Convenient Building Block Research Articles

Straightforward Access to Chiral Phosphangulene Derivatives.

Polycyclic aromatic hydrocarbons including heteroatoms have found a wide range of applications, for instance, in supramolecular chemistry or material science. Phosphangulene derivatives are P-containing polycyclic aromatic hydrocarbons presenting a concave aromatic surface suitable for building supramolecular receptors. However, the applications of this convenient building block have been strongly hampered by a difficult and multistep preparation requiring several protection-deprotection sequences along with the use of harmful reagents. Here, we report a straightforward, protecting-group-free, three-step, and hundred-milligram-scale synthesis of a chiral phosphangulene oxide derivative via a triple phospho-Fries rearrangement. This compound was easily resolved by chiral HPLC and further functionalized, giving rise to versatile chiral phosphangulene derivatives. Following this strategy, chiral phosphangulene oxides with low symmetry were synthesized. Molecular crystal structures revealed a variety of molecular organization in the solid. This opens the way to wider use of this compound as a building block for cages or new materials.

Tetrazine-Derived Near-Infrared Dye for Targeted Photoacoustic Imaging of Bone.

A near-infrared photoacoustic probe was used to image bone in vivo through active and bioorthogonal pretargeting strategies that utilized coupling between a tetrazine-derived cyanine dye and a trans-cyclooctene-modified bisphosphonate. In vitro hydroxyapatite binding of the probe via active and pretargeting strategies showed comparable increases in percent binding vs a nontargeted control. Intrafemoral injection of the bisphosphonate-dye conjugate showed retention out to 24 h post-injection, with a 14-fold increase in signal over background, while the nontargeted dye exhibited negligible binding to bone and signal washout by 4 h post-injection. Intravenous injection, using both active and pretargeting strategies, demonstrated bone accumulation as earlier as 4 h post-injection, where the signal was found to be 3.6- and 1.5-fold higher, respectively, than the signal from the nontargeted dye. The described bone-targeted dye enabled in vivo photoacoustic imaging, while the synthetic strategy provides a convenient building block for developing new targeted photoacoustic probes.

Synthesis and reactivity of 9,10-bis(4-trimethylsilylethynylbuta-1,3-diynyl)anthracene derived chromophores.

9,10-Bis(4-trimethylsilylethynylbutadiynyl)anthracene is readily availabe from the reaction of anthraquinone and LiCCCCSiMe3 followed by reduction with Sn(II) and serves as a convenient building block via desilylation and palladium-mediated C-C coupling processes for the construction of further butadiynylanthracenes terminated by metal complexes, arenes, haloarenes and alkynyl functionalities.

An In Silico Methodology That Facilitates Decision Making in the Engineering of Nanoscale Protein Materials.

Under the need for new functional and biocompatible materials for biomedical applications, protein engineering allows the design of assemblable polypeptides, which, as convenient building blocks of supramolecular complexes, can be produced in recombinant cells by simple and scalable methodologies. However, the stability of such materials is often overlooked or disregarded, becoming a potential bottleneck in the development and viability of novel products. In this context, we propose a design strategy based on in silico tools to detect instability areas in protein materials and to facilitate the decision making in the rational mutagenesis aimed to increase their stability and solubility. As a case study, we demonstrate the potential of this methodology to improve the stability of a humanized scaffold protein (a domain of the human nidogen), with the ability to oligomerize into regular nanoparticles usable to deliver payload drugs to tumor cells. Several nidogen mutants suggested by the method showed important and measurable improvements in their structural stability while retaining the functionalities and production yields of the original protein. Then, we propose the procedure developed here as a cost-effective routine tool in the design and optimization of multimeric protein materials prior to any experimental testing.

Shape Symmetrization and IR-Spectral Enhancement of Aluminum Clusters via Doping with a Carbon Core.

Composite nanosystems are a class of objects with interesting and potentially useful properties. Here we study mixed-composition species representing interfaces at the molecular level between such technologically relevant materials as carbon and aluminum. Specifically, core-shell C8@Aln (n = 16, 18) species and their isomers with the core and relaxed-shell attached outside are investigated at a DFT level in terms of structures and stabilities, charge distributions and polarities, and IR spectra and electron affinities. Among the interesting findings is the possibility of bringing the aluminum cluster into a more symmetric shape (thus making a convenient building block) via insertion of a suitable molecular-carbon skeleton. Another notable feature is the system-selective dependence of polarity on spin multiplicity, suggesting possible molecular-electronic applications. The IR spectra of the composite species are much brighter compared to those of the separated components and are highly focused for the core-shell isomers. A related aspect of interest is the apparent reflections of the system structural details in the IR spectra features (line intensities and separations) via related vibrations, facilitating an experimental analysis of the structure and detection of the species formation and transformation as well as potentially enabling the means of achieving desirable optical characteristics via a geometric design.

Electric Field Modulated Peptide Nano-Assembly

Molecular self-assembly is an emerging and powerful tool in the synthesis of functional nanoscale structures as a bottom-up fabrication method. Among different self-assembling molecules, peptides are fascinating building blocks for the construction of supramolecular assemblies. The combination of facile chemical synthesis, flexibility in synthesis depending on the side-chain property, biocompatibility, and relative stability makes peptide a convenient building block for biological and bio-inspired self-assembly. Non-covalent interactions such as hydrophobic interaction, π- π stacking, van der Waals interaction and N and C terminal modifications have directed the self-assembly of peptides to supramolecular nanostructures. By mimicking the structures occurring in nature, peptide materials play a unique role in a new generation of hybrid materials. However, the challenge in this field is to control the self-assembly process in order to design a desirable structure at the nanometer scale in the correct orientation and configuration. Controlling the hierarchical organization of self-assembling peptides into nanostructures opens up the possibility of developing biocompatible functional nano materials for various applications. In this study, we focus on the fabrication of peptide nanomaterials formed by the self-assembly by employing electric field modulation. Self-assembly in the presence of external forces is an adaptive, directed organization of molecular components. While forces may be generated as a result of spontaneous interactions among components of a system, intervention with external forces can significantly alter the epitaxial growth of basic building blocks and stability of self-assembled architecture. Superimposing these intrinsic and extrinsic forces provide greater degrees of freedom to control the structure and function of self-assembling materials.

2,6-Dicyano-4-pyrone as a Novel and Multifarious Building Block for the Synthesis of 2,6-Bis(hetaryl)-4-pyrones and 2,6-Bis(hetaryl)-4-pyridinols

In this work, a three-stage and easily scalable synthesis of 2,6-dicyano-4-pyrone (overall yield of 45%) as a new convenient building block has been developed from diethyl acetonedioxalate. It was shown that the transformation with hydroxylamine and [3 + 2]-cycloaddition, in contrast to the reactions with hydrazines, selectively proceed through the attack at the cyano groups without the pyrone ring-opening to give symmetrical and unsymmetrical pyrone-bearing heterocyclic triads containing 1,2,4- and 1,3,4-oxadiazoles as well as tetrazole moieties. The reaction of 2,6-bis(hetaryl)-4-pyrones with ammonia afforded 2,6-bis(hetaryl)pyridines in 63–87% yields. The 4-pyridone/4-pyridinol tautomerism of 2,6-bis(hetaryl)pyridinols and the influence of the nature of adjacent azolyl moieties on this equilibrium have been discussed.

Solid-Phase-Supported Approach for the Preparation of Bioresponsive and Multifunctional MRI Probes.

The development of bifunctional imaging probes can often be challenging with difficult and time-consuming solution phase chemistry protocols and purification techniques. A solid phase synthetic protocol was therefore utilized to produce a functionalized derivative of a potent bismacrocyclic calcium-responsive contrast agent for magnetic resonance imaging. Through a convenient building block approach, the applicability of this methodology in the preparation and simple future development of multifunctional imaging probes was demonstrated.

Copper‐Catalyzed Annulation/A3‐Coupling Cascade: Diastereodivergent Synthesis of Sterically Hindered Monocyclic Oxazolidines Bearing Multiple Stereocenters

The Cu‐catalyzed synthesis of densely functionalized chiral oxazolidines with three stereogenic centers via an annulation/A3‐coupling cascade is described using chiral 1,2‐amino alcohol precursors. The solvent‐free synthetic approach tolerates an extremely broad substrate scope of the starting compounds (aldehydes, and alkynes), and provides the sterically hindered target monocyclic molecules with good yields and excellent diastereomeric ratio. Moreover, changing the alkyne to a propiolic acid is demonstrated here to be useful, and the corresponding titled products can be employed as a convenient building block for the preparation of 1,4‐diamino‐2‐butynes via one‐pot, two‐step sequential reaction.

Heterospirocyclic 3-Amino-2H-azirines as Convenient Building Blocks in Peptide Synthesis

Heterospirocyclic 3-amino-2H-azirines with a tetrahydropyran (Thp), tetrahydrothiopyran (Tht), or N-protected piperidine (Pip) moiety are useful reagents for the preparation of peptides containing the corresponding six-membered heterocyclic 4-amino-4-carboxylic acid unit. In the present study, tripeptides of the type H-Asp-D-Ala-Xaa-OMe, where Xaa is the heterocyclic amino acid, were prepared according to the ‘azirine/oxazolone method’.

Chiral Unsymmetrically Substituted Bipyridine N,N′‐Dioxides as Catalysts for the Allylation of Aldehydes

A series of unsymmetrically substituted diastereoisomeric (Ra,R) and (Sa,R) bipyridine N,N′‐dioxides was synthesized by using oxidative coupling of the corresponding metallated tetrahydroisoquinoline N‐oxides in the presence of iodine. The N,N′‐dioxides contained substituted aryl groups with electron‐donating or electron‐accepting groups in the near vicinity of the N,N′‐dioxide moiety. Their catalytic activity was tested in a series of reactions of allyltrichlorosilane with various substituted benzaldehydes, thiophenecarbaldehyde, and cinnamaldehyde. The reactions proceeded with high enantioselectivities (up to 98 % ee) with catalyst loadings as low as 0.5 mol‐%. Furthermore, allylation reactions of (E)‐3‐iodomethacrylaldehyde were also carried out to give chiral (E)‐1‐iodo‐2‐methylpenta‐1,4‐dien‐3‐ol, a convenient building block for the synthesis of natural products. The allylations proceeded with high enantioselectivities (up to ca. 99 % ee) with a catalyst loading of 2.5 mol‐%.

Dirac electron in a chiral space-time crystal created by counterpropagating circularly polarized plane electromagnetic waves

The family of solutions to the Dirac equation for an electron moving in an electromagnetic lattice with the chiral structure created by counterpropagating circularly polarized plane electromagnetic waves is obtained. At any nonzero quasimomentum, the dispersion equation has two solutions which specify bispinor wave functions describing electron states with different energies and mean values of momentum and spin operators. The inversion of the quasimomentum results in two other linearly independent solutions. These four basic wave functions are uniquely defined by eight complex scalar functions (structural functions), which serve as convenient building blocks of the relations describing the electron properties. These properties are illustrated in graphical form over a wide range of quasimomentums. The superpositions of two basic wave functions describing different spin states and corresponding to (i) the same quasimomentum (unidirectional electron states with the spin precession) and (ii) the two equal-in-magnitude but oppositely directed quasimomentums (bidirectional electron states) are also treated.

Synthesis and electrochemical investigation of beta-substituted thiophene-based donor–acceptor copolymers with 3,4-ethylenedioxythiophene (EDOT)

The present work reports the synthesis of four electron-acceptor beta-substituted thiophenes that were studied as monomers for electrochemical polymerization with 3,4-ethylenedioxythiophene (EDOT), an electron-donating monomer, aiming the combination of electron-acceptor and donor monomer thiophene to a simpler and convenient build up of novel donor–acceptor copolymeric materials via electrochemical polymerization. Four novel copolymers poly(EDOT-co-3-thiophene phenylacetate), (PEDOT-co-PPhTAc-2a), poly(EDOT-co-3-thiophene(4-nitrophenyl)acetate) (PEDOT-co-PPhTAc-2b), poly(EDOT-co-3-thiophenephenylcarboxylate) (PEDOT-co-PPhTCb), and poly(EDOT-co-3-(phenoxymethyl)thiophene) (PEDOT-co-PPhOMT) were electrochemically polymerized. The monomers were characterized by spectrometric techniques (FTIR, 1H NMR, and 13C NMR), and the copolymers were identified by electrochemical analyses and FT-IR. Although the corresponding homopolymers could not be obtained, in the presence of EDOT, the copolymers were formed in a quasi-reversible electrochemical kinetics. The infrared spectra of the copolymers as well the electrochemical profile corroborates their obtaining. The mass variation during the electrosynthesis was analyzed using a quartz crystal microbalance. The film’s morphologies were investigated by SEM. Interestingly, the combination of electron-rich monomer thiophene (EDOT) and these electron-deficient carboxy-substituted thiophenes might be a convenient building block couple to increase the performance control of physic-chemical properties of mixed polythiophenes with innovative applications and they also showed a possible applicability as charge storage device.

Development of Diubiquitin-Based FRET Probes To Quantify Ubiquitin Linkage Specificity of Deubiquitinating Enzymes.

Deubiquitinating enzymes (DUBs) are proteases that fulfill crucial roles in the ubiquitin (Ub) system, by deconjugation of Ub from its targets and disassembly of polyUb chains. The specificity of a DUB towards one of the polyUb chain linkages largely determines the ultimate signaling function. We present a novel set of diubiquitin FRET probes, comprising all seven isopeptide linkages, for the absolute quantification of chain cleavage specificity of DUBs by means of Michaelis–Menten kinetics. Each probe is equipped with a FRET pair consisting of Rhodamine110 and tetramethylrhodamine to allow the fully synthetic preparation of the probes by SPPS and NCL. Our synthetic strategy includes the introduction of N,N′‐Boc‐protected 5‐carboxyrhodamine as a convenient building block in peptide chemistry. We demonstrate the value of our probes by quantifying the linkage specificities of a panel of nine DUBs in a high‐throughput manner.

Bismuth(III)‐Promoted Acetylation of Thio­ethers into Thioacetates

AbstractThe thioacetate group is extensively employed as an anchoring group for attachment of molecules onto gold surfaces or between electrodes in molecular electronics. On account of its ready hydrolysis, it is often incorporated in the last step of a synthetic sequence from the corresponding tert‐butyl thioether. Here we present a particularly convenient method for this conversion using AcCl in combination with Bi(OTf)3, which is known as an environmentally friendly salt. A large variety of redox‐active and photoactive substrates with tert‐butyl thioether end‐cap(s) was prepared, including molecules incorporating dithiafulvene, dicyanoethylene, dihydroazulene, fulleropyrrolidine, and triazole units, and successfully subjected to a BiIII promoted conversion into products with thioacetate end‐cap(s). The azide group could also withstand these conditions, which allowed us to prepare S‐(4‐azidophenyl) ethanethioate that presents a convenient building block for subsequent CuAAC reactions.

A new P,S-coordinating ferrocenyl ligand: synthesis of a precursor and its coordination compounds with Pd(II) and Pt(II).

In our ongoing development of ferrocene ligands, 1-dimethylamino-2-(diphenylphosphinothioyl)ferrocene is being used as a convenient building block to obtain racemic or enantiomerically pure ligands. Using this building block in large excess allowed the formation of several by-products, two of which have already been reported; the structure of a third by-product, namely 1-(diphenylphosphinothioyl)-2-{[(diphenylphosphinothioyl)sulfanyl]methyl}ferrocene, [Fe(C5H5)(C30H25P2S3)], is presented here. The crystal structure is built up from a ferrocene unit, with one of the cyclopentadienyl (Cp) rings substituted in the 1- and 2-positions by a protected diphenylphosphinothioyl group and a [(diphenylphosphinothioyl)sulfanyl]methyl fragment, -CH2SP(=S)Ph2. There are C-H...S interactions which result in the formation of chains parallel to the c axis. After desulfurization, the crude material was then reacted with Pd and Pt (M) precursors [MCl2(CH3CN)2] to yield two isostructural dinuclear complexes arranged around twofold axes, namely (R,R/S,S)-bis{μ-[2-(diphenylphosphanyl)ferrocen-1-yl]methanethiolato-κ(3)P,S:S}bis[chloridopalladium(II)] pentane disolvate, [Pd2{Fe(C5H5)(C18H15PS)}2Cl2]·2C5H12, and the platinum(II) analogue, (R,R/S,S)-bis{μ-[2-(diphenylphosphanyl)ferrocen-1-yl]methanethiolato-κ(3)P,S:S}bis[chloridoplatinum(II)] toluene monosolvate, [Pt2{Fe(C5H5)(C18H15PS)}2Cl2]·C7H8, in which the two metal atoms present a slightly distorted square-planar geometry formed by two bridging S atoms and P and Cl atoms. The P,S-chelating ligand results from the rupture of one of the P-S bonds in the starting ligand. These dinuclear complexes display a butterfly geometry. Surprisingly, only the (R,R/S,S) diastereoisomer has been isolated.

Luminescence and electrical properties of single ZnO/MgO core/shell nanowires

To neutralise the influence of the surface of ZnO nanowires for photonics and optoelectronic applications, we have covered them with insulating MgO film and individually contacted them for electrical characterisation. We show that such a metal-insulator-semiconductor-type nanodevice exhibits a high diode ideality factor of 3.4 below 1 V. MgO shell passivates ZnO surface states and provides confining barriers to electrons and holes within the ZnO core, favouring excitonic ultraviolet radiative recombination, while suppressing defect-related luminescence in the visible and improving electrical conductivity. The results indicate the potential use of ZnO/MgO nanowires as a convenient building block for nano-optoelectronic devices.

Conversion of yeast mannan polysaccharide in mannose oligosaccharides with a thiopropargyl linker at the pseudo-reducing end

Polysaccharides are useful sources of preformed glycosyl linkages and therefore convenient building blocks can be prepared from them upon application of a proper degradation and derivatization scheme. Following this idea, the α-(1→6) linkages of this polysaccharide were broken applying acetolysis reaction and the pseudo-reducing position of the resulting acetylated mannose oligosaccharides was functionalized with a thiopropargyl appendage through thiourea activation of the related glycosyl iodides. Deacetylation of the final products and optimization of the purification procedures are discussed. The best yields were observed combining size exclusion chromatography and HPLC. Nine different oligosaccharides, from mono- to tetrasaccharides, mainly α-configured at the pseudo-reducing terminal, were obtained in pure form, presenting the propargyl appendage, a feature that makes them suitable substrates for successive functionalizations.

(4R,6R)-6-(hydroxymethyl)-4-methyltetrahydro-2H-pyran-2-one in the synthesis of polyfunctional compounds with the methyl-branched carbon skeleton

A simple and efficient asymmetrical synthesis was performed of a convenient bifunctional building block, methyl (R)-5,5-dimethoxy-3-methylpentanoate and its (S)-enantiomer. The possibility was shown of its application to the synthesis of insect pheromones.

Au(III)-Catalyzed Tandem Amination–Hydration of Alkynes: Synthesis of α-(N-2-Pyridonyl)ketones

A new Au(III)-catalyzed tandem amination-hydration reaction has been discovered, leading to the formation of α-(N-2-pyridonyl)ketones and heterocyclic analogues in good to excellent yields (14 examples, 48-90%). This reaction demonstrates the unusual use of a heterocyclic sp(2) nitrogen nucleophile in a gold-catalyzed 6-endo-dig cyclization. The tandem process allows rapid access to α-(N-2-pyridonyl)ketones, making them a convenient building block for the synthesis of more complex N-alkyl pyridone targets.