glycoconjugated macromolecules is achieved. In this work, linear and cyclic glucose moieties were functionalized with methacrylates via enzymatic synthesis and used as building blocks for intramolecular cross-linked single-chain glycopolymer nanoparticles (glyco-SCNPs).

Stereoselective Synthesis of Mechanically Planar Chiral Rotaxanes.

Chiral interlocked molecules in which the mechanical bond provides the sole stereogenic unit are typically produced with no control over the mechanical stereochemistry. Here we report a stereoselective approach to mechanically planar chiral rotaxanes in up to 98:2 d.r.

Biocompatible Single-Chain Polymer Nanoparticles for Drug Delivery-A Dual Approach.

Single-chain polymer nanoparticles (SCNPs) are protein-inspired materials based on intramolecularly cross-linked polymer chains. We report here the development of SCNPs as uniquely sized nanocarriers that are capable of drug encapsulation independent of the polarity of the employed medium. Synthetic routes are presented for SCNP preparation in both organic and aqueous environments.

CO-Switchable Solvents as Entrainer in Fluid Separations.

CO-switchable solvents, typically neutral solvents that switch with CO into ionic species, were investigated for use as entrainer in fluid separations such as extractive distillation. Their switchable nature was investigated, which may facilitate liquid-liquid extraction or extractive distillation as ionic liquid (IL), whereas during regeneration their decarboxylation into the amine form prevents temperature shoot-up. Studied elements included a property screening and detailed mechanistic and kinetic studies on the switching of 2-ethylhexylamine and ,benzyl methylamine.

Positive and negative regulation of carbon nanotube catalysts through encapsulation within macrocycles.

One of the most attractive applications of carbon nanomaterials is as catalysts, due to their extreme surface-to-volume ratio. The substitution of C with heteroatoms (typically B and N as p- and n-dopants) has been explored to enhance their catalytic activity. Here we show that encapsulation within weakly doping macrocycles can be used to modify the catalytic properties of the nanotubes towards the reduction of nitroarenes, either enhancing it (n-doping) or slowing it down (p-doping).

Photoprogramming Allostery in Human Serum Albumin.

Developing strategies to interfere with allosteric interactions in proteins not only promises to deepen our understanding of vital cellular processes but also allows their regulation using external triggers. Light is particularly attractive as a trigger being spatiotemporally selective and compatible with the physiological environment. Here, we engineered a hybrid protein in which irradiation with light opens a new allosteric communication route that is not inherent to the natural system.

Photo-responsive Bioactive Surfaces Based on Cucurbit[8]uril-Mediated Host-Guest Interactions of Arylazopyrazoles.

A photoswitchable arylazopyrazole (AAP) derivative binds with cucurbit[8]uril (CB[8]) and methylviologen (MV ) to form a 1:1:1 heteroternary host-guest complex with a binding constant of K =2×10  m . The excellent photoswitching properties of AAP are preserved in the inclusion complex. Irradiation with light of a wavelength of 365 and 520 nm leads to quantitative E- to Z- isomerization and vice versa, respectively.

Illumination of Nanoliter-NMR Spectroscopy Chips for Real-Time Photochemical Reaction Monitoring.

We report the use of a small-volume nuclear-magnetic-resonance (NMR)-spectroscopy device with integrated fiber-optics for the real-time detection of UV-vis-light-assisted chemical reactions. An optical fiber is used to guide the light from LEDs or a laser diode positioned safely outside the magnet toward the 25 nL detection volume and placed right above the microfluidic channel, irradiating the transparent back of the NMR chip. The setup presented here overcomes the limitations of conventional NMR systems for in situ UV-vis illumination, with the microchannel permitting efficient light penetration even in highly concentrated solutions, requiring lower-power light intensities, and enabling high photon flux.

Understanding Noncovalent Interactions of Small Molecules with Carbon Nanotubes.

We combine experimental methods, density functional theory (DFT) calculations, and molecular dynamics (MD) simulations in the quantitative analysis of noncovalent interactions between (6,5)-enriched single-walled carbon nanotubes (SWNTs), as hosts, and a set of pyrene derivatives with different electronic properties and surface areas, as guests. The experiments and calculations were carried out in two solvents with markedly different polarities, namely 1,1',2,2'-tetrachloroethane (TCE) and N,N-dimethylformamide (DMF). Our results show that dispersion forces govern the supramolecular association of small molecules with (6,5)-SWNTs, with negligible contributions from ground-state charge-transfer effects.