Molecular Building Blocks Research Articles

Reticular chemistry for the rational design of mechanically robust mesoporous merged-net metal-organic frameworks

Reticular chemistry for the rational design of mechanically robust mesoporous merged-net metal-organic frameworks

Single-Crystalline Hydrogen-Bonded Crosslinked Organic Frameworks and Their Dynamic Guest Sorption

ConspectusPorous organic framework materials constructed by periodically aligned molecular entities offer chemically tailored microenvironments to absorb molecules and ions for various applications. Fundamentally understanding the microenvironments of these porous organic materials─from pore size, shape, and dynamics to potential substrate binding sites─is critical for the rational design of porous organic materials. The solid-state structures of these porous organic materials, such as covalent organic frameworks (COFs), can provide unambiguous atomic-level structural details. However, it remains challenging to synthesize these materials as single crystals that can be fully characterized by single-crystal X-ray diffraction (SCXRD) or rotational electron diffraction (RED) analysis. In addition, the balance of single crystallinity, permanent porosity, and good chemical stability requires delicate control of the assembly of the molecular building blocks and covalent crosslinking during synthesis. In this Account, we discuss the development of hydrogen-bonded crosslinked organic frameworks (HCOFs) possessing balanced single crystallinity and high chemical stability. HCOFs are obtained through covalently crosslinking molecular crystals that are preorganized via hydrogen bonding. Due to the dual hydrogen-bonded network and covalent crosslinking, HCOFs can deform upon guest adsorption by breaking the hydrogen bonds and subsequently restore their original form through the desorption of guests by re-establishing the hydrogen-bonded networks. Thus, HCOFs can dynamically adjust their pore sizes according to the framework–substrate interactions. In the discussion, we link HCOFs with COFs and single-crystalline 2D polymers by comparing their synthetic approaches to accessing high crystallinity. The method to synthesize HCOFs allows for the employment of various flexible building blocks and linking motifs that are largely avoided in the current design regimes of COFs and 2D polymers. We also draw the connections between HCOFs and hydrogen-bonded organic frameworks (HOFs) by highlighting their shared design principles for constructing hydrogen-bonding networks with large voids. Compared to their hydrogen-bonded precursor crystals, reinforcing the hydrogen-bonded networks with covalent linkages endows HCOFs with enhanced chemical and structural stability. In addition, we emphasize that the structure elucidation of HCOFs often requires combined SCXRD analysis and experimental evidence, with the methods and challenges thoroughly discussed. The details are presented in the following sequence: (1) synthesizing single-crystalline COFs by matching the polycondensation rate to the nucleation rate and their subsequent analyses by SCXRD/RED; (2) obtaining single-crystalline polymers and networks through topochemical reactions; (3) constructing HOFs with designed voids using highly directional hydrogen bonding building blocks; and (4) developing HCOFs via monomer crystal engineering followed by single-crystal to single-crystal (SCSC) synthesis and studying their unique dynamic guest sorption behaviors. We hope this Account will inspire researchers to expand the synthetic methods for advancing HCOFs with detailed solid-state structures, as well as designing porous organic framework materials with dynamic sorption capabilities to enhance their performance for applications in molecular storage, separation, catalysis, etc.

(E)-2-styrylanthracene-9,10-dione derivatives as novel fluorescent probes: synthesis, photophysical properties and application in mitochondria imaging

Our previous work firstly reported that (E)-2-styrylanthracene-9,10-dione is a novel fluorescent core (EK01) with the ability of specific mitochondria imaging. In this effort, we mainly focused our attention on the structure-photophysical property relationship and application in cells imaging of this new fluorescent chemotype. A series of the structural derivatives (TZ series) were designed and synthesized by introducing some substituents onto the 2-styryl moiety. The structure-photophysical property relationship analysis suggested that TZ03 is an excellent fluorescent molecular building block with the property of fluorescent “turn-on” effect after the modification of acylation, and TZ07 is an excellent fluorescent dye with a series of advantages such as high fluorescence intensity (Fmax = 4049.0 in CH2Cl2, 25.80 μM), moderate molar extinction coefficients (3.77 × 103-5.93 × 103 mol−1∙L∙cm−1), strong fluorescence quantum yield (Φmax = 0.739 in CH2Cl2), large Stokes shift (99.0 nm-161.8 nm) and well biological tolerance. As a classical D-π-A structure, the ICT characteristic of TZ07 was analyzed through spectroscopy verification and DFT calculations. Furthermore, optimized compound TZ07 was successfully applied in the living cells imaging with the excellent selectivity to mitochondria in a green fluorescent form. It was also suggested that the mechanism of TZ07 targeting mitochondria is independent of mitochondrial membrane potential, but probably related to the mitochondrial complex I. These findings may provide some insights into the development of novel mitochondria-targeted fluorescent probes.

Molecular Shape and Polar Order in Columnar Liquid Crystals.

Bottom-up materials design by the conceiving of new molecular building blocks is powerful and chemists are uniquely qualified to innovate. Liquid crystals (LCs) and related soft crystals, collectively called mesophases, naturally create materials with dynamic properties. The thermotropic LC state has a liquid-like intermolecular disorder, but the cooperative nature of these materials facilitates a long-range directional order (alignment) that couples strongly to applied electric/magnetic fields and interfaces. Thermotropic LCs are held together by mesogen cores, which are often unsaturated with anisotropic polarizability, and are appended with flexible (often n-alkane) side chains. Thermal excitation of the side chains produces large amplitude motions that drive a melting transition, and the anisotropic attractions between mesogenic cores produce a directional organization that produces the LC order. LCs are liquids as defined by thermodynamics and may not contain three-dimensional (3D) organization. However, in many cases there are 3D ordered phases below the melting temperatures, which are soft (deformable) plastic materials. Unconventional mesogens offer opportunities to create responsive molecular assemblies with optical, electronic, or magnetic activity. I will detail in this account my efforts to control these dynamic states with the goal of creating polar organizations in columnar LCs. The use of molecular shape, dative bonding, and dynamic correlations between molecules in fluid/plastic phases will be highlighted and how applied electric fields can polarize select materials.

Chem-bio interface design for rapid conversion of CO2 to bioplastics in an integrated system

Chem-bio interface design for rapid conversion of CO2 to bioplastics in an integrated system

Braskem uses catalyst to breakdown waste plastics into molecular building blocks

Braskem uses catalyst to breakdown waste plastics into molecular building blocks

Marine phosphate availability and the chemical origins of life on Earth

Prebiotic systems chemistry suggests that high phosphate concentrations were necessary to synthesise molecular building blocks and sustain primitive cellular systems. However, current understanding of mineral solubility predicts negligible phosphate concentrations for most natural waters, yet the role of Fe2+, ubiquitous on early Earth, is poorly quantified. Here we determine the solubility of Fe(II)-phosphate in synthetic seawater as a function of pH and ionic strength, integrate these observations into a thermodynamic model that predicts phosphate concentrations across a range of aquatic conditions, and validate these predictions against modern anoxic sediment pore waters. Experiments and models show that Fe2+ significantly increases the solubility of all phosphate minerals in anoxic systems, suggesting that Hadean and Archean seawater featured phosphate concentrations ~103–104 times higher than currently estimated. This suggests that seawater readily met the phosphorus requirements of emergent cellular systems and early microbial life, perhaps fueling primary production during the advent of oxygenic photosynthesis.

Encoding Supramolecular Chiral Self‐Assembly with Photo‐Controlled Circularly Polarized Luminescence by Overcrowded Alkene‐Based Bis‐PBI Modulators

AbstractDeveloping photoresponsive circularly polarized luminescence (CPL) materials is an essential step for biosensing and biomedical applications. However, fabricating CPL assemblies rooted in the chirality amplification and transmission of the molecular building blocks, which simultaneously show photo‐controllable CPL signals, remains challenging. Herein, a molecular building block containing an overcrowded‐alkene core and bis‐PBI (MPBI) was designed. Importantly, the enantiopure MPBI can self‐assemble into well‐organized nanofibers via π‐π stacking interactions and enable the transmission of the intrinsic chirality, providing opposite CPL signals. The photoisomerization of MPBI induced a transformation from nanofibers to discrete nanospheres, accompanied by a gradually decreased CPL signal. The results demonstrated the development of photo‐controllable CPL materials from the assembly of chiral MPBI, which provides an alternatively facile strategy to fabricate CPL‐active materials and would offer opportunities for future biosensing and biomedical applications.

Encoding Supramolecular Chiral Self-Assembly with Photo-Controlled Circularly Polarized Luminescence by Overcrowded Alkene-Based Bis-PBI Modulators.

Developing photoresponsive circularly polarized luminescence (CPL) materials is an essential step for biosensing and biomedical applications. However, fabricating CPL assemblies rooted in the chirality amplification and transmission of the molecular building blocks, which simultaneously show photo-controllable CPL signals, remains challenging. Herein, a molecular building block containing an overcrowded-alkene core and bis-PBI (MPBI) was designed. Importantly, the enantiopure MPBI can self-assemble into well-organized nanofibers via π-π stacking interactions and enable the transmission of the intrinsic chirality, providing opposite CPL signals. The photoisomerization of MPBI induced a transformation from nanofibers to discrete nanospheres, accompanied by a gradually decreased CPL signal. The results demonstrated the development of photo-controllable CPL materials from the assembly of chiral MPBI, which provides an alternatively facile strategy to fabricate CPL-active materials and would offer opportunities for future biosensing and biomedical applications.

Adsorption of apple xyloglucan on cellulose nanofiber depends on molecular weight, concentration and building blocks

Apple xyloglucan (XyG) structural features (molecular weight and building motifs) were studied in relation with the hemicellulose interaction with cellulose nanofiber (CNF) through adsorption isotherm, high performance size exclusion chromatography and high-performance anion exchange chromatography analyses. Up to 75.6 μg of apple XyG adsorbed/mg of CNF. XyG adsorption depended on both Mw and XyG/CNF ratio. The adsorption capacity increased with Mw irrespectively of XyG/CNF ratio. At XyG/CNF ratio > 0.05, the adsorption of high Mw populations (2.0 × 105, 7.9 × 104 g mol−1) gradually ceased, while it kept increasing for low Mw populations (2.6 × 104, 1.2 × 104 g mol−1). The unbranched glucan segments and the galactosylated XLLG motif showed the highest binding affinity to CNF. Most of the XLLG motif was found in “loops and tails”, whereas most of the XyG unbranched glucan segments interact directly with CNF.

Synthetic cannabinoids and their semi-systematic naming developed in Europe – Overview of the chemical diversity and practical guidelines

A nomenclature for the naming of synthetic cannabinoids (SC) notified to the EMCDDA was developed. The harmonized names shall convey the structural features of SCs accurately and consistently without the need for a complex systematic name. SCs are the largest group of new psychoactive substances monitored by the EMCDDA and are heterogeneous in their structural makeup. Consistent, concise, and informative naming of SCs has been an ongoing challenge. Over time, several naming conventions have been employed to refer to SCs to avoid the complex but unambiguous systematic IUPAC name, which gives clear hints at the molecular features. Each naming approach aims to make SCs accessible to and recognizable by non-chemists/non-experts/regulators. However, ease of pronunciation and simplicity comes at the cost of detailed information on the structure accessible through the assigned name. All compounds classified as cannabinoids monitored by the EMCDDA were analyzed, and the four building blocks in each SC were identified and abbreviated using consistent letter codes. Inconsistencies in the formerly used names were reviewed and included in developing new consistent letter codes. Rules of the nomenclature and an expanded syntax that combines the letter codes abbreviating the structural features, were developed. The developed nomenclature enables the consistent naming of SCs, which is easy to understand and can be applied by the forensic community, researchers, clinical practitioners, and policy-makers alike. The framework is presented with hands-on guidelines and examples. The chemical diversity of SCs is visualized and made accessible through an electronic data file on all 227 SCs covered. The nomenclature was built on the established letter code system for the molecular building blocks (core, linker, linked group, and tail) implemented by the EMCDDA in 2011 and was expanded to incorporate more structural features through substitution. The main principle of the nomenclature is to reuse previously assigned letter codes, making it easier to recognize the molecular structures. The overall vocabulary is limited by sharing abbreviations of common features across building blocks. Whenever a letter code has to be derived for a new moiety, all previous building blocks and the derived letter codes are taken into account to maximize consistency and minimize complexity. The time of notification of an SC significantly impacts the letter code assigned to the molecular structure. Because of this, the scope of application for the nomenclature has intentionally been limited to SCs which have emerged on the drug market. The developed nomenclature streamlines the process of assigning letter codes to SCs. The nomenclature has already been used to assign names to the most recent SCs detected in the EU. The formerly used name (common name) will continue to be available for reference purposes.

All‐Small‐Molecule Dynamic Covalent Hydrogels with Heat‐Triggered Release Behavior for the Treatment of Bacterial Infections

AbstractAll‐small‐molecule smart hydrogels fabricated by naturally occurring and commercially available small molecular building blocks have attracted increasing interest due to their unique features such as biofunction integration and multi‐stimuli responsiveness. While a few examples have been well‐explored, the further development of additional kinds of all‐small‐molecule smart hydrogels is severely hindered by the lack of enough commensurate building blocks from nature and market. Therefore, it is crucial to seek new strategies to expand the scope of all‐small‐molecule dynamic covalent hydrogels using well‐established natural and commercial chemicals. Herein, this issue is addressed by introducing a bifunctional adapter bearing an aldehyde group and a boronic acid group to construct a novel all‐small‐molecule smart hydrogel through the dynamical covalent cross‐linking with naturally occurring building blocks (e.g., tobramycin and tannic acid). The prepared hydrogel presents several promising features including tunable mechanical property, multi‐stimuli responsiveness, controlled drug release profiles, and excellent in vitro and in vivo antibacterial performances. This study provides a new strategy to efficiently expand the scope of the all‐small‐molecule smart hydrogels via the integration of the naturally occurring building blocks and the bifunctional adapters.

Constitutionally Selective Dynamic Covalent Nanoparticle Assembly.

The future of materials chemistry will be defined by our ability to precisely arrange components that have considerably larger dimensions and more complex compositions than conventional molecular or macromolecular building blocks. However, exerting structural and constitutional control in the assembly of nanoscale entities presents a considerable challenge. Dynamic covalent nanoparticles are emerging as an attractive category of reaction-enabled solution-processable nanosized building block through which the rational principles of molecular synthetic chemistry can be extended into the nanoscale. From a mixture of two hydrazone-based dynamic covalent nanoparticles with complementary reactivity, specific molecular instructions trigger selective assembly of intimately mixed heteromaterial (Au–Pd) aggregates or materials highly enriched in either one of the two core materials. In much the same way as complementary reactivity is exploited in synthetic molecular chemistry, chemospecific nanoparticle-bound reactions dictate building block connectivity; meanwhile, kinetic regioselectivity on the nanoscale regulates the detailed composition of the materials produced. Selectivity, and hence aggregate composition, is sensitive to several system parameters. By characterizing the nanoparticle-bound reactions in isolation, kinetic models of the multiscale assembly network can be constructed. Despite ignoring heterogeneous physical processes such as aggregation and precipitation, these simple kinetic models successfully link the underlying molecular events with the nanoscale assembly outcome, guiding rational optimization to maximize selectivity for each of the three assembly pathways. With such predictive construction strategies, we can anticipate that reaction-enabled nanoparticles can become fully incorporated in the lexicon of synthetic chemistry, ultimately establishing a synthetic science that manipulates molecular and nanoscale components with equal proficiency.

Using sequence data to predict the self-assembly of supramolecular collagen structures

Collagen fibrils are the major constituents of the extracellular matrix, which provides structural support to vertebrate connective tissues. It is widely assumed that the superstructure of collagen fibrils is encoded in the primary sequences of the molecular building blocks. However, the interplay between large-scale architecture and small-scale molecular interactions makes the ab initio prediction of collagen structure challenging. Here, we propose a model that allows us to predict the periodic structure of collagen fibers and the axial offset between the molecules, purely on the basis of simple predictive rules for the interaction between amino acid residues. With our model, we identify the sequence-dependent collagen fiber geometries with the lowest free energy and validate the predicted geometries against the available experimental data. We propose a procedure for searching for optimal staggering distances. Finally, we build a classification algorithm and use it to scan 11 data sets of vertebrate fibrillar collagens, and predict the periodicity of the resulting assemblies. We analyzed the experimentally observed variance of the optimal stagger distances across species, and find that these distances, and the resulting fibrillar phenotypes, are evolutionary well preserved. Moreover, we observed that the energy minimum at the optimal stagger distance is broad in all cases, suggesting a further evolutionary adaptation designed to improve the assembly kinetics. Our periodicity predictions are not only in good agreement with the experimental data on collagen molecular staggering for all collagen types analyzed, but also for synthetic peptides. We argue that, with our model, it becomes possible to design tailor-made, periodic collagen structures, thereby enabling the design of novel biomimetic materials based on collagen-mimetic trimers.

Celda: a Bayesian model to perform co-clustering of genes into modules and cells into subpopulations using single-cell RNA-seq data.

Single-cell RNA-seq (scRNA-seq) has emerged as a powerful technique to quantify gene expression in individual cells and to elucidate the molecular and cellular building blocks of complex tissues. We developed a novel Bayesian hierarchical model called Cellular Latent Dirichlet Allocation (Celda) to perform co-clustering of genes into transcriptional modules and cells into subpopulations. Celda can quantify the probabilistic contribution of each gene to each module, each module to each cell population and each cell population to each sample. In a peripheral blood mononuclear cell dataset, Celda identified a subpopulation of proliferating T cells and a plasma cell which were missed by two other common single-cell workflows. Celda also identified transcriptional modules that could be used to characterize unique and shared biological programs across cell types. Finally, Celda outperformed other approaches for clustering genes into modules on simulated data. Celda presents a novel method for characterizing transcriptional programs and cellular heterogeneity in scRNA-seq data.

Vanillin: A Promising Biosourced Building Block for the Preparation of Various Heterocycles.

The preparation of heterocyclic compounds often involves the use of petroleum-based or non-renewable sources. Considering the actual societal and environmental awareness towards sustainable chemistry, new and green sources of organic carbon are sought. In this regard, vanillin is a molecular building block that can be obtained from the depolymerization of lignin. Due to its different functional groups (hydroxyl, aldehyde, and methoxy) vanillin can undergo a variety of reactions leading to various heterocycles such as pyrimidines, quinoxalines, imidazoles or thiazoles to name a few. This mini-review will focus on the preparation of accessible heterocycles building blocks from the vanillin moiety in regard to the medicinal, pharmaceutical, and material fields.

Dissipative discrete time crystals in a pump-modulated Kerr microcavity

Time crystals represent temporal analogues of the spatial self-ordering exhibited by atomic or molecular building blocks of solid-state crystals. The pursuit of discrete time crystals (DTCs) in periodically forced Floquet closed systems has revealed how they can evade thermalization and loss of temporal order. Recently, it has been shown that even with coupling to the ambient and its concomitant noise, some states maintain their time crystalline order, forming dissipative DTCs. Here, we introduce a scheme for the realization and state control of dissipative DTCs hinging on pumping a Kerr optical resonator with a phase-modulated continuous-wave laser. We show the possible symmetry breaking states possess temporal long-range order and analyze the phase noise of the accompanying signature radio frequency (RF) subharmonic. Besides offering a technique for generating high-spectral-purity RF signals, this versatile platform empowers controlled switching between various DTC states through accessible experimental knobs, hence facilitating the future study of DTC phase transitions.

Fluidized bed steam cracking of rapeseed oil: exploring the direct production of the molecular building blocks for the plastics industry

Fossil-based production of plastics represents a serious sustainability challenge. The use of renewable and biogenic resources as feedstocks in the plastic industry is imminent. Thermochemical conversion enables the production of the molecular building blocks of plastic materials from widely available biogenic resources. Waste cooking oil (WCO) represents a significant fraction of these resources. This work provides insights into the thermochemical conversion of the fatty acids present in WCO, where rapeseed oil is used as the source of fatty acids. The experimental results reveal that fluidized bed steam cracking of rapeseed oil in the temperature range of 650–750 °C yields a product distribution rich in light olefins and mono aromatics. Up to 51% of light olefins, 15% of mono aromatics, and 13% of light paraffins were recovered through steam cracking. This means that up to 70% of the carbon in rapeseed oil was converted into molecular building blocks in a single step. The main conclusion from this study is that WCO and vegetable oils represent viable biogenic feedstocks for the direct production of the molecular building blocks, where the conversion is achieved through steam cracking in fluidized beds.Graphical abstract

Nucleobase-Interaction-Directed Biomimetic Supramolecular Self-Assembly.

ConspectusThe design and fabrication of synthetic self-assembled systems that can mimic some biological features require exquisitely sophisticated components that make use of supramolecular interactions to attain enhanced structural and functional complexity. In nature, nucleobase interactions play a key role in biological functions in living organisms, including transcription and translation processes. Inspired by nature, scientists are progressively exploring nucleobase synthons to create a diverse range of functional systems with a plethora of nanostructures by virtue of molecular-recognition-directed assembly and flexible programmability of the base-pairing interactions. To that end, nucleobase-functionalized molecules and macromolecules are attracting great attention because of their versatile structures with smart and adaptive material properties such as stimuli responsiveness, interaction with external agents, and ability to repair structural defects. In this regard, a range of nucleobase-interaction-mediated hierarchical self-assembled systems have been developed to obtain biomimetic materials with unique properties. For example, a new “grafting to” strategy utilizing complementary nucleobase interactions has been demonstrated to temporarily control the functional group display on micellar surfaces. In a different approach, complementary nucleobase interactions have been explored to enable morphological transitions in functionalized diblock copolymer assembly. It has been demonstrated that complementary nucleobase interactions can drive the morphological transformation to produce highly anisotropic nanoparticles by controlling the assembly processes at multiple length scales. Furthermore, nucleobase-functionalized bottle brush polymers have been employed to generate stimuli-responsive hierarchical assembly. Finally, such interactions have been exploited to induce biomimetic segregation in polymer self-assembly, which has been employed as a template to synthesize polymers with narrow polydispersity. It is evident from these examples that the optimal design of molecular building blocks and precise positioning of the nucleobase functionality are essential for fabrication of complex supramolecular assemblies. While a considerable amount of research remains to be explored, our studies have demonstrated the potential of nucleobase-interaction-mediated supramolecular assembly to be a promising field of research enabling the development of biomimetic materials.This Account summarizes recent examples that employ nucleobase interactions to generate functional biomaterials by judicious design of the building blocks. We begin by discussing the molecular recognition properties of different nucleobases, followed by different strategies to employ nucleobase interactions in polymeric systems in order to achieve self-assembled nanomaterials with versatile properties. Moreover, some of their prospective biological/material applications such as enhanced drug encapsulation, superior adhesion, and fast self-healing properties facilitated by complementary nucleobase interactions are emphasized. Finally, we identify issues and challenges that are faced by this class of materials and propose future directions for the exploration of functional materials with the aim of promoting the development of nucleobase-functionalized systems to design the next generation of biomaterials.

Synthesis of Cyclic Fragrances via Transformations of Alkenes, Alkynes and Enynes: Strategies and Recent Progress.

With increasing demand for customized commodities and the greater insight and understanding of olfaction, the synthesis of fragrances with diverse structures and odor characters has become a core task. Recent progress in organic synthesis and catalysis enables the rapid construction of carbocycles and heterocycles from readily available unsaturated molecular building blocks, with increased selectivity, atom economy, sustainability and product diversity. In this review, synthetic methods for creating cyclic fragrances, including both natural and synthetic ones, will be discussed, with a focus on the key transformations of alkenes, alkynes, dienes and enynes. Several strategies will be discussed, including cycloaddition, catalytic cyclization, ring-closing metathesis, intramolecular addition, and rearrangement reactions. Representative examples and the featured olfactory investigations will be highlighted, along with some perspectives on future developments in this area.