Chemistry

Wollastonite (CaSiO₃) is an important mineral that is widely used in ceramics and polymer industries. Defect energetics, diffusion of Ca ions and a solution of dopants are studied using atomistic-scale simulation based on the classical pair potentials. The energetically favourable defect process is calculated to be the Ca-Si anti-site defect cluster in which both Ca and Si swap their atomic positions simultaneously. It is calculated that the Ca ion migrates in the ab plane with an activation energy of 1.59 eV, inferring its slow diffusion. Favourable isovalent dopants on the Ca and Si sites are Sr²⁺ and Ge⁴⁺, respectively. Subvalent doping by Al on the Si site is a favourable process to incorporate additional Ca in the form of interstitials in CaSiO₃. This engineering strategy would increase the capacity of this material. Full article

A model for the survival of the amino acid content in micrometeorites and its possible transformations upon atmospheric entry is described. Since any organic species released in the atmosphere at high altitudes would exhibit a limited lifetime with respect to the typical timescale for atmospheric mixing (due to the substantial radiation field of the early Sun), only the organic content inside the meteorites could have contributed to prebiotic chemistry. It is thus important to determine both the amino acid loss from meteorites, due to both degassing and chemical degradation, and the extent of the chemical transformation of amino acids subjected to the increased temperature due to friction with the atmosphere. According to the interplay between the potential energy barrier and the pre-exponential factor in rate coefficients, either diffusion or chemical processing might be the dominant process following the rising temperature upon atmospheric entry. The possibility of the elimination of water from glycine to form aminoketene, or ${\mathrm{CO}}_2$ to form methylamine, ultimately driven by gravitational energy, was examined along with the more conventional formation of a peptide bond between two glycine units to afford Gly–Gly. While retention, degassing, and decarboxylation are the fastest processes, each dominating in different ranges of the initial velocity and radius, the formation of either Gly–Gly from bimolecular water elimination or aminoketene from unimolecular water elimination appears to be negligible. Full article

The synthesis and corrosion inhibition performance of poly(butylene-succinate)-L-proline (PBSLP) prepared by solution polymerization are reported. PBSLP was characterized by FTIR, XRD, and SEM/energy dispersive X-ray (EDX). PBSLP was used to protect mild steel in 1 M hydrochloric acid. An SEM and an atomic force microscope (AFM) were used to characterize the surface morphology of the mild steel coupons. Potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) were used to characterize the inhibition mechanism of PBSLP, and the inhibitor was a mixed-type corrosion inhibitor with a maximum corrosion inhibition efficiency of 93.0%. Adsorption studies revealed the adsorption of PBSLP to be a monolayer process and therefore, obeyed the Langmuir isotherm model. Full article

Traditional organic antimicrobials mainly act on specific biochemical processes such as replication, transcription and translation. However, the emergence and wide spread of microbial resistance is a growing threat for human beings. Therefore, it is highly necessary to design strategies for the development of new drugs in order to target multiple cellular processes that should improve their efficiency against several microorganisms, including bacteria, viruses or fungi. The present review is focused on recent advances and findings of new antimicrobial strategies based on metal complexes. Recent studies indicate that some metal ions cause different types of damages to microbial cells as a result of membrane degradation, protein dysfunction and oxidative stress. These unique modes of action, combined with the wide range of three-dimensional geometries that metal complexes can adopt, make them suitable for the development of new antimicrobial drugs. Full article

The large originator pharmaceutical companies need more and more new compounds for their molecule banks, because high throughput screening (HTS) is still a widely used method to find new hits in the course of the lead discovery. In the design and synthesis of a new compound library, important points are in focus nowadays: Lipinski’s rule of five (RO5); the high Fsp³ character; the use of bioisosteric heterocycles instead of aromatic rings. With said aim in mind, we have synthesized a small compound library of new spiro[cycloalkane-pyridazinones] with 36 members. The compounds with this new scaffold may be useful in various drug discovery projects. Full article

This work establishes the ‘click’ nature of the base-catalyzed oxirane ring opening reaction by the selenolate nucleophile. The ‘click’-generated ß-hydroxy selenide can be alkylated to afford cationic selenium species. Hemolytic studies suggest that selenonium cations do not lyse red blood cells even at high concentrations. Overall, these results indicate the future applicability of the developed organo-selenium chemistry in the preparation of a new class of cationic materials based on the seleno-ether motif. Full article

The crystal structures of inorganic hydroborates (salts and coordination compounds with anions containing hydrogen bonded to boron) except for the simplest anion, borohydride BH₄⁻, are analyzed regarding their structural prototypes found in the inorganic databases such as Pearson’s Crystal Data [Villars and Cenzual (2015), Pearson’s Crystal Data. Crystal Structure Database for Inorganic Compounds, Release 2019/2020, ASM International, Materials Park, Ohio, USA]. Only the compounds with hydroborate as the only type of anion are reviewed, although including compounds gathering more than one different hydroborate (mixed anion). Carbaborane anions and partly halogenated hydroborates are included. Hydroborates containing anions other than hydroborate or neutral molecules such as NH₃ are not discussed. The coordination polyhedra around the cations, including complex cations, and the hydroborate anions are determined and constitute the basis of the structural systematics underlying hydroborates chemistry in various variants of anionic packing. The latter is determined from anion–anion coordination with the help of topology analysis using the program TOPOS [Blatov (2006), IUCr CompComm. Newsl. 7, 4–38]. The Pauling rules for ionic crystals apply only to smaller cations with the observed coordination number within 2–4. For bigger cations, the predictive power of the first Pauling rule is very poor. All non-molecular hydroborate crystal structures can be derived by simple deformation of the close-packed anionic lattices, i.e., cubic close packing (ccp) and hexagonal close packing (hcp), or body-centered cubic (bcc), by filling tetrahedral or octahedral sites. This review on the crystal chemistry of hydroborates is a contribution that should serve as a roadmap for materials engineers to design new materials, synthetic chemists in their search for promising compounds to be prepared, and materials scientists in understanding the properties of novel materials. Full article

The Flack Parameter is now almost universally reported for all chiral materials characterized by X-ray crystallography. Its elegant simplicity was an inspired development by Howard Flack, and although the original algorithm for its computation has been strengthened by other workers, it remains an essential outcome for any crystallographic structure determination. As with any one-parameter metric, it needs to be interpreted in the context of its standard uncertainty. Full article

This perspective is focused on the main parameters determining the results of crystallization of enantiomers or enantiomeric mixtures. It was shown that the ratio of supramolecular and helical associations depends on the eutectic composition of the corresponding enantiomeric mixture. The M and P ratios together with the self-disproportionation (SDE) of enantiomers define the reaction of the racemic compound with the resolving agent. Eventually, each chiral molecule reacts with at least two conformers with different degrees of M and P helicity. The combined effect of the configuration, charge distribution, constituent atoms, bonds, flexibility, and asymmetry of the molecules influencing their behavior was also summarized. Full article

Ab initio structure determination of new metal-organic framework (MOF) compounds is generally done by single crystal X-ray diffraction, but this technique can yield incorrect crystal structures if crystal twinning is overlooked. Herein, the crystal structures of three Zirconium-based MOFs, that are especially prone to twinning, have been determined from twinned crystals. These twin laws (and others) could potentially occur in many MOFs or related network structures, and the methods and tools described herein to detect and treat twinning could be useful to resolve the structures of affected crystals. Our results highlight the prevalence (and sometimes inevitability) of twinning in certain Zr-MOFs. Of special importance are the works of Howard Flack which, in addition to fundamental advances in crystallography, provide accessible tools for inexperienced crystallographers to take twinning into account in structure elucidation. Full article

Chiral compounds have played an important role in the development of coordination chemistry. Unlike organic chemistry, where mechanistic rules allowed the establishment of absolute configurations for numerous compounds once a single absolute determination had been made, coordination compounds are more complex. This article discusses the development of crystallographic methods and the interplay with coordination chemistry. Most importantly, the development of the Flack parameter is identified as providing a routine method for determining the absolute configuration of coordination compounds. Full article

As catalysis plays a significant role in the development of economical and sustainable chemical processes, increased attention is paid to the recovery and reuse of high-value catalysts. Although homogeneous catalysts are usually more active and selective than the heterogeneous ones, both catalyst recycling and product separation pose a challenge for developing industrially feasible methods. In this respect, membrane-supported recovery of organocatalysts represents a particularly useful tool and a valid option for organocatalytic asymmetric synthesis. However, catalyst leaching/degradation and a subsequent decrease in selectivity/conversion are significant drawbacks. As the effectivity of the membrane separation depends mainly on the size of the catalyst in contrast to the other solutes, molecular weight enlargement of small organocatalysts is usually necessary. In the last few years, several synthetic methodologies have been developed to facilitate their recovery by nanofiltration. With the aim of extending the possibilities for the membrane-supported recovery of organocatalysts further, this contribution presents a review of the existing synthetic approaches for the molecular weight enlargement of organocatalysts. Full article

Four enantiomeric forms of natural prostaglandins, ent-PGF_2α ((−)-1), ent-PGE₂ ((+)-2) ent-PGF_1α ((−)-3), and ent-PGE₁ ((+)-4) have been synthetized in gram scale by Corey synthesis used in the prostaglandin plants of CHINOIN, Budapest. Chiral HPLC methods have been developed to separate the enantiomeric pairs. Enantiomers of natural prostaglandins can be used as analytical standards to verify the enantiopurity of synthetic prostaglandins, or as biomarkers to study oxidation processes in vivo. Full article

The antitumor indole–indoline alkaloids of the evergreen Catharanthus roseus—namely vinblastine and vincristine—are widely used in chemotherapy of cancer. Many efforts were made to synthesize more efficient derivatives with less side-effect. The 14,15-cyclopropane derivative of vinblastine was synthesized successfully by a five-step procedure starting from vindoline. Vincristine, vinorelbine and several derivatives condensed with a cyclopropane ring were synthesized. Various hybrid molecules were prepared by the coupling reaction of vindoline and methyl ester of tryptophan, which were conjugated by carrier peptides of octaarginine. Studying the halogenation reactions of vindoline and catharanthine some fluorine derivatives were obtained which showed promising antitumor activity on various tumor types. The synthesis of the Aspidospermane alkaloid bannucine and 5′-epibannucine were carried out using N-acyliminium intermediates. The same intermediate was also applied in the first synthesis of sessiline. The research group have synthesized of flavonoid alkaloids: dracocephins A and B. Further three flavonoid alkaloids, namely 8-(2”-pyrrolidinon-5′′-yl)quercetin, 6-(2′′-pyrrolidinon-5′′-yl)-(−)- and 8-(2′′-pyrrolidinon-5′′-yl)-(−)-epicatechin were prepared by acid-catalyzed regioselective Mannich reaction starting from the corresponding flavonoid precursor. Vindoline was also coupled to synthetic pharmacophores, such as triphenylphosphine and various N-heterocycles. Some of these hybrid molecules showed significant antitumor activity. Furthermore, 7-OH and 7-NH modified flavonoid derivatives were synthesized by a regioselective alkylation followed by Smiles rearrangement and hydrolysis. Full article

A new class of six mono- (1; 3-Cl-, 2; 5-Cl-, 3; 6-Cl-) and di-(4; 3,6-Cl, 5; 5,6-Cl-, 6; 3,5-Cl-) chloro-substituted pyrazin-2-amine ligands (1–6) form complexes with copper (I) bromide, to give 1D and 2D coordination polymers through a combination of halogen and hydrogen bonding that were characterized by X-ray diffraction analysis. These Cu(I) complexes were prepared indirectly from the ligands and CuBr₂ via an in situ redox process in moderate to high yields. Four of the pyrazine ligands, 1, 4–6 were found to favor a monodentate mode of coordination to one Cu^I ion. The absence of a C6-chloro substituent in ligands 1, 2 and 6 supported N1–Cu coordination over the alternative N4–Cu coordination mode evidenced for ligands 4 and 5. These monodentate systems afforded predominantly hydrogen bond (HB) networks containing a catenated (μ₃-bromo)-Cu^I ‘staircase’ motif, with a network of ‘cooperative’ halogen bonds (XB), leading to infinite polymeric structures. Alternatively, ligands 2 and 3 preferred a μ₂-N,N’ bridging mode leading to three different polymeric structures. These adopt the (μ₃-bromo)-Cu^I ‘staircase’ motif observed in the monodentate ligands, a unique single (μ₂-bromo)-Cu^I chain, or a discrete Cu₂Br₂ rhomboid (μ₂-bromo)-Cu^I dimer. Two main HB patterns afforded by self-complimentary dimerization of the amino pyrazines described by the graph set notation R₂²(8) and non-cyclic intermolecular N–H∙∙∙N’ or N–H∙∙∙Br–Cu leading to infinite polymeric structures are discussed. The cooperative halogen bonding between C–Cl∙∙∙Cl–C and the C–Cl∙∙∙Br–Cu XB contacts are less than the sum of the van der Waals radii of participating atoms, with the latter ranging from 3.4178(14) to 3.582(15) Å. In all cases, the mode of coordination and pyrazine ring substituents affect the pattern of HBs and XBs in these supramolecular structures. Full article

Halogenated carboxylic acids have been important compounds in chemical synthesis and indispensable research tools in biochemical studies for decades. Nevertheless, the number of structurally characterized simple α-brominated monocarboxylic acids is still limited. We herein report the crystallization and structural elucidation of (R)- and rac-2-bromo-3-methylbutyric acid (2-bromo-3-methylbutanoic acid, 1) to shed light on intermolecular interactions, in particular hydrogen bonding motifs, packing modes and preferred conformations in the solid-state. The crystal structures of (R)- and rac-1 are revealed by X-ray crystallography. Both compounds crystallize in the triclinic crystal system with Z = 2; (R)-1 exhibits two crystallographically distinct molecules. In the crystal, (R)-1 forms homochiral O–H···O hydrogen-bonded carboxylic acid dimers with approximate non-crystallographic C₂ symmetry. In contrast, rac-1 features centrosymmetric heterochiral dimers with the same carboxy syn···syn homosynthon. The crystal packing of centrosymmetric rac-1 is denser than that of its enantiopure counterpart (R)-1. The molecules in both crystal structures adopt a virtually identical staggered conformation, despite different crystal environments, which indicates a preferred molecular structure of 1. Intermolecular interactions apart from classical O–H···O hydrogen bonds do not appear to have a crucial bearing on the solid-state structures of (R)- and rac-1. Full article

1,2,4-Benzothiadiazine 1,1-dioxide derivatives (e.g., chlorothiazide, hydrochlorothiazide) have been long used in the human therapy as diuretic and antihypertensive agents. Marketed drugs containing the structurally related phthalazinone scaffold are applied for the treatment of various diseases ranging from ovarian cancer to diabetes and allergy. 1,2,3-Benzothiadiazine 1,1-dioxides combine the structural features of these two compound families, which led to their more intensive research since the 1960s. In the present review, we summarize the literature of this period of more than half a century, including all scientific papers and patent applications dealing with the synthesis and reactions of this compound family, briefly hinting at their potential therapeutic application as well. Full article

Intercellular gap junction (GJ) contacts formed by the coupling of connexin (Cx) hemichannels (HCs) embedded into the plasma membranes of neighboring cells play significant role in the development, signaling and malfunctions of mammalian tissues. Understanding and targeting GJ functions, however, calls for finding valid Cx subtype-specific inhibitors. We conjecture the lack of information about binding interactions between the GJ interface forming extracellular EL1 and EL2 loops and peptide mimetics designed to specifically inhibit Cx43HC coupling to Cx43GJ. Here, we explore active spots at the GJ interface using known peptide inhibitors that mimic various segments of EL1 and EL2. Binding interactions of these peptide inhibitors and the non-peptide inhibitor quinine has been modelled in combination with the use of blind docking molecular mechanics (MM). The neuron-specific Cx36HC and astrocyte-specific Cx43HC subtypes were modelled with a template derived from the high-resolution structure of Cx26GJ. GJ-coupled and free Cx36HC and Cx43HC models were obtained by dissection of GJs (GJ-coupled) followed by 50 ns molecular dynamics (free). Molecular mechanics (MM) calculations were performed by the docking of inhibitors, explicitly the designed Cx43 EL1 or EL2 loop sequence mimetics (GAP26, P5 or P180–195, GAP27, Peptide5, respectively) and the Cx36 subtype-specific quinine into the model structures. In order to explore specific binding interactions between inhibitors and CxHC subtypes, MM/Generalized Born Surface Area (MM/GBSA) ΔG_bind values for representative conformers of peptide mimetics and quinine were evaluated by mapping the binding surface of Cx36HC and Cx43HC for all inhibitors. Quinine specifically contacts Cx36 EL1 residues V54-C55-N56-T57-L58, P60 and N63. Blocking the vestibule by the side of Cx36HC entry, quinine explicitly interacts with the non-conserved V54, L58, N63 residues of Cx36 EL1. In addition, our work challenges the predicted specificity of peptide mimetics, showing that the docking site of peptides is unrelated to the location of the sequence they mimic. Binding features, such as unaffected EL2 residues and the lack of Cx43 subtype-specificity of peptide mimetics, suggest critical roles for peptide stringency and dimension, possibly pertaining to the Cx subtype-specificity of peptide inhibitors. Full article

The one-pot multistep ethyltellurenylation reaction of epoxides with elemental tellurium and lithium triethylborohydride is described. The reaction mechanism was experimentally investigated. Dilithium ditelluride and triethyl borane, formed from elemental tellurium and lithium triethylborohydride, were shown to be the key species involved in the reaction mechanism. Epoxides undergo ring-opening reaction with dilithium ditelluride to afford β-hydroxy ditellurides, which are sequentially converted into the corresponding β-hydroxy-alkyl ethyl tellurides by transmetalation with triethyl borane, reasonably proceeding through the S_H2 mechanism. Full article