Unique Building Block Research Articles

Repurposing the 3‐Isocyanobutanoic Acid Adenylation Enzyme SfaB for Versatile Amidation and Thioesterification

AbstractGenome mining of microbial natural products enables chemists not only to discover the bioactive molecules with novel skeletons, but also to identify the enzymes that catalyze diverse chemical reactions. Exploring the substrate promiscuity and catalytic mechanism of those biosynthetic enzymes facilitates the development of potential biocatalysts. SfaB is an acyl adenylate‐forming enzyme that adenylates a unique building block, 3‐isocyanobutanoic acid, in the biosynthetic pathway of the diisonitrile natural product SF2768 produced by Streptomyces thioluteus, and this AMP‐ligase was demonstrated to accept a broad range of short‐chain fatty acids (SCFAs). Herein, we repurpose SfaB to catalyze amidation or thioesterification between those SCFAs and various amine or thiol nucleophiles, thereby providing an alternative enzymatic approach to prepare the corresponding amides and thioesters in vitro.

A Water-Dispersible Quinoid-Resonant Conducting Polymer for Organic Electronics

Developing stable and solution-processable highly conductive polymers has been the research goal in organic electronics since the first demonstration of metallic conductive polyacetylene. Here, we used a unique quinoid-resonant building block thieno[3,4-b]thiophene (TbT) to develop a new water-dispersible conducting polymer, PTbT-Me:PSS. Linear polymerization and large surfactant counterion, poly(styrenesulfonate) (PSS−), were introduced, which enabled a high electrical conductivity of 68 S cm−1 and exhibited water-dispersible property. Interchain bipolaron was found in PTbT-Me:PSS when compared with polaron in PEDOT:PSS in their conducting mechanism. Moreover, we applied this highly conductive PTbT-Me:PSS as the solution-processed polymer thermoelectric material and a decent power factor of 3.1 μW m−1 K−2 was achieved.

Li4Ca2B8O16: A Borate with a Unique Fundamental Building Block and a Short Cutoff Edge.

A complex alkali and alkaline-earth metal borate Li4Ca2B8O16 has been synthesized successfully via the high-temperature solution method. Li4Ca2B8O16 crystallizes into the space group P1̅ (No. 2) of the triclinic crystal system. The crystal structure exhibits a three-dimensional framework consisting of the [B8O16]∞ chains connected by the [LiOn] (n = 3, 4, 6) and [CaO7] polyhedra. The fundamental building block [B8O18] differs from those of other anhydrous octa-borates, which can be identified as a unique one. Furthermore, Li4Ca2B8O16 shows three different Li-O units, which is unique among all non-disordered anhydrous borates. It shows a short UV cutoff edge less than 190 nm. To better study the relationships between the crystal structure and properties, the DFT calculations were used for the evaluations of the optical band gap and birefringence.

HFIP-Promoted de Novo Synthesis of Biologically Relevant Nonnatural α-Arylated Amino Esters and Dipeptide Mimetics.

Amino acids are fundamental building blocks, which have been extensively used in drug design and organic synthesis. However, nonnatural amino acids are relatively less studied. In this work, the authors report the first HFIP-promoted de novo synthesis of nonnatural α-arylated amino esters and dipeptide mimetics (27 examples, up to 99 % yield) from readily available amines, ethyl glyoxylate and electron-rich arenes under mild conditions, in which one C-C bond, one C-N bond and one chiral center were established simultaneously. The reaction was also performed on a gram scale, giving compound 4 a in 96 % yield. In addition, this protocol was successfully applied to the late-stage elaboration of drug molecules, such as tranylcypromine (TCP or PCPA) and troxipide. Interestingly, compound 4 h inactivated histone lysine specific demethylase 1 (LSD1) potently with an IC50 value of 0.296 μm. To the best of our knowledge, compound 4 h is the first LSD1 inhibitor derived from nonnatural α-arylated amino esters, and therefore could be used as a hit compound for the development of new LSD1 inhibitors. The synthesized nonnatural α-arylated amino esters and dipeptide mimetics as unique building blocks may have potential synthetic utilities.

Biosynthesis of Long Chain Base in Sphingolipids in animals, Plants and Fungi

Long chain base (LCB) is a unique building block found in sphingolipids. The initial step of LCB biosynthesis stems from serine:palmitoyl-CoA transferase enzyme, producing 3-ketodihydrosphingosine with multiple regulatory proteins including small subunit SPT a/b and orosomucoid-like protein1-3. 3-Ketodihydrosphingosine reductase and sphingolipid Δ4-desaturase, both of them poorly characterized mammalian enzymes, play key roles for neurological homeostasis based on their pathogenic mutation in humans. Ceramide synthase in mammals has six isoforms with distinct phenotype in each knockout mouse. In plants and fungi, sphingolipids also contain phytosphingosine due to sphingolipid C4-hydroxylase. In contrast to previous notion that dietary intake might be its major route in animals, emerging evidences suggested that phytosphingosine biosynthesis does occur in some tissues such as the skin by mammalian C4-hydroxylase activity of the DEGS2 gene. This short review summarizes LCB biosynthesis with their associating metabolic pathways in animals, plants and fungi.

Advancing Wireframe DNA Nanostructures Using Single-Molecule Fluorescence Microscopy Techniques.

DNA nanotechnology relies on the molecular recognition properties of DNA to produce complex architectures through self-assembly. The resulting DNA nanostructures allow scientists to organize functional materials at the nanoscale and have therefore found applications in many domains of materials science over the past several years. These scaffolds have been used to position proteins, nanoparticles, carbon nanotubes, and other nanomaterials with high spatial resolution. In addition to their remarkable performance as frameworks for other species, DNA constructs also possess interesting dynamic properties, which have led to their use in logic circuits, drug delivery vehicles, and molecular walkers. Although DNA nanostructures have become increasingly complex, the development of tools to study them has lagged. Currently, gel electrophoresis, dynamic light scattering, and ensemble fluorescence measurements are widely used to characterize DNA-based assemblies. Unfortunately, ensemble averaging in these methods obscures malformed structures and may mask properties associated with structure, length, and shape in polydisperse samples. While atomic force microscopy allows for the determination of morphology at the single-molecule level, this technique cannot typically be used to assess the dynamic properties of these constructs. To analyze the function of DNA-based devices such as molecular motors and reconfigurable nanostructures in real time, new single-molecule techniques are required. This Account details the work from our laboratories toward developing single-molecule fluorescence (SMF) methodologies for the structural and dynamic characterization of wireframe DNA nanostructures, one at a time. The methods described herein provide us with two separate yet related sets of information: First, we can statically examine the nanostructures one by one to assess their robustness, structural fidelity, and morphology. This is primarily done using two-color stepwise photobleaching, wherein we can examine the subunit stoichiometry of our assemblies before and after various perturbations to the structures. For example, we can introduce length mismatches to cause the nanotube to bend or perform strand displacement reactions to generate single-stranded, flexible analogues of our materials. Second, due to the unmatched spatiotemporal resolution of SMF techniques, we can study the dynamic character of these assemblies by implementing structural changes to the nanotube and monitoring them in real time. With this structural and dynamic information in hand, our groups have additionally developed new tools for the improved construction of DNA nanotubes, inspired by solid-phase DNA synthesis. By assembling the nanotubes in a stepwise manner, highly monodisperse nanostructures of any desired length can be made without a template strand. In this way, unique building blocks can also be added sequence-specifically, allowing for the production of user-defined scaffolds to organize nanoscale materials in three dimensions. This method, in combination with our imaging and analysis protocols, may be extended to assemble and inspect other supramolecular constructs in a controlled manner. Overall, by combining synthesis, characterization, and analysis, these single-molecule techniques hold the potential to advance the study of DNA nanostructures and dynamic DNA-based devices.

Associative intraligand substitution of anticancer azolato-bridged compounds without a square-pyramidal intermediate: Formation of a unique tetranuclear, µ3-1,2,3-triazolato-N1,N2,N3-bridged Pt(II) compound

The reaction of the anticancer azolato-bridged dinuclear platinum(II) compound [{cis-Pt(NH3)2}2(µ-OH)(µ-1,2,3-triazolato-N1,N2)](NO3)2 (AMTA) in 0.2 M DCl-D2O solution was monitored at 298 K using 1H NMR spectroscopy. Acid hydrolysis of AMTA first provided a dinuclear Pt(II) cationic species [{cis-Pt(NH3)2Cl}2(µ-1,2,3-triazolato-N1,N2)]+ (intermediate A) which then turned into [{cis-Pt(NH3)2Cl}2(µ-1,2,3-triazolato-N1,N3)]+ (intermediate B) by migration of a Pt(II) ion, initially bound to N2, to N3. Hence, intramolecular ligand substitution of N3 for N2 occurred after substitution of two chloride ligands for the hydroxido bridge. Under the reaction conditions, the intermediate A and B were unambiguously detected, and both or either of the intermediate species then dimerized by a substitution of the chlorido ligand by N3 or N2 of a partner molecule to yield an unprecedented tetranuclear Pt(II) compound [{cis-Pt(NH3)2Cl}µ-{cis-Pt(NH3)2}2(µ-1,2,3-triazolato-N2,N3)2-N1,N1′]Cl2(NO3)2 (compound 1), whose 3D structure has been determined by X-ray crystal analysis. The fact that all triazolate nitrogen atoms coordinated to 3 different Pt(II) ions indicates that 1,2,3-triazolate derivatives could be important as a unique tridentate building block for metal-organic framework.

Multi‐Component Self‐Assembly of Proteins and Inorganic Particles: From Discrete Structures to Biomimetic Materials

AbstractDue to their defined structure, proteins are suitable building blocks for the bottom‐up construction of multi‐component materials. Especially protein containers, with their inherent cavity, can be used to encapsulate synthetic components such as inorganic nanoparticles. This way, multi‐component discrete structures can be assembled. With recent advances in computational protein design, novel protein containers were successfully created, with a high potential for application in biomedicine and materials research. Moreover, engineered protein containers offer a unique building block for the self‐assembly of three‐dimensional materials. They combine the molecular precision of proteins with nanoscale dimensions. Designed interactions lead to novel protein scaffolds. In addition, nanoparticles encapsulated inside the container cavity introduce orthogonal functionality, important for the realization of nanostructured biomimetic materials with emergent properties.

Structural basis of the nonribosomal codes for nonproteinogenic amino acid selective adenylation enzymes in the biosynthesis of natural products.

Nonproteinogenic amino acids are the unique building blocks of nonribosomal peptides (NRPs) and hybrid nonribosomal peptide-polyketides (NRP-PKs) and contribute to their diversity of chemical structures and biological activities. In the biosynthesis of NRPs and NRP-PKs, adenylation enzymes select and activate an amino acid substrate as an aminoacyl adenylate, which reacts with the thiol of the holo form of the carrier protein to afford an aminoacyl thioester as the electrophile for the condensation reaction. Therefore, the substrate specificity of adenylation enzymes is a key determinant of the structure of NRPs and NRP-PKs. Here, we focus on nonproteinogenic amino acid selective adenylation enzymes, because understanding their unique selection mechanisms will lead to accurate functional predictions and protein engineering toward the rational biosynthesis of designed molecules containing amino acids. Based on recent progress in the structural analysis of adenylation enzymes, we discuss the nonribosomal codes of nonproteinogenic amino acid selective adenylation enzymes.

Ultrasound one pot synthesis of fused quinazolinones and quinazolinediones, screening and molecular docking study as phosphodiesterase 7A inhibitors.

Phosphodiesterase 7A enzyme is one the most recent targets for designing potent anti-inflammatory agents with minimal side effects. Quinazolinones are unique building blocks of wide biological activities. Different Quinazolinones were reported to act as Phosphodiesterase 7A inhibitors anti-inflammatory particularly against choronic inflammation and autoimmune disease. Ultrasound is a green convenient method for synthesis of different heterocyclic ring system that is advantageous in terms of yield and reaction time. Ultrasound was used for one pot synthesis of 3-substituted 6-aryl-dihydroisoindolo[2,1-a]quinazoline-5,11-diones and 3-Aryl quinazoline-2,4(1H,3H)-diones. Seventeen compounds were synthesized in good yields. The synthesized compounds were inspected for in vitro inhibitory activity against phosphodiesterase7A enzyme. Molecular docking was used to study the mode of interaction of all the synthesized compounds into the enzyme phosphodiesterase 7A binding site. Five compounds showed high inhibitory activity of enzyme Phosphodiesterase 7A at micro-molar level compared to reference drug. The compounds showed good recognition at the enzyme binding site in the molecular docking. There was a good agreement between the molecular docking and the biological screening results.

Electric field effects on the electronic structures of MoS2/antimonene van der Waals heterostructure

Van der Waals (vdW) heterostructure is attaching intensive attention as an unique building block in the construction of future nano-devices. In this work, the MoS2/antimonene vdW heterostructure has been investigated by the first-principles calculations, considering stacking patterns and external electric fields (Eext) effects. It is demonstrated that the MoS2/antimonene heterobilayers possess a type-II band alignment and an indirect band gap of 0.92 eV. Furthermore, the Eext can induce the semiconductor–metal transition of the MoS2/antimonene heterostructure. Interestingly, the band alignment transition from type-II to type-I can be also tuned using the strength and direction of Eext. Our study would open a new avenue for application of ultrathin MoS2/antimonene heterojunction in future nano- and optoelectronics.

Light-Driven Chiral Switching of Supramolecular Metallacycles with Photoreversibility

The construction of artificial chiral self-assembled systems has evolved to be one of the most attractive topics within supramolecular chemistry and materials science. However, stimuli-responsive chirality transcription with enantiospecific photoreversibility still remains challenging for chiral metallasupramolecular structures because of the lack of appropriate building blocks. Herein, we present a chiral photoresponsive family of diarylethene-containing dipyridyl donors and their coordination-driven self-assembly behavior with the 120° di-platinum(II) acceptor. The photochromic trimer units in the assembled metallacycles exhibit an unprecedented concerted photoconversion process without a step-by-step transformation. By taking advantage of the full-separated photoactive dipyridyl donor enantiomers based on the sterically hindered system, we have successfully achieved the phototriggered chirality transformation in supramolecular multi-dithienylethene metallacycles arising from axial helicity and central asymmetry, thereby establishing light-driven control in circular dichroism. Such unique photoreversible self-assembled metallacycles with photoinduced enantiospecificity enable the potential chemical platform for bistable chiroptical switching and non-destructive information encoding.Artificial chiral supramolecular architectures have been continuously aimed at mimicking natural biological macromolecules. However, light-driven chirality transcription with photoreversible enantiospecificity remains challenging. In this manuscript, we focus on a new family of light-driven chiral supramolecular metallacycles with a concerted, reversible, and enantiospecific transformation based on a unique chiral photoresponsive building block. As a delicate example of light-driven chiral supramolecular metallacycles with a reversible and enantiospecific transformation, we believe that the fundamental work presented herein is very guidable for developing light-driven supramolecular architectures, especially for stimuli-responsive chiral functional materials. The longer-term ambition is to establish a new platform for constructing chiral non-invasion photoswitching and extending their potential application in molecular information processing.An unprecedented light-driven chiral switching supramolecular system exhibits reversible and enantiospecific transformation along with a unique concerted photoconversion process. It is guidable for the development of light-driven supramolecular architectures, especially for stimuli-responsive chiral functional materials.

Understanding metal-enhanced fluorescence and structural properties in Au@Ag core-shell nanocubes.

Au@Ag core–shell structures have received particular interest due to their localized surface plasmon resonance properties and great potential as oxygen reduction reaction catalysts and building blocks for self-assembly. In this study, Au@Ag core–shell nanocubes (Au@AgNCs) were fabricated in a facile manner via stepwise Ag reduction on Au nanoparticles (AuNPs). The size of the Au@AgNCs and their optical properties can be simply modulated by changing the Ag shell thickness. Structural characterization has been carried out by TEM, SAED, and XRD. The metal-induced fluorescence properties of probe molecules near the Au@AgNCs were measured during sedimentation of the Au@AgNCs. The unique ring-like building block of Au@AgNCs has dual optical functions as a fluorescence quencher or fluorescence enhancement medium depending on the assembled regions.

Au7Ag9(dppf)3(CF3CO2)7BF4]n: a linear nanocluster polymer from molecular Au7Ag8 clusters covalently linked by silver atoms.

We report the total structure determination of a covalently bonded nanocluster polymer [Au7Ag9(dppf)3(CF3CO2)7BF4]n (1). This features a one-dimensional linear chain, consisting of unique molecular building blocks, Au7Ag8(dppf)3(CF3CO2)7 clusters, which are linked together by Ag-O bonds rather than Au-Au interactions or bidentate organic bridges as previously reported.

Nanoscale Crystalline Sheets and Vesicles Assembled from Nonplanar Cyclic π-Conjugated Molecules.

A fundamental challenge in chemistry and materials science is to create new carbon nanomaterials by assembling structurally unique carbon building blocks, such as nonplanar π-conjugated cyclic molecules. However, self-assembly of such cyclic π-molecules to form organized nanostructures has been rarely explored despite intensive studies on their chemical synthesis. Here we synthesized a family of new cycloparaphenylenes and found that these fully hydrophobic and nonplanar cyclic π-molecules could self-assemble into structurally distinct two-dimensional crystalline multilayer nanosheets. Moreover, these crystalline multilayer nanosheets could overcome inherent rigidity to curve into closed crystalline vesicles in solution. These supramolecular assemblies show that the cyclic molecular scaffolds are homogeneously arranged on the surface of nanosheets and vesicles with their molecular isotropic x-y plane standing obliquely on the surface. These supramolecular architectures that combined exact crystalline order, orientation-specific arrangement of π-conjugated cycles, controllable morphology, uniform molecular pore, superior florescence quench ability, and photoluminescence are expected to give rise to a new class of functional materials displaying unique photonic, electronic, and biological functions.

Phosphonium zwitterions for lighter and chemically-robust MOFs: highly reversible H2S capture and solvent-triggered release

The tetrahedral zwitterion of tetrakis(p-carboxyphenyl) phosphonium is employed as a unique building block for robust and lighter MOFs that tolerate sorption of acidic gases including H2S.

Hierarchical Cascading Algorithm for 2-D FEM Simulation of Finite SAW Devices.

Application of the finite-element method (FEM) for the simulation of surface acoustic wave (SAW) devices has been constrained by the large number of degrees of freedom required, resulting in large memory usage and long computation times. We propose a new 2-D algorithm that takes advantage of the periodic structure typical of SAW devices. The device is partitioned into small, repeatedly occurring building blocks. Only unique building blocks are simulated with FEM. The device geometry is presented as a hierarchical tree of cascading operations, where smaller blocks are combined into larger blocks. This is equivalent to the full FEM simulation of the device, implying the drastic reduction of memory consumption and simulation time for structures with a high degree of periodicity. The method is verified against FEM/BEM-based software. To ensure accurate and efficient simulation, the boundary conditions should be chosen according to the anisotropy of the substrate crystal.

Cover Feature: Synthesis of Functionalized Difluorocyclopropanes: Unique Building Blocks for Drug Discovery (Chem. Eur. J. 47/2018)

Cover Feature: Synthesis of Functionalized Difluorocyclopropanes: Unique Building Blocks for Drug Discovery (Chem. Eur. J. 47/2018)

Synthesis of Functionalized Difluorocyclopropanes: Unique Building Blocks for Drug Discovery.

Difluorocyclopropane-containing building blocks for drug discovery were synthesized from the functionalized alkenes and TMSCF3 /NaI. Novel fluorinated acids, amines, amino acids, alcohols, ketones and sulfonyl chlorides were obtained.

Highly Stable Spherical Metallo-Capsule from a Branched Hexapodal Terpyridine and Its Self-Assembled Berry-type Nanostructure.

Discrete spherical metallo-organic capsules at the nanometer scale, especially those constructed from unique building blocks, have received significant attention recently because of their fascinating molecular aesthetics and potential applications due to their compact cavities. Here, the synthesis and characterization of a hexapodal, branched terpyridine ligand are presented along with the nearly quantitative self-assembly of the resulting tetrameric metallo-nanosphere. This metallo-nanosphere exhibited four quasi-triangular and six rhombus-like facets, all of which were made by the same hook-like bis-terpyridine. Collision-induced dissociation experiments were done to investigate overall stability. The metallo-architecture and host-guest chemistry were investigated with coronene and fully characterized by 1D and 2D NMR, ESI-MS, and transmission electron microscopy. Furthermore, this metallo-nanosphere was observed to hierarchically self-assemble into berry-type structures in an acetonitrile/methanol mixture, by virtue of counterion-mediated attractions. The functional molecular metallo-nanosphere presented here expands the reach of terpyridine coordination systems into molecular containers and other model systems.