A crystalline sponge based on dispersive forces suitable for X-ray structure determination of included molecular guests

A crystalline porous material showing one-dimensional (1-D) rectangular micropores (12 × 9 Ų) has been assembled from a semirigid macrocyclic tetraimine and EtOAc as the templating agent. The 1-D nature of the material is intrinsic to the conformationally rigid structure of a macrocyclic sub-unit bearing four cyclohexylidene residues. The multiple dispersive forces established among the aliphatic residues glutted the 1-D channels and provided thermal stability to the material at temperatures below 160 °C. Upon removal of the template, the structure of the empty solid exhibited permanent microporosity (S _BET = 342 m² g^–1). Being a true molecular sponge, the channel framework of this material allowed the inclusion of a variety of molecular sample guests without compromising its crystalline nature. Remarkably, this crystalline material enabled the structure determination by X-ray diffraction of the included molecules. Theoretical studies demonstrated the vital role played by the dispersive forces in the overall stabilization of the crystal packing.     

Accurate molecular weight determination of small molecules via DOSY-NMR by using external calibration curves with normalized diffusion coefficients

Determination of the aggregation and solvation numbers of organometallic complexes in solution is an important task to increase insight in reaction mechanisms. Thus knowing which aggregates are formed during a reaction is of high interest to develop better selectivity and higher yields. Diffusion-ordered spectroscopy (DOSY), which separates NMR signals according to the diffusion coefficient, finds increasing use to identify species in solution. However, there still is no simple relationship between diffusion coefficient and molecular weight (MW). Some methods have been developed to estimate the MW but still with a significant error of ±30%. Here we describe a novel development of MW-determination by using an external calibration curve (ECC) approach with normalized diffusion coefficients. Taking the shape of the molecules into account enables accurate MW-predictions with a maximum error of smaller than ±9%. Moreover we show that the addition of multiple internal references is dispensable. One internal reference (that also can be the solvent) is sufficient. If the solvent signal is not accessible, 16 other internal standards (aliphatics and aromatics) are available to avoid signal overlapping problems and provide flexible choice of analytes. This method is independent of NMR-device properties and diversities in temperature or viscosity and offers an easy and robust method to determine accurate MWs in solution.     

Synthesis and reaction of a new type of 5-deazaflavin with axial and planar chirality

A new type of 5-deazaflavin derivative with axial and planar chirality was synthesized as a flavoenzyme model. A novel optical resolution gave an enantiomeric pair of the 5-deazaflavins 1a,b. Compounds1a,b were optically stable and effectively discriminated PNPH enantiomers in a model reaction of intercoenzyme hydrogen transfer.     

Self-assembling 1D core/shell microrods by the introduction of additives: a one-pot and shell-tunable method

Herein, we have developed a one-pot method for the fabrication of one-dimensional core/shell microrods with tunable shell compositions by the introduction of additives. Crystalline dimethyl melamine hydrochloride was utilized as the core, while melamine derivatives with different functional groups, such as pyrene, thiophene and naphthalene diimide, served as additives to regulate the core morphology and were adsorbed as the shell. The length and width of these one-dimensional structures can be tuned by varying the molar ratio of core and shell molecules as well as their total concentration. Through X-ray diffraction, the detailed molecular arrangements within the core of the microrods were revealed, and the selective effect of additives on specific crystal faces was evaluated. It is anticipated that this work may provide a facile approach for the fabrication of one-dimensional functional materials.     

Diazo compounds for the bioreversible esterification of proteins

A diazo compound is shown to convert carboxylic acids to esters efficiently in an aqueous environment. The basicity of the diazo compound is critical: low basicity does not lead to a reaction but high basicity leads to hydrolysis. This reactivity extends to carboxylic acid groups in a protein. The ensuing esters are hydrolyzed by human cellular esterases to regenerate protein carboxyl groups. This new mode of chemical modification could enable the key advantages of prodrugs to be translated from small-molecules to proteins.     

Absolute determination method using chirality for glufosinate and bialaphos by gamma-cyclodextrin modified capillary zone electrophoresis.

A novel absolute determination method using chirality without any calibration curves or comparison standards has been proposed for phosphorus-containing amino acid-type herbicides, glufosinate (D,L-GLUF) and bialaphos (BIAL). This method is based on a change in the enantiomeric ratio after the spiking of a known amount of the enantiomers with different enantiomeric ratios to a sample. D,L-GLUF was determined by adding a known amount of L-GLUF to the sample, derivatizing them with dansyl chloride, and measuring the ratio of the peak area of the D-isomer to that of the L-isomer by means of gamma-cyclodextrin modified capillary zone electrophoresis. The accuracy and precision of the method were evaluated using a synthetic sample. The mean values obtained for D- and L-GLUF agreed with the values taken within 1.6%; also the reproducibility was as good as less than 2.8%. The determination of BIAL was achieved by determining GLUF quantitatively produced by the acid hydrolysis of BIAL. The proposed methods were applied to the analysis of commercial herbicides and the validity and usefulness were evaluated.     

Structural studies and binding properties of pendant diazacoronands—precursors to macrocyclic compounds of planar chirality

Structural studies of pendant diazacoronands having an N-benzoyl, N-acetyl, O-benzyl or O-benzoyl side arm were performed by means of X-ray and temperature-dependent ¹H NMR experiments. The energies of macroring flipping process were determined for three pendant diazacoronands. The complexation properties of pendant diazacoronands toward the alkali metal cations (Na⁺, K⁺, and Rb⁺) were estimated by ESI-MS experiments.     

17O NMR spectroscopy of crystalline microporous materials

Microporous materials, containing pores and channels of similar dimensions to small molecules have a range of applications in catalysis, gas storage and separation and in drug delivery. Their complex structure, often containing different types and levels of positional, compositional and temporal disorder, makes structural characterisation challenging, with information on both long-range order and the local environment required to understand the structure–property relationships and improve the future design of functional materials. In principle, ¹⁷O NMR spectroscopy should offer an ideal tool, with oxygen atoms lining the pores of many zeolites and phosphate frameworks, playing a vital role in host–guest chemistry and reactivity, and linking the organic and inorganic components of metal–organic frameworks (MOFs). However, routine study is challenging, primarily as a result of the low natural abundance of this isotope (0.037%), exacerbated by the presence of the quadrupolar interaction that broadens the spectral lines and hinders the extraction of information. In this Perspective, we will highlight the current state-of-the-art for ¹⁷O NMR of microporous materials, focusing in particular on cost-effective and atom-efficient approaches to enrichment, the use of enrichment to explore chemical reactivity, the challenge of spectral interpretation and the approaches used to help this and the information that can be obtained from NMR spectra. Finally, we will turn to the remaining challenges, including further improving sensitivity, the high-throughput generation of multiple structural models for computational study and the possibility of in situ and in operando measurements, and give a personal perspective on how these required improvements can be used to help solve important problems in microporous materials chemistry.

Cost-effective and atom-efficient isotopic enrichment enables ¹⁷O NMR spectroscopy of microporous materials to be used to probe local structure and disorder and to explore chemical reactivity.     

Synthesis of cyclophanes with planar and helical chirality

Novel helical macrocyclic imines derived from planar chiral [2.2]paracyclophane were synthesized. The chiroptical properties of the enantiopure compounds were investigated and their absolute configurations were assigned.     

CIT-7, a crystalline,molecular sieve with pores bounded by 8 and 10-membered rings

A new crystalline molecular sieve, denoted CIT-7, is synthesized using an imidazolium-based diquaternary organic structure directing agent (OSDA). The framework structure is determined from a combination of rotation electron diffraction and synchrotron X-ray powder diffraction data. The structure has 10 crystallographically unique tetrahedral atoms (T-atoms) in the unit cell, and can be described as an ordered arrangement of the [4²5⁴6²] mtw building unit and a previously unreported [4⁴5²] building unit. The framework contains a 2-dimensional pore system that is bounded by 10 T-atom rings (10-ring, 5.1 Å × 6.2 Å opening) that are connected with oval 8-rings (2.9 Å × 5.5 Å opening) through medium-sized cavities (∼7.9 Å) at the channel intersections. CIT-7 can be synthesized over a broad range of compositions including pure-silica and heteroatom, e.g., aluminosilicate and titanosilicate, containing variants.     

Polarity and structure of eight-membered organosilicon compounds with planar fragments

For the first time is determined the polarity of eight-membered silocyns with planar fragments. By the methods of dipole moments and theoretical calculations (DFT B3LYP/6-31G*) of 1,3,2-dioxasilocyns is established that in these compounds occurs the conformational equilibrium of the forms bath-chair and distorted bath with the predominance of the first, in this case the bonds C(sp ³)-S and C(sp ³)-H of the exocyclic MeSCH₂ group are in the not eclipsed gauche orientation relative to each other.     

Applications of dynamic combinatorial chemistry for the determination of effective molarity

A new strategy for determining thermodynamic effective molarities (EM) for macrocylisation reactions using dynamic combinatorial chemistry under dilute conditions is presented. At low concentrations, below the critical value, Dynamic Libraries (DLs) of bifunctional building blocks contain only cyclic species, so it is not possible to quantify the equilibria between linear and cyclic species. However, addition of a monofunctional chain stopper can be used to promote the formation of linear oligomers allowing measurement of EM for all cyclic species present in the DL. The effectiveness of this approach was demonstrated for DLs generated from mixtures of 1,3-diimine calix[4]arenes, linear diaminoalkanes and monoaminoalkanes. For macrocycles deriving from one bifunctional calixarene and one diamine, there is an alternating pattern of EM values with the number of methylene units in the diamine: odd numbers give significantly higher EMs than even numbers. For odd numbers of methylene units, the alkyl chain can adopt an extended all anti conformation, whereas for even numbers of methylene units, gauche conformations are required for cyclisation, and the associated strain reduces EM. The value of EM for the five-carbon linker indicates that this macrocycle is a strainless ring.     

Synthesis and structural analysis of nonstoichiometric ternary fulleride K 1.5 Ba 0.25 CsC 60

The existence of cation-vacancy sites in fullerides might lead to long-range ordering and generate a new vacancy-ordered superstructure. The purpose of this work is to search whether or not long-range ordering of vacant tetrahedral sites, namely superstructure emerges in nonstoichiometric K _1.5 Ba _0.25 CsC ₆₀ fulleride. Therefore, K _1.5 Ba _0.25 CsC ₆₀ with cation-vacancy sites is synthesized using a precursor method to avoid inadequate stoichiometry control and formation of impurity phases within the target composition. For this purpose, first, phase-pure K ₆ C ₆₀ , Ba ₆ C ₆₀ and Cs ₆ C ₆₀ precursors are synthesized. Stoichiometric quantities of these precursors are used for further reaction with C ₆₀ to afford K _1.5 Ba _0.25 CsC ₆₀ . Rietveld analysis of the high-resolution synchrotron X-ray powder diffraction data of the precursors and K _1.5 Ba _0.25 CsC ₆₀ confirms that K ₆ C ₆₀ , Ba ₆ C ₆₀ and Cs ₆ C ₆₀ are single-phase and they crystallize in a body-centered-cubic structure ( Im 3) as reported in the literature. The analysis also shows that K _1.5 Ba _0.25 CsC ₆₀ phase can be perfectly modeled using a face-centered cubic structure. No new peaks appear which could have implied the appearance of a superstructure. This suggests that there is no long-range ordered arrangement of vacant tetrahedral sites in K _1.5 Ba _0.25 CsC ₆₀ .     

Solid state crystalline and liquid crystalline structure of semifluorinated 1-bromoalkane compounds

A series of semifluorinated 1-bromoalkane (SFBA) mesogens have been synthesized and characterized to better understand their solid state crystalline and liquid crystalline structures. In the solid state, the local conformation of the fluorocarbon segments becomes disordered once the fluorocarbon chain reaches a length above eight CF units. This is evident from the pronounced decrease of molar melting enthalpy. An increasing amount of helix and helix reverse conformations and increasingly disordered packing can also be observed with each addition of a fluorocarbon segment. X-ray diffraction peaks in the small angle region can be indexed by a tilted, two dimensional layered (herring bone) structure. The crystal structure is similar to a type of plastic crystal in which the amphiphilic character is clear, because the two segments of fluorocarbon and hydrocarbon are almost immiscible. Heating of F(CF2)12(CH2)10Br leads to a transition from plastic crystal to smectic B, as revealed by time-resolved XRD and FTIR analysis. At this solid-to-liquid transition temperature, conformational analysis confirmed an onset of the CH2 gauche conformation within the hexagonal lattice, most likely due to changes occurring in the hydrocarbon segment, and a sudden increase of helix defects along the fluorocarbon segment. The disordered helix rigid-rod structure of the fluorocarbon segment and its poor compatibility with the hydrocarbon segment play an important role in the crystalline solid and liquid crystalline structures.     

Thermal and photochemical transformation of conformational chirality into configurational chirality in the crystalline state

Because they crystallize in chiral conformations in which abstraction of only one of two diastereotopic gamma-hydrogen atoms is possible, salts formed between achiral keto-acids possessing the tricyclo[4.4.1.0]undecane ring system and optically pure amines undergo Norrish type II cleavage in the solid state in enantiomeric excesses as high as 95% at 98% conversion, following removal of the ionic chiral auxiliaries. Thermal enolene rearrangement of the same salts results in optical yields approximately half those observed for the photochemical reaction.     

New chiral zinc complexes: synthesis, structure, and induction of axial chirality

We describe an efficient methodology for the preparation of new chiral zinc complexes by assembling dynamically racemic biphenol derivatives and chiral 1,2-diamines with suitable zinc(II) precursors. Mononuclear and dinuclear zinc(II) complexes were formed from differently substituted biphenols. The solid-state and solution structural characterization of the resulting compounds allowed us to demonstrate a preferential sense of induced axial chirality for mononuclear complexes, a phenomenon that was not observed for the dinuclear ones.     

In situ activation and monitoring of the evolution of the intracellular caspase family

The evolution of the intracellular caspase family is crucial in cell apoptosis. To evaluate this process, a universal platform of in situ activation and monitoring of the evolution of intracellular caspase is designed. Using well-known gold nanostructure as a model of both nanocarrier and matter inducing the cell apoptosis for photothermal therapy, a nanoprobe is prepared by assembly of two kinds of dye-labelled peptides specific to upstream caspase-9 and downstream caspase-3 as the signal switch, and folic acid as a targeting moiety. The energy transfer from dyes to the gold nanocarrier at two surface plasmon resonance absorption wavelengths leads to their fluorescence quenching. Upon endocytosis of the nanoprobe to perform the therapy against cancer cells, the peptides are successively cleaved by intracellular caspase activation with the evolution from upstream to downstream, which lights up the fluorescence of the dyes sequentially, and can be used to quantify both caspase-9 and caspase-3 activities in cancer cells and to monitor their evolution in living mice. The recovered fluorescence could also be used to assess therapeutic efficiency. This work provides a novel powerful tool for studying the evolution of the intracellular caspase family and elucidating the biological roles of caspases in cancer cell apoptosis.