Molecular Box Research Articles

Guidelines for Free-Energy Calculations Involving Charge Changes.

The Coulomb interactions in molecular simulations are inherently approximated due to the finite size of the molecular box sizes amenable to current-day compute power. Several methods exist for treating long-range electrostatic interactions, yet these approaches are subject to various finite-size-related artifacts. Lattice-sum methods are frequently used to approximate long-range interactions; however, these approaches also suffer from artifacts which become particularly pronounced for free-energy calculations that involve charge changes. The artifacts, however, also affect the sampling when plain simulations are performed, leading to a biased ensemble. Here, we investigate two previously described model systems to determine if artifacts continue to play a role when overall neutral boxes are considered, in the context of both free-energy calculations and sampling. We find that ensuring that no net-charge changes take place, while maintaining a neutral simulation box, may be sufficient provided that the simulation boxes are large enough. Addition of salt to the solution (when appropriate) can further alleviate the remaining artifacts in the sampling or the calculated free-energy differences. We provide practical guidelines to avoid finite-size artifacts.

The enhanced electrocatalytic performance of nanoscopic Cu6Pd12Fe12 heterometallic molecular box encaged cytochrome c.

Designing molecular cages for atomic/molecular scale guests is a special art used by material chemists to harvest the virtues of the otherwise vile idea known as "the cage". In recent years, there has been a notable surge in research investigations focused on the exploration and utilization of the distinct advantages offered by this art in the advancement of efficient and stable bio-electrocatalysts. This usually is achieved through encapsulation of biologically accessible redox proteins within specifically designed molecular cages and matrices. Herein, we present the first successful method for encaging cytochrome c (Cyt-c), a clinically significant enzyme system, inside coordination-driven self-assembled Cu6Pd12Fe12 heterometallic hexagonal molecular boxes (Cu-HMHMB), in order to create a Cyt-c@Cu-HMHMB composite. 1H NMR, FTIR, and UV-Vis spectroscopy, ICP-MS, TGA and voltammetric investigations carried out on the so-crafted Cyt-c@Cu-HMHMB bio-inorganic composite imply that the presented strategy ensures encaging of Cyt-c in a catalytically active, electrochemically stable and redox-accessible state inside the Cu-HMHMB. Cyt-c@Cu-HMHMB is demonstrated to exhibit excellent stability and electrocatalytic activity toward very selective, sensitive electrochemical sensing of nitrite exhibiting a limit of detection as low as 32 nanomolar and a sensitivity of 7.28 μA μM-1 cm-2. Importantly, Cyt-c@Cu-HMHMB is demonstrated to exhibit an excellent electrocatalytic performance toward the 4ē pathway oxygen reduction reaction (ORR) with an onset potential of 0.322 V (vs. RHE) and a Tafel slope of 266 mV dec-1. Our findings demonstrate that Cu-HMHMB is an excellent matrix for Cyt-c encapsulation. We anticipate that the entrapment-based technique described here will be applicable to other enzyme systems and Cyt-c for various electrochemical and other applications.

Anthracene-bridged “Texas-sized” box for the simultaneous detection and uptake of tryptophan

Tryptophan (Trp) is an essential amino acid that plays a critical role in human physiology. The increasing demand for Trp has created a highly promising market, underscoring the urgent necessity for the development of efficient strategies for the simultaneous detection and uptake of tryptophan. Herein, we report an expanded “Texas-sized” molecular box (An-TxSB), which incorporates luminescent anthracene bridging subunits and molecular recognition motifs. This luminescent molecular box demonstrates exceptional sensitivity to Trp in water, permitting its precise quantification with a notably low limit of detection (LOD) of 0.42 µmol/L. Moreover, An-TxSB facilitates the proficient uptake of Trp from simulated water samples, thereby revealing an impressive Trp adsorption capacity of up to 226.0 µmol/g.

Molecular dynamics of He encapsulation in the C20H20 cage at the threshold energy

The encapsulation of He inside C20H20 cage has been investigated in the framework of molecular dynamics for incident atom energy in a range close to the threshold value, corresponding to the projectile passing through the pentagonal carbon ring. The entrance of He atom into dodecahedrane is analyzed in terms of static and dynamic potential barriers. The details of helium capture inside the molecular box is revealed by using geometric and energetic parameters, being associated with the response of the atomic configuration near the collision site on the C20H20 cage. The energy transferred from the incident atom to deformation, vibrations, and recoil of the molecule target, was calculated as a function of the distance between the projectile and the collision site on C20H20 cage. The calculations show that the noble gas atom, encapsulated at the threshold of 315.62 Å/ps, oscillates across the void of the dodecahedrane with frequencies of 2.5, 22.5, and 25.0 THz, monitored for a time interval of 10 ps starting at helium penetration into C20H20. Molecular dynamics calculations are based on ab-initio Hartree-Fock method, considering an adiabatic process. This study reveals advantageous features of helium encapsulation in dodecahedrane molecules in designing super-molecular structures for advanced nano sensors in the field of THz detectors.

From isostructural to hetero-structural one-dimensional coordination polymers adjusted by changing the ligand substituent group from pyrazine to furan

A new ligand, 4-(4-carboxyphenyl)-6-(pyrazin-2-yl)picolinic acid (H2L1), was used to construct four isostructural one-dimensional (1 D) zig-zag chain coordination polymers ([M(L1)(H2O)2]·3H2O, M = Mn (1), Co (2), Cd (3) and Zn (4)). Moreover, when changing the ligand substituent group from pyrazine ring to furan ring, another new ligand, 4-(4-carboxyphenyl)-6-(furan-2-yl)picolinic acid (H2L2), was synthesized. Based on H2L2, different structural 1 D coordination polymers, ([Mn(L2)(H2O)2] (5) and [Ni(L2)(H2O)2]·H2O (6)), have been obtained under the same solvothermal conditions as for the syntheses of isostructural 1–4. Interestingly, only through changing the ligand substituent group, the 1 D isostructural zig-zag chain (1–4) was adjusted to a 1 D molecular box chain (5) and 1 D linear chain (6), which should be ascribed to ligand substituent group effects. The various 1 D chain structures originate from the types of ligand substituent group: the substituent group with a pyrazine ring only yields isostructural coordination polymers 1–4, whereas the substituent group with a furan ring can construct different structural coordination polymers, such as a 1 D molecular box chain (5) or a 1 D linear chain (6). The photoluminescent properties of all coordination polymers were also examined.

Structural diversities in the Zn(II), Mn(II) and Cd(II) coordination polymers induced by metal ions and/or anions

Under the same solvothermal conditions, nine novel coordination polymers (CPs), [Mn(L)(Cl)(H2O)] (1a), [Mn(L)(H2O)2]·(NO3) (2a), [MnL]·(HSO4)·MeCN·2H2O (3a), [Zn(L)2]·H2O (1b), [Zn(L)2] (2b and 3b), [Cd(L)]·Cl (1c), [Cd(L)(NO3)] (2c) and [CdL]·(HSO4)·2.5H2O (3c), were synthesized using a new ligand, namely 4-(2-chloroimidazo[1,2-a]pyridin-3-yl)-[2,4′-bipyridine]-6-carboxylic acid (HL). The Zn(II) CPs 1b-3b are similar 1D chains and their structures were mediated by the trigonal bipyramidal geometry of the Zn(II) cation, not by the counter-anions. However, when using Mn(II) and Cd(II) salts bearing various counter-anions (Cl−, NO3− or SO42−) as reagents, the Mn(II) (1a-3a) or Cd(II) (1c-3c) CPs do reveal different structures, which were induced by different anions acting as either a coordinated anion or a counter-anion for balancing the charge of 1a-3a or 1c-3c. When the larger NO3− anion replaced the Cl− anion, the 1D molecular box chain of 1a with a coordinated Cl− anion was changed to the 2D brickwall-type network of 2a with NO3− only as a counter-anion. However, the NO3− anion still could be coordinated to larger volume of the Cd(II) cation, leading to a 3D framework for 2c. Moreover, CPs 3a and 3c are isostructural, which could be induced by the much larger tetrahedral HSO4− counter-anion. Furthermore, the luminescent properties of the CPs have been investigated. The present work provides a promising approach to design and construct CPs or MOFs by adjusting metal salts bearing various counter-anions.

Tetradentate halogen bonding macrocyclic anion receptor inspired by the "Texas-sized" molecular box.

Inspired by the tetracationic "Texas-sized" molecular box, a neutral analogue containing four iodotriazole halogen bond-promoting subunits ("Ibox") was synthesized. This new macrocycle was prepared by means of azide-alkyne click chemistry. It was found to recognize Cl-, Br- and I- anions (as their tetrabutylammonium salts) in CDCl3. 1H NMR spectroscopic titrations revealed a higher affinity for the heavier halide anions and provided support for a preferred 1 : 2 binding stoichiometry.

Giant N-heterocyclic carbene-containing macrocycles for cobalt-catalysed hydroboration of alkynes.

Giant N-heterocyclic carbene-containing organic macrocycles larger than "Texas-sized" molecular boxes have been synthesized and structurally characterized. The new macrocycles were employed for the Co-NHC promoted syn-selective hydroboration of alkynes with good stereo- and regioselectivity.

Anion extractants constructed by macrocycle-based anion recognition

We summarize the recent approaches to macrocycle-based anion extraction, including those based on calix[4]pyrroles, and so-called “Texas-sized” molecular boxes.

Synergistic regulation of nonbinary molecular switches by protonation and light

We report a molecular switching ensemble whose states may be regulated in synergistic fashion by both protonation and photoirradiation. This allows hierarchical control in both a kinetic and thermodynamic sense. These pseudorotaxane-based molecular devices exploit the so-called Texas-sized molecular box (cyclo[2]-(2,6-di(1H-imidazol-1-yl)pyridine)[2](1,4-dimethylenebenzene); 14+, studied as its tetrakis-PF6- salt) as the wheel component. Anions of azobenzene-4,4'-dicarboxylic acid (2H+•2) or 4,4'-stilbenedicarboxylic acid (2H+•3) serve as the threading rod elements. The various forms of 2 and 3 (neutral, monoprotonated, and diprotonated) interact differently with 14+, as do the photoinduced cis or trans forms of these classic photoactive guests. The net result is a multimodal molecular switch that can be regulated in synergistic fashion through protonation/deprotonation and photoirradiation. The degree of guest protonation is the dominating control factor, with light acting as a secondary regulatory stimulus. The present dual input strategy provides a complement to more traditional orthogonal stimulus-based approaches to molecular switching and allows for the creation of nonbinary stimulus-responsive functional materials.

Pb2+-Containing Metal-Organic Rotaxane Frameworks (MORFs).

The metal-organic rotaxane framework (MORF) structures with the advantage of mechanically interlocking molecules (MIMs) have attracted intense interest from the chemical community. In this study, a set of MORFs (i.e., MORF-Pb-1 and MORF-Pb-2) are constructed using Pb2+, a tetraimidazolium macrocycle (Texas-sized molecular box; 14+), and aromatic dicarboxylate (p-phthalate dianions (PTADAs; 2) or 2,6-naphthalene dicarboxylate dianions (3)) via a one-pot three-layer diffusion protocol. In particular, an unusual Pb…Pb weak interaction was shown in MORF-Pb-1 (charactered with distance of 3.656 Å).

Using Slippage to Construct a Prototypical Molecular "Lock & Lock" Box.

We report a new slippage system based on p-tert-butylbenzyl-terminated imidazolium ions and di(ethylene glycol)-containing macrocycles and their use as linking units for the construction of a prototypical molecular "Lock & Lock" box from a resorcinarene-based cavitand "bowl" and a porphyrin "cover". The multivalent structure with four slippage linkers provided the molecular box with high stability, yet the system dissociated into its two components upon application of suitable external stimuli.

Chelation enforcing a dual gold configuration in the catalytic hydroxyphenoxylation of alkynes

AbstractThe functionalization of alkynes by Au (N‐heterocyclic carbene, NHC) complexes via the hydrophenoxylation reaction is a paradigm for the discussion between mono and dual metal catalysis. With the aim of mimicking the framework containing two gold units, achieved with molecular boxes, two NHC ligands were joined here with a chelated chain and this motif was examined in the hydrophenoxylation/hydroalkoxylation reactions through DFT calculations. This synthetic motif transforms the standard hydrophenoxylation intermolecular reaction from an inter‐ into an intra‐molecular nucleophilic attack, when forming the C–O bond. Various chain lengths were tested with regard to the coordination of the alkyne to the cationic NHC‐gold(I) center.

Targeting HMGB1 in the Treatment of Non-Small Cell Lung Adenocarcinoma

Evidence of immunogenic cell death as a predictor of response to cancer therapy has increased interest in the high molecular group box 1 protein (HMGB1). HMGB1 is a nuclear protein associated with chromatin organization and DNA damage repair. HMGB1 is also a damage-associated molecular pattern (DAMP) protein and promotes proinflammatory signaling in a paracrine and autocrine manner. Extracellular HMGB1 can promote activation of NF-kB and is associated with several chronic inflammatory and autoimmune diseases, including sepsis, rheumatoid arthritis, atherosclerosis, chronic kidney disease, systemic lupus erythematosus (SLE), as well as cancer. In this review, we describe studies that demonstrate the use of deacetylase inhibitors and HMGB1 inhibitors to alter the expression and localization of HMGB1 in cancer cells, with a focus on lung cancer. The drugs described herein are well established and frequently used in human and small mammal studies. The main objective of this review is to summarize the potential benefit of targeting posttranslational modification of HMGB1 to decrease inflammatory signaling in the tumor microenvironment, and perhaps lead to improved response to current immunotherapeutic approaches.

Porphyrin Based Porous Materials for Catalytic Application

Porous materials (PMs) such as metal–organic frameworks (MOFs), porous coordination polymers (PCPs), porous organic polymers (POPs), and polymers with intrinsic microporosity (PIMs), have received much attention due to their wide range of applications including catalysis, separation, gas storage, drug delivery, biosensing, and imaging. Although they have been successfully obtained by various synthetic techniques, their preparations are still a major task because the translation of building blocks into well-defined structures is challenging. In this regard, metalloporphyrins would be good building blocks for the construction of such functional materials witnessed by a wide range of molecular architectures using porphyrin derivatives, such as molecular boxes, self-assembled arrays, CPs and MOFs with various applications. In addition, they are often used to fabricate various architectures and to mimic the extraordinary performances of enzymes. Particularly, the heterogenization of homogeneous catalysts, such as immobilization and/or site-isolation of homogeneous catalysts using supporters are widely used strategies. In this regard, I like to present the preparations and heterogeneous catalytic uses of metalloporphyrins in various porous materials.References D. Y. Shin, J. H. Yoon, S. H. Kim, H. Baik, S. J. Lee,* "Immobilization of Porphyrinic Mn(III) Catalyst on a New Class of Silica Support Comprising Three-Dimensionally Interconnected Network with Two Different Sizes of Pores", Catal. Sci. Technol. 2018, 8, 6306-6310.J. Yi, H. Y. Jeong, D. Y. Shin, C. Kim, S. J. Lee,* "Mn(III)-Porphyrin Containing Heterogeneous Catalyst based on Microporous Polymeric Constituents as a New Class of Catalyst Support", ChemCatChem 2018, 10, 3974-3977.J. Yi, H. M. Ahn, J. H. Yoon, C. Kim, S. J. Lee,* " Preparation of a bispyridine based porous organic polymers as a new platform for Cu(II) catalyst and its use in heterogeneous olefin epoxidation", New J. Chem., 2018, 42, 14067-14070.

“Texas-Sized” Molecular Boxes: From Chemistry to Applications

The design and synthesis of novel macrocyclic host molecules continues to attract attention because such species play important roles in supramolecular chemistry. However, the discovery of new classes of macrocycles presents a considerable challenge due to the need to embody by design effective molecular recognition features, as well as ideally the development of synthetic routes that permit further functionalization. In 2010, we reported a new class of macrocyclic hosts: a set of tetracationic imidazolium macrocycles, which we termed “Texas-sized” molecular boxes (TxSBs) in homage to Stoddart’s classic “blue box” (CBPQT4+). Compared with the rigid blue box, the first generation TxSB displayed considerably greater conformational flexibility and a relatively large central cavity, making it a good host for a variety of electron-rich guests. In this review, we provide a comprehensive summary of TxSB chemistry, detailing our recent progress in the area of anion-responsive supramolecular self-assembly and applications of the underlying chemistry to water purification, information storage, and controlled drug release. Our objective is to provide not only a review of the fundamental findings, but also to outline future research directions where TxSBs and their constructs may have a role to play.

Naphthobox: a selective molecular box for planar aromatic cations

A molecular box with an electron-rich cavity, namely naphthobox, was contructed and showed selective binding to planar aromatic cations.

Preoperative sedentary behavior is neither a risk factor for perioperative neurocognitive disorders nor associated with an increase in peripheral inflammation, a prospective observational cohort study

BackgroundSurgical interventions result in a postoperative rise in circulating inflammatory cytokines and high molecular group box protein 1 (HMGB1). Herein, the impact of a sedentary lifestyle and other age-related factors on the development of perioperative neurocognitive disorders (PND) following non-cardiac surgical procedures was assessed in an older (55–75 years-old) surgical population.MethodsPrior to surgery, patients were asked questions regarding their sedentary behavior and daily habits. They also passed the Mini Mental State Examination (MMSE) and their blood circulating interleukin 6 (IL-6) and HMGB1 levels were assayed by ELISA. IL-6 and HMGB1 measurements were repeated respectively 6 and 24 h after surgery. MMSE was re-evaluated 6 weeks and whenever possible 3 months after surgery.ResultsThirty-eight patients were enrolled in the study from January until July 2019. The study identified self-sufficiency, multilinguism, and overall health score on the geriatric depression scale, as protectors against PND. No other demographic (age, sex), environmental (solitary/non-solitary housing, professional and physical activities, smoking, alcohol drinking), comorbidity (antipsychotic drug uptake, diabetic state) and type of surgery (orthopedic, general, genitourinary) influenced the development of PND. Although some factors (surgery type and age) influenced the surgery-induced rise in the circulating IL-6 levels, they did not impact HMGB1.ConclusionInflammaging, reflected by the greater increment of surgery-induced IL-6 in patients with advanced age, was present. As trauma-induced release of HMGB1 was not similarly affected by age, we surmise that HMGB1, rather than circulating cytokines, is the key driver of the trauma-induced inflammatory cascade leading to PND.Trial registrationClinicaltrials.gov identifier: NCT03805685.

Site Isolation of Catalytically Active Mn(III)-Porphyrin into Porous Materials

Porous materials (PMs) including porous coordination polymers (PCPs), metal–organic frameworks (MOFs), porous organic polymers (POPs), and polymers with intrinsic microporosity (PIMs), have received much attention and they often show novel and/or enhanced performances in wide range of applications such as catalysis, separation, gas storage, drug delivery, biosensing, and imaging. Although they can be successfully obtained by controlling the growth conditions, their fabrication is still a major challenge because of lack of information regarding the crucial factors for the precise control of particles during the synthesis. Furthermore, the translation of building blocks into well-defined structures, whose properties and functions are regulated in the building block level, still remains very challenging. In this regard, metalloporphyrins would be good building blocks for the construction of such functional materials witnessed by a wide range of molecular architectures, such as molecular boxes, self-assembled arrays, CPs and MOFs with various applications. Particularly, Mn(III)- and Fe(III)-containing metalloporphyrins are often used to fabricate various functional molecular architectures and to mimic the extraordinary behavior of enzymes in both homogeneous and heterogeneous catalytic systems.In the case of homogeneous catalysis, these materials have frequent trouble with fast catalytic degradation because of µ-oxo dimer formation or ligand oxidation. To avoid the catalyst degradation, the heterogenization of homogeneous catalysts, such as immobilization and/or site-isolation of homogeneous catalysts using supporters are widely used alternative strategies. In this regard, I like to present the preparations and heterogeneous catalytic uses of Mn(III)–porphyrin in various porous materials (PMs).

Shape, Size, and Internal Dynamics of Loosely Bound Colloidlike Ionic Clusters in Ternary Solvent Systems.

We characterize the influence of preferential solvation on the dynamic self-assembly process between small dianionic salts and a macrocyclic tetraimidazolium molecular box into highly defined, colloidlike ionic clusters in solution, called ionoids. Here, we substitute individual solvents in the established optimal ternary solvent mixture dimethyl sulfoxide (DMSO)/glycerol/water 50:43:7 (v/v/v), namely, DMSO through dimethyl formamide, glycerol through ethylene glycol and water through N-methylpropionamide, and such can characterize the changes in shape and size of the structures of loosely bound ionic clusters induced by the substitution of a specific solvent component. Using dynamic light scattering we associate size, shape, and initial durability of ionic clusters with solvent parameters like dynamic viscosity and relative permittivity to highlight the importance of solvent composition for the build-up of globular ionoids as well as anisotropic ionic clusters. To further analyze the solvation state of our dianionic building unit inside the initial ion cloud state, which later affects the self-assembly process of ionic clusters, we perform continuous wave (CW) electron paramagnetic resonance spectroscopy measurements at X-band (∼9.4 GHz) and Q-band (∼34 GHz) frequencies.