Effect of Polymorphism on the Sorption Properties of a Flexible Square-Lattice Topology Coordination Network.

The stimulus-responsive behavior of coordination networks (CNs), which switch between closed (nonporous) and open (porous) phases, is of interest because of its potential utility in gas storage and separation. Herein, we report two polymorphs of a new square-lattice (sql) topology CN, X-sql-1-Cu, of formula [Cu(Imibz)2]n (HImibz = {[4-(1H-imidazol-1-yl)phenylimino]methyl}benzoic acid), isolated from the as-synthesized CN X-sql-1-Cu-(MeOH)2·2MeOH, which subsequently transformed to a narrow pore solvate, X-sql-1-Cu-A·MeOH, upon mild activation (drying in air or heating at 333 K under nitrogen). X-sql-1-Cu-A·MeOH contains MeOH in cavities, which was removed through exposure to vacuum for 2 h, yielding the nonporous (closed) phase X-sql-1-Cu-A. In contrast, a more dense polymorph, X-sql-1-Cu-B, was obtained by exposing X-sql-1-Cu-(MeOH)2·2MeOH directly to vacuum for 2 h. Gas sorption studies conducted on X-sql-1-Cu-A and X-sql-1-Cu-B revealed different switching behaviors to two open phases (X-sql-1-Cu·CO2 and X-sql-1-Cu·C2H2), with different gate-opening threshold pressures for CO2 at 195 K and C2H2 at 278 K. Coincident CO2 sorption and in situ powder X-ray diffraction studies at 195 K revealed that X-sql-1-Cu-A transformed to X-sql-1-Cu-B after the first sorption cycle and that the CO2-induced switching transformation was thereafter reversible. The results presented herein provide insights into the relationship between two polymorphs of a CN and the effect of polymorphism upon gas sorption properties. To the best of our knowledge, whereas sql networks such as X-sql-1-Cu are widely studied in terms of their structural and sorption properties, this study represents only the second example of an in-depth study of the sorption properties of polymorphic sql networks.

Anticancer Potential of Dendritic Poly(aryl ether)-Substituted Polypyridyl Ligand-Based Ruthenium(II) Coordination Entities.

This paper studies the anticancer potency of dendritic poly(aryl ether)-substituted polypyridyl ligand-based ruthenium(II) coordination entities. The dendritic coordination entities were successfully designed, synthesized, and characterized by different spectral methods such as Fourier transform infrared (FTIR), 1H and 13C- NMR, and mass spectrometry. Further, to understand the structure and solvation behavior of the coordination entities, we performed all-atom molecular dynamics (MD) simulations. The behavior, configuration, and size of the coordination entities in DMSO and water were studied by calculating the radius of gyration (Rg) and solvent-accessible surface area (SASA). The MTT assay was used to assess the in vitro cytotoxicity of all of the coordination entities against cancerous A549 (lung cancer cells), MDA MB 231 (breast cancer cells), and HepG2 (liver cancer cells) and was found to be good with comparable IC50 values with respect to the standard drug cisplatin. The coordination entities exhibited dose dependence, and the highest activity was shown against HepG2 cell lines in comparison to the other cancer cell lines. In addition, fluorescence staining studies, such as AO/EB, DAPI, and cell death analysis by PI staining, were performed on the coordination entities to understand the apoptosis mechanism. Furthermore, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) assays confirmed apoptosis in cancer cells via the mitochondrial pathway. The DNA fragmentation assay was done followed by molecular docking analysis with DNA executed to strengthen and support the experimental observations.

Controlling self-assembling co-polymer coatings of hydrophilic polysaccharide substrates via co-polymer block length ratio.

HYPOTHESIS: The degree of polymerization of amphiphilic di-block co-polymers, which can be varied with ease in computer simulations, provides a means to control self-assembling di-block co-polymer coatings on hydrophilic substrates. SIMULATIONS: We examine self-assembly of linear amphiphilic di-block co-polymers on hydrophilic surface via dissipative particle dynamics simulations. The system models a glucose based polysaccharide surface on which random co-polymers of styrene and n-butyl acrylate, as the hydrophobic block, and starch, as the hydrophilic block, forms a film. Such setups are common in e.g. hygiene, pharmaceutical, and paper product applications. FINDINGS: Variation of the block length ratio (35 monomers in total) reveals that all examined compositions readily coat the substrate. However, strongly asymmetric block co-polymers with short hydrophobic segments are best in wetting the surface, whereas approximately symmetric composition leads to most stable films with highest internal order and well-defined internal stratification. At intermediate asymmetries, isolated hydrophobic domains form. We map the sensitivity and stability of the assembly response for a large variety of interaction parameters. The reported response persists for a wide polymer mixing interactions range, providing general means to tune surface coating films and their internal structure, including compartmentalization.

Single core and multicore aggregates from a polymer mixture: A dissipative particle dynamics study.

HYPOTHESIS: Multicore block copolymer aggregates correspond to self-assembly such that the polymer system spontaneously phase separates to multiple, droplet-like cores differing in the composition from the polymer surroundings. Such multiple core aggregates are highly useful capsules for different applications, e.g., drug transport, catalysis, controlled solvation, and chemical reactions platforms. We postulate that polymer system composition provides a direct means for designing polymer systems that self-assemble to such morphologies and controlling the assembly response. SIMULATIONS: Using dissipative particle dynamics (DPD) simulations, we examine the self-assembly of a mixture of highly and weakly solvophobic homopolymers and an amphiphilic block copolymer in the presence of solvent. We map the multicore vs single core (core-shell particles) assembly response and aggregate structure in terms of block copolymer concentration, polymer component ratios, and chain length of the weakly solvophobic homopolymer. FINDINGS: For fixed components and polymer chemistries, the amount of block copolymer is the key to controlling single core vs multicore aggregation. We find a polymer system dependent critical copolymer concentration for the multicore aggregation and that a minimum level of incompatibility between the solvent and the weakly solvophobic component is required for multicore assembly. We discuss the implications for polymer system design for multicore assemblies. In summary, the study presents guidelines to produce multicore aggregates and to tune the assembly from multicore aggregation to single core core-shell particles.

Copolyelectrolyte-Based Nanocapsules for Oral Monoclonal Antibody Therapy: A Mesoscale Modeling Survey.

Antibody therapy generally requires parenteral injection to attain the required bioavailability and pharmacokinetics, but improved formulations may slow enzymatic degradation of the antibody in the gastrointestinal tract, permitting the use of noninvasive oral delivery. Rationally designed carrier materials can potentially improve therapeutic activity both by shielding fragile biopharmaceuticals from proteolytic degradation and targeting specific receptors in vivo. One potentially useful class of protein carriers is block copolyelectrolytes, one polyelectrolyte plus one neutral hydrophilic polymer block, that self-assemble into stable micelles, providing a simple and biocompatible nanocapsule separating the protein from the outer medium. Here, we develop and implement an integrated mesoscale model to design molecular structures for block copolyelectrolyte nanocapsules predicted to protect Trastuzumab, an antibody used to treat breast cancer, in the low pH gastrointestinal tract and to selectively release this antibody in the more neutral intestinal environment. The simulations show a tightly packed self-assembled core-shell structure at pH = 3 that is ruptured and dynamically reassembled into a weaker structure at pH = 7. Our model identifies that the designed block copolyelectrolyte characteristics, such as block length ratio, can control the level of drug protection and release in vivo, providing simple design rules for engineering polyelectrolyte-based formulations that may allow oral administration of targeted antibody chemotherapies.

Modeling Polyzwitterion-Based Drug Delivery Platforms: A Perspective of the Current State-of-the-Art and Beyond.

Drug delivery platforms are anticipated to have biocompatible and bioinert surfaces. PEGylation of drug carriers is the most approved method since it improves water solubility and colloid stability and decreases the drug vehicles' interactions with blood components. Although this approach extends their biocompatibility, biorecognition mechanisms prevent them from biodistribution and thus efficient drug transfer. Recent studies have shown (poly)zwitterions to be alternatives for PEG with superior biocompatibility. (Poly)zwitterions are super hydrophilic, mainly stimuli-responsive, easy to functionalize and they display an extremely low protein adsorption and long biodistribution time. These unique characteristics make them already promising candidates as drug delivery carriers. Furthermore, since they have highly dense charged groups with opposite signs, (poly)zwitterions are intensely hydrated under physiological conditions. This exceptional hydration potential makes them ideal for the design of therapeutic vehicles with antifouling capability, i.e., preventing undesired sorption of biologics from the human body in the drug delivery vehicle. Therefore, (poly)zwitterionic materials have been broadly applied in stimuli-responsive "intelligent" drug delivery systems as well as tumor-targeting carriers because of their excellent biocompatibility, low cytotoxicity, insignificant immunogenicity, high stability, and long circulation time. To tailor (poly)zwitterionic drug vehicles, an interpretation of the structural and stimuli-responsive behavior of this type of polymer is essential. To this end, a direct study of molecular-level interactions, orientations, configurations, and physicochemical properties of (poly)zwitterions is required, which can be achieved via molecular modeling, which has become an influential tool for discovering new materials and understanding diverse material phenomena. As the essential bridge between science and engineering, molecular simulations enable the fundamental understanding of the encapsulation and release behavior of intelligent drug-loaded (poly)zwitterion nanoparticles and can help us to systematically design their next generations. When combined with experiments, modeling can make quantitative predictions. This perspective article aims to illustrate key recent developments in (poly)zwitterion-based drug delivery systems. We summarize how to use predictive multiscale molecular modeling techniques to successfully boost the development of intelligent multifunctional (poly)zwitterions-based systems.

Multicore Assemblies from Three-Component Linear Homo-Copolymer Systems: A Coarse-Grained Modeling Study.

Multicore polymer micelles and aggregates are assemblies that contain several cores. The dual-length-scale compartmentalized solvophobic-solvophilic molecular environment makes them useful for, e.g., advanced drug delivery, high-precision synthesis platforms, confined catalysis, and sensor device applications. However, designing and regulating polymer systems that self-assemble to such morphologies remains a challenge. Using dissipative particle dynamics (DPD) simulations, we demonstrate how simple, three-component linear polymer systems consisting of free solvophilic and solvophobic homopolymers, and di-block copolymers, can self-assemble in solution to form well-defined multicore assemblies. We examine the polymer property range over which multicore assemblies can be expected and how the assemblies can be tuned both in terms of their morphology and structure. For a fixed degree of polymerization, a certain level of hydrophobicity is required for the solvophobic component to lead to formation of multicore assemblies. Additionally, the transition from single-core to multicore requires a relatively high solvophobicity difference between the solvophilic and solvophobic polymer components. Furthermore, if the solvophilic polymer is replaced by a solvophobic species, well-defined multicore-multicompartment aggregates can be obtained. The findings provide guidelines for multicore assemblies' formation from simple three-component systems and how to control polymer particle morphology and structure.

Molecular Modelling Guided Modulation of Molecular Shape and Charge for Design of Smart Self-Assembled Polymeric Drug Transporters.

Nanomedicine employs molecular materials for prevention and treatment of disease. Recently, smart nanoparticle (NP)-based drug delivery systems were developed for the advanced transport of drug molecules. Rationally engineered organic and inorganic NP platforms hold the promise of improving drug targeting, solubility, prolonged circulation, and tissue penetration. However, despite great progress in the synthesis of NP building blocks, more interdisciplinary research is needed to understand their self-assembly and optimize their performance as smart nanocarriers. Multi-scale modeling and simulations provide a valuable ally to experiment by mapping the potential energy landscape of self-assembly, translocation, and delivery of smart drug-loaded NPs. Here, we highlight key recent advances to illustrate the concepts, methods, and applications of smart polymer-based NP drug delivery. We summarize the key design principles emerging for advanced multifunctional polymer topologies, illustrating how the unusual architecture and chemistry of dendritic polymers, self-assembling polyelectrolytes and cyclic polymers can provide exceptional drug delivery platforms. We provide a roadmap outlining the opportunities and challenges for the effective use of predictive multiscale molecular modeling techniques to accelerate the development of smart polymer-based drug delivery systems.

Effect of particle surface corrugation on colloidal interactions.

HYPOTHESIS: Production of corrugated particles generally introduces several morphological heterogeneities, such as surface roughness and local variations in the corrugation pattern, which are known from model system studies to significantly alter the colloidal interaction energy. Thus, realistic particle morphologies need to be investigated and compared to simple model shapes to yield insights into how interactions are influenced by such morphological heterogeneities. EXPERIMENTS: We applied the surface element integration method to study the colloidal interactions of electron tomography-based, realistic, corrugated colloidal particles and their symmetric, concave polyhedral analogs by differentiating local surface features to vertices, ridges and ridge networks. We applied molecular modelling to assess the surface access of these features. FINDINGS: Significant mixing of the interaction energy was found between the different surface features. Larger and smaller energy barrier heights and secondary minimum depths were observed compared to the concave polyhedral models with similar volume or surface area depending on the contacting surface feature. Analysis of surface area distributions suggests that the deviations originate from the altered effective contact distance as a result of surface roughness and other morphological heterogeneities. We also found that the surface access of nanoparticles is greatly impaired at the crevices between the surface corrugations.

A molecular simulation study on the adhesion behavior of a functionalized polyethylene-functionalized graphene interface.

Molecular dynamics simulations were applied to investigate interfacial adhesion between functionalized polyethylene (fPE) and functionalized graphene (fG) surfaces. In order to functionalize the PE and graphene surfaces, various types of functional groups were covalently bonded on the surfaces in a random manner. Adhesion between fPE and fG surfaces was evaluated by the calculation of work of separation (Wsep), while the interfaces were not allowed to relax. According to the simulation results, the combination of the atomic roughness effect and the electronic properties of the functional groups had influence on the adhesion between PE and graphene. The effect of surface reorganization was also investigated by devoting sufficient time for relaxation of the interface. The adhesion in the relaxed interfaces was evaluated via the work of adhesion (Wadh). Relaxation of the interface caused to decrease the atomic roughness of the PE surface, which enhanced adhesion in all of the systems compared to their unrelaxed models. In addition to surface flattening, relaxation also brought about an increase in the atomic density at the interface, which led to enhance the van der Waals interaction and increase interfacial adhesion.