Chemistry — An International Journal

LAMP is an approach for isothermal nucleic acids diagnostics with increasing importance but suffers from the need of tedious systems design and optimization for every new target. Here, we describe an approach for its simplification based on a single nucleoside-5′-O-triphosphate (dNTP) that is covalently modified with a DNA strand. We found that the DNA-modified dNTP is a substrate for DNA polymerases in versatile primer extension reactions despite its size and that the incorporated DNA indeed serves as a target for selective LAMP analysis. Full article

In nature, various specific reactions only occur in spatially controlled environments. Cell compartment and subcompartments act as the support required to preserve the bio-specificity and functionality of the biological content, by affording absolute segregation. Inspired by this natural perfect behavior, bottom-up approaches are on focus to develop artificial cell-like structures, crucial for understanding relevant bioprocesses and interactions or to produce tailored solutions in the field of therapeutics and diagnostics. In this review, we discuss the benefits of constructing polymer-based single and multicompartments (capsules and giant unilamellar vesicles (GUVs)), equipped with biomolecules as to mimic cells. In this respect, we outline key examples of how such structures have been designed from scratch, namely, starting from the application-oriented selection and synthesis of the amphiphilic block copolymer. We then present the state-of-the-art techniques for assembling the supramolecular structure while permitting the encapsulation of active compounds and the incorporation of peptides/membrane proteins, essential to support in situ reactions, e.g., to replicate intracellular signaling cascades. Finally, we briefly discuss important features that these compartments offer and how they could be applied to engineer the next generation of microreactors, therapeutic solutions, and cell models. Full article

Pyrimidine cyclobutane dimers are hazardous DNA lesions formed upon exposure of DNA to UV light, which can be repaired through oxidative electron transfer (ET). Laser flash photolysis and computational studies were performed to explore the role of configuration and constitution at the cyclobutane ring on the oxidative repair process, using the nitrate radical (NO₃^•) as oxidant. The rate coefficients of 8–280 × 10⁷ M⁻¹ s⁻¹ in acetonitrile revealed a very high reactivity of the cyclobutane dimers of N,N’-dimethylated uracil (DMU), thymine (DMT), and 6-methyluracil (DMU^6-Me) towards NO₃^•, which likely proceeds via ET at N(1) as a major pathway. The overall rate of NO₃^• consumption was determined by (i) the redox potential, which was lower for the syn- than for the anti-configured dimers, and (ii) the accessibility of the reaction site for NO₃^•. In the trans dimers, both N(1) atoms could be approached from above and below the molecular plane, whereas in the cis dimers, only the convex side was readily accessible for NO₃^•. The higher reactivity of the DMT dimers compared with isomeric DMU dimers was due to the electron-donating methyl groups on the cyclobutane ring, which increased their susceptibility to oxidation. On the other hand, the approach of NO₃^• to the dimers of DMU^6-Me was hindered by the methyl substituents adjacent to N(1), making these dimers the least reactive in this series. Full article

Antimicrobial resistance is an increasingly serious threat to global public health that requires innovative solutions to counteract new resistance mechanisms emerging and spreading globally in infectious pathogens. Classic organic antibiotics are rapidly exhausting the structural variations available for an effective antimicrobial drug and new compounds emerging from the industrial pharmaceutical pipeline will likely have a short-term and limited impact before the pathogens can adapt. Inorganic and organometallic complexes offer the opportunity to discover and develop new active antimicrobial agents by exploiting their wide range of three-dimensional geometries and virtually infinite design possibilities that can affect their substitution kinetics, charge, lipophilicity, biological targets and modes of action. This review describes recent studies on the antimicrobial activity of transition metal complexes of groups 6–12. It focuses on the effectiveness of the metal complexes in relation to the rich structural chemical variations of the same. The aim is to provide a short vade mecum for the readers interested in the subject that can complement other reviews. Full article

Radical-mediated lipid oxidation and the formation of lipid hydroperoxides has been a focal point in the investigation of a number of human pathologies. Lipid peroxidation has long been linked to the inflammatory response and more recently, has been identified as the central tenet of the oxidative cell death mechanism known as ferroptosis. The formation of lipid electrophile-protein adducts has been associated with many of the disorders that involve perturbations of the cellular redox status, but the identities of adducted proteins and the effects of adduction on protein function are mostly unknown. Both cholesterol and 7-dehydrocholesterol (7-DHC), which is the immediate biosynthetic precursor to cholesterol, are oxidizable by species such as ozone and oxygen-centered free radicals. Product mixtures from radical chain processes are particularly complex, with recent studies having expanded the sets of electrophilic compounds formed. Here, we describe recent developments related to the formation of sterol-derived electrophiles and the adduction of these electrophiles to proteins. A framework for understanding sterol peroxidation mechanisms, which has significantly advanced in recent years, as well as the methods for the study of sterol electrophile-protein adduction, are presented in this review. Full article

The properties of several hydrazon-diketone rotary switches with OH groups in the stators (2-(2-(2-hydroxy-4-nitrophenyl)hydrazono)-1-phenylbutane-1,3-dione, 2-(2-(2-hydroxyphenyl)hydrazono)-1-phenylbutane-1,3-dione and 2-(2-(4-hydroxyphenyl)hydrazono)-1-phenylbutane-1,3-dione) were investigated by molecular spectroscopy (UV-Vis and NMR), DFT calculations (M06-2X/TZVP) and X-ray analysis. The results show that, when the OH group is in ortho position, the E’ and Z’ isomers are preferred in DMSO as a result of a stabilizing intermolecular hydrogen bonding with the solvent. The availability, in addition, of a nitro group in para position increases the possibility of deprotonation of the OH group in the absence of water. All studied compounds showed a tendency towards formation of associates. The structure of the aggregates was revealed by theoretical calculation and confirmed by X-ray analysis. Full article

Recent progress in wood preservative research has led to the use of insoluble copper carbonate in the form of nano- to micron-sized particles in combination with known triazole fungicides to combat fungal decay and thus decrease physical material properties. Evidently, particle-based agents could lead to issues regarding impregnation of a micro-structured material like wood. In this study, we analyzed these limitations via silicon dioxide particles in impregnation experiments of pine and beech wood. In our experiments, we showed that limitations already existed prior to assumed particle size thresholds of 400–600 nm. In pine wood, 70 nm sized particles were efficiently impregnated, in contrast to 170 nm particles. Further we showed that surface functionalized silica nanoparticles have a major impact on the impregnation efficiency. Silica surfaces bearing amino groups were shown to have strong interactions with the wood cell surface, whereas pentyl chains on the SiO₂ surfaces tended to lower the particle–wood interaction. The acquired results illustrate an important extension of the currently limited knowledge of nanoparticles and wood impregnation and contribute to future improvements in the field of particle-based wood preservatives. Full article

A method is presented for the direct computation of hydrocarbon strain energies using computational group equivalents. Parameters are provided at several high levels of electronic structure theory: W1BD, G-4, CBS-APNO, CBS-QB3, and M062X/6-31+G(2df,p). As an illustration of the procedure, strain energies are computed for 66 hydrocarbons, most of them highly strained. Full article

As the only enzyme currently known to reduce dinitrogen (N₂) to ammonia (NH₃), nitrogenase is of significant interest for bio-inspired catalyst design and for new biotechnologies aiming to produce NH₃ from N₂. In order to reduce N₂, nitrogenase must also hydrolyze at least 16 equivalents of adenosine triphosphate (MgATP), representing the consumption of a significant quantity of energy available to biological systems. Here, we review natural and engineered electron transfer pathways to nitrogenase, including strategies to redirect or redistribute electron flow in vivo towards NH₃ production. Further, we also review strategies to artificially reduce nitrogenase in vitro, where MgATP hydrolysis is necessary for turnover, in addition to strategies that are capable of bypassing the requirement of MgATP hydrolysis to achieve MgATP-independent N₂ reduction. Full article

Two classes of mechanically interlocked molecules, [3]rotaxanes and knotted [1]rotaxanes, were the subject of this investigation. The necessary building blocks, alkyne-terminated axles containing two ammonium ions and azide-terminated stoppers, and azide-containing substituted macrocycles, have been synthesized and characterized. Different [3]rotaxanes were synthesized by copper-catalyzed “click” reactions between the azide stoppers and [3]pseudorotaxanes formed from the dialkyne axles and crown ethers (DB24C8). Methylation of the triazoles formed by the “click” reaction introduced a second binding site, and switching via deprotonation/protonation was investigated. In preliminary tests for the synthesis of a knotted [1]rotaxane, pseudorotaxanes were formed from azide-containing substituted macrocycles and dialkyne substituted diammonium axles, and copper-catalyzed “click” reactions were carried out. Mass spectral analyses showed successful double “click” reactions between two modified macrocycles and one axle. Whether a knotted [1]rotaxane was formed could not be determined. Full article

Today, we universally understand radicals to be chemical species with an unpaired electron. It was not always so, and this article traces the evolution of the term radical and in this journey, monitors the development of some of the great theories of organic chemistry. Full article

Pollution is increasing in the Amazon region and its real impact is still unclear. Since this region is of great interest to the global community, this study aimed to assess geochemical biomarkers and metals in sediments from three streams crossing Manaus, a Brazilian city of 2.1 million inhabitants located in the heart of the Amazon rainforest. The Mindu and Quarenta streams criss-cross the urban area of Manaus and receive domestic effluents from many heavily populated districts. In addition, the Quarenta stream is subjected to effluents from the industrial district of Manaus. The Tarumã-Açu stream is mostly covered by vegetation, although the region presents some occurrence of family farming, floating petrol station, marinas, and floating restaurants and bars. n-Alkanes were determined by Gas Chromatography with Flame Ionization Detection (GC-FID), whereas hopanes and polycyclic aromatic hydrocarbons (PAHs) were determined by Gas Chromatography coupled to Mass Spectrometry (GC-MS). The metals Ag, Cd, Cr, Co, Cu, Mn, Ni, Pb, and Zn were determined by Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) after microwave-assisted acid digestion. Concentrations of total PAHs and metals were higher in sediments from the urban streams Mindu and Quarenta because of the occurrence of more intense and diverse sources of pollution. In addition, some sediment samples from both these streams presented concentrations of fluoranthene, phenanthrene, and metals higher than the limits of low probability of adverse effects on biota established by the international guideline and by the Brazilian legislation. A similar total n-alkane concentration for sediments from all streams associated with profiles of n-alkanes with no odd/even hydrocarbon predominance suggests that biomass burning is an important source of hydrocarbons. Petroleum-derived products also represented a source for n-alkanes, as confirmed by the presence of α,β-hopanes, including an α,β-homohopane series from C₃₁ to C₃₅ with the presence of both 22S and 22R epimers. This is the first report on n-alkanes, PAHs, and hopanes in sediments from the Mindu, Quarenta, and Tarumã-Açu streams. The concentrations reported herein may be considered as baseline data in future monitoring programs of these streams. Full article

The interaction between cucurbit[7]uril (Q[7]) and a series of 4-pyrrolidinopyridinium salts bearing aliphatic substituents at the pyridinium nitrogen, namely 4-(C₄H₈N)C₅H₅NRBr, where R = H (C0), Et (C2), n-butyl (C4), n-hexyl (C6), has been studied in aqueous solution by ¹H NMR spectroscopy, electronic absorption spectroscopy, and mass spectrometry. Full article

p-^tBu-calix[4]arene (H₄TBC[4]) has proven to be an incredibly versatile ligand for the synthesis of 3d- and 3d/4f- clusters, in particular those containing mixed-valent Mn ions. These are of interest to the magnetochemist for the diversity of magnetic behaviours that can be shown, along with a huge variety of nuclearities and topologies accessible, which allow one to outline magneto-structural correlations and a quantitative understanding of their properties. This contribution reports the synthesis, analysis and magnetic properties of a Brucite-like Mn-oxo/hydroxo octanuclear fragment encapsulated within/capped by four [Mn^III-TBC[4]]⁻ moieties. A diol coligand in the reaction mixture plays a seemingly important role in determining the outcome, though it is not incorporated in the final structure. Full article

The connection of a sterically constrained 3-methyl-pyrazine ring to a N-methyl-benzimidazole unit to give the unsymmetrical α,α’-diimine ligand L5 has been programmed for the design of pseudo-octahedral spin-crossover [Fe(L5)₃]²⁺ units, the transition temperature (T_1/2) of which occurs in between those reported for related facial tris-didentate iron chromophores fitted with 3-methyl-pyridine-benzimidazole in a LaFe helicate (T_1/2 ~ 50 K) and with 5-methyl-pyrazine-benzimidazole L2 ligands (T_1/2 ~350 K). A thorough crystallographic analysis of [Fe(L5)₃](ClO₄)₂ (I), [Ni(L5)₃](ClO₄)₂ (II), [Ni(L5)₃](BF₄)₂∙H₂O (III), [Zn(L5)₃](ClO₄)₂ (IV), [Ni(L5)₃](BF₄)₂∙1.75CH₃CN (V), and [Zn(L5)₃](BF₄)₂∙1.5CH₃CN (VI) shows the selective formation of pure facial [M(L5)₃]²⁺ cations in the solvated crystals of the tetrafluoroborate salts and alternative meridional isomers in the perchlorate salts. Except for a slightly larger intra-strand interannular twist between the aromatic heterocycles in L5, the metric parameters measured in [Zn(L5)₃]²⁺ are comparable to those reported for [Zn(L2)₃]²⁺, where L2 is the related unconstrained ligand. This similitude is reinforced by comparable ligand-field strengths (∆_oct) and nephelauxetic effects (as measured by the Racah parameters B and C) extracted from the electronic absorption spectra recorded for [Ni(L5)₃]²⁺ and [Ni(L2)₃]²⁺. In this context, the strictly high-spin behavior observed for [Fe(L5)₃]²⁺ within the 5–300 K range contrasts with the close to room-temperature spin-crossover behavior of [Fe(L2)₃]²⁺ (T_1/2 = 349(5) K in acetonitrile). This can be unambiguously assigned to an intraligand arm wrestling match operating in bound L5, which prevents the contraction of the coordination sphere required for accommodating low-spin Fe^II. Since the analogous 3-methyl-pyridine ring in [Fe(L3)₃]²⁺ derivatives are sometimes compatible with spin-crossover properties, the consequences of repulsive intra-strand methyl–methyl interactions are found to be amplified in [Fe(L5)₃]²⁺ because of the much lower basicity of the 3-methyl-pyrazine ring and the resulting weaker thermodynamic compensation. The decrease of the stability constants by five orders of magnitude observed in going from [M(L2)₃]²⁺ to [M(L5)₃]²⁺ (M = Ni^II and Zn^II) is diagnostic for the operation of this effect, which had been not foreseen by the authors. Full article

Chemical processes mostly happen in fluid environments where reaction partners encounter via diffusion. The bimolecular encounters take place at a nanosecond time scale. The chemical environment (e.g., solvent molecules, (counter)ions) has a decisive influence on the reactivity as it determines the contact time between two molecules and affects the energetics. For understanding reactivity at an atomic level and at the appropriate dynamic time scale, it is crucial to combine matching experimental and theoretical data. Here, we have utilized all-atom molecular-dynamics simulations for accessing the key time scale (nanoseconds) using a QM/MM-Hamiltonian. Ion pairs consisting of a radical ion and its counterion are ideal systems to assess the theoretical predictions because they reflect dynamics at an appropriate time scale when studied by temperature-dependent EPR spectroscopy. We have investigated a diketone radical anion with its tetra-ethylammonium counterion. We have established a funnel-like transition path connecting two (equivalent) complexation sites. The agreement between the molecular-dynamics simulation and the experimental data presents a new paradigm for ion–ion interactions. This study exemplarily demonstrates the impact of the molecular environment on the topological states of reaction intermediates and how these states can be consistently elucidated through the combination of theory and experiment. We anticipate that our findings will contribute to the prediction of bimolecular transformations in the condensed phase with relevance to chemical synthesis, polymers, and biological activity. Full article

Gold complexes have been traditionally employed in medicine, and currently, some gold(I) complexes, such as auranofin, are clinically used in the treatment of rheumatoid arthritis. In the last decades, both gold(I) and gold(III) complexes with different types of ligands have gained considerable attention as potential antitumor agents, showing superior activity both in vitro and in vivo to some of the clinically used agents. The present review article summarizes the results achieved in the field of synthesis and evaluation of gold complexes with amino acids and peptides moieties for their cytotoxicity. The first section provides an overview of the gold(I) complexes with amino acids and peptides, which have shown antiproliferative activity, while the second part is focused on the activity of gold(III) complexes with these ligands. A systematic summary of the results achieved in the field of gold(I/III) complexes with amino acids and peptides could contribute to the future development of metal complexes with these biocompatible ligands as promising antitumor agents. Full article

Silver(I) is being largely studied for its antimicrobial properties. In parallel to that growing interest, some researchers are investigating the effect of this ion on eukaryotes and the mechanism of silver resistance of certain bacteria. For these studies, and more generally in biology, it is necessary to work in buffer systems that are most suitable, i.e., that interact least with silver cations. Selected buffers such as 4-(2-hydroxyethyl)-1-piperazineethane sulfonic acid (HEPES) were therefore investigated for their use in the presence of silver nitrate. Potentiometric titrations allowed to determine stability constants for the formation of (Ag(Buffer)) complexes. The obtained values were adapted to extract the apparent binding constants at physiological pH. The percentage of metal ions bound to the buffer was calculated at this pH for given concentrations of buffer and silver to realize at which extent silver was interacting with the buffer. We found that in the micromolar range, HEPES buffer is sufficiently coordinating to silver to have a non-negligible effect on the thermodynamic parameters determined for an analyte. Morpholinic buffers were more suitable as they turned out to be weaker complexing agents. We thus recommend the use of MOPS for studies of physiological pH. Full article

Structurally divergent molecules containing bulky substituents tend to produce porous materials via frustrated packing. Two rigid tetrahedral cores, tetraphenylmethane and 1,3,5,7-tetraphenyladamantane, grafted peripherally with four (trimethylsilyl)ethynyl moieties, were found to have only isolated voids in their crystal structures. Hence, they were modified into tecton-like entities, tetrakis(4-(iodoethynyl)phenyl)methane [I₄TEPM] and 1,3,5,7-tetrakis(4-(iodoethynyl)phenyl)adamantane [I₄TEPA], in order to deliberately use the motif-forming characteristics of iodoethynyl units to enhance crystal porosity. I₄TEPM not only holds increased free volume compared to its precursor, but also forms one-dimensional channels. Furthermore, it readily co-crystallizes with Lewis basic solvents to afford two-component porous crystals. Full article