Armeria maritima is a halophyte exhibiting a strong tolerance to heavy metals. It grows on zinc-lead waste heaps. This study aimed to determine the role of salt glands in the removal of lead (Pb) from plants and to trace the path of lead from the shoots to the salt glands on the surface of leaves. Mechanisms allowing high tolerance to lead in A. maritima were also evaluated. These examinations were conducted on a lead-tolerant population and a lead-sensitive plant population. The plants were treated with Pb(NO3)2 and the path of lead was traced from the roots to the leaves. The lead-tolerant population transported twice as much lead as the sensitive population. The action of the salt glands resulted in 40% of the leaf lead content in the lead-tolerant population being expelled onto the surface of the leaves. These features indicate the high phytoremediation capabilities of these halophyte plants. The excretion of multi-ionic solutes by the salt glands results in the appearance of tiny crystals on the surface of the leaves. In this publication, for the first time, an attempt was made to determine what chemical compounds build up these crystals and to determine their crystal structure. Solving this problem was possible through the usage of single-crystal X-ray structural analysis.
Four isomeric di-6-oxoverdazyl diradicals connected at their N(1) or C(3) positions with either 1,3- or 1,4-phenylene linkers were obtained and characterized by spectroscopic, electrochemical, magnetic, and structural methods. These results were compared to those for the corresponding 6-oxoverdazyl monoradicals. UV-vis spectroscopy demonstrated that only the N(1)-connected para-through-benzene diradical has a distinct spectrum with significant bathochromic and hypsochromic shifts relative to the remaining species. Electrochemical analysis revealed two one-electron reduction processes in all diradiacals, while only the N(1)-connected para-through-benzene diradical exhibits two one-electron oxidation processes separated by 0.10 V. Variable temperature EPR measurements in polystyrene solid solutions gave negative mean exchange interaction energies J for all diradicals, suggesting the dominance of conformers with significant intramolecular antiferromagnetic interactions for the meta-through-benzene isomers. DFT calculations predict a small preference for the triplet state with the ΔES-T of about 0.25 kcal mol-1 for both meta-through-benzene connected diradicals.
Applications of 9-aminoacridine (9aa) and its derivatives span fields such as chemistry, biology, and medicine, including anticancer and antimicrobial activities. Protonation of such molecules can alter their bioavailability as weakly basic drugs like aminoacridines exhibit reduced solubility at high pH levels potentially limiting their effectiveness in patients with elevated gastric pH. In this study, we analyse the influence of protonation on the electronic characteristics of the molecular organic crystals of 9-aminoacridine. The application of quantum crystallography, including aspherical atom refinement, has enriched the depiction of electron density in the studied systems and non-covalent interactions, providing more details than previous studies. Our experimental results, combined with a topological analysis of the electron density and its Laplacian, provided detailed descriptions of how protonation changes the electron density distribution around the amine group and water molecule, concurrently decreasing the electron density at bond critical points of N/O-H bonds. Protonation also alters the molecular architecture of the systems under investigation. This is reflected in different proportions of the Nâ¯H and Oâ¯H intermolecular contacts for the neutral and protonated forms. Periodic DFT calculations of the cohesive energies of the crystal lattice, as well as computed interaction energies between molecules in the crystal, confirm that protonation stabilises the crystal structure due to a positive synergy between strong halogen and hydrogen bonds. Our findings highlight the potential of quantum crystallography in predicting crystal structure properties and point to its possible applications in developing new formulations for poorly soluble drugs.
Discovery of a halogen-bonded ternary cocrystal of 1,3,5-trifluoro-2,4,6-triiodobenzene with pyrazine and triphenylphosphine sulfide has revealed a complex landscape of multicomponent phases, all achievable by mechanochemical interconversion. The observed solid-state reaction pathways were explained by periodic density-functional calculations and comprehensive intermolecular interaction analysis, supported by dissolution calorimetry measurements.
Cyclic dipeptides with two intramolecular peptide bonds forming a six-membered 2,5-diketopiperazine ring are gaining significant attention due to their biological and chemical properties. Small changes in the local geometry of such molecules (from cis to trans) can lead to significant structural differences. This work presents the results of a study of cyclo(l-Cys-d-Cys), a dipeptide comprising two cysteine molecules in opposite chiral configurations, with the functional groups situated at both sides of the diketopiperazine ring. X-ray diffraction (XRD) experiment revealed that the molecule crystallises in the P-1 space group, which includes the centre of inversion. The IR and Raman vibrational spectra of the molecule were acquired and interpreted in terms of the potential energy distribution (PED) according to the results of density functional theory (DFT) calculations. The DFT-assisted analysis of energy frameworks for the hydrogen bond network within molecular crystals was performed to support the interpretation of X-ray structural data. The optimisation of the computational model based on three-molecule geometry sections from the crystallographic structure, selected to appropriately reflect the intermolecular interactions responsible for the formation of 1D molecular tapes in cyclo(l-Cys-d-Cys) crystal, allowed for better correspondence between theoretical and experimental vibrational spectra. This work can be considered the first complete structural characterisation of cyclo(l-Cys-d-Cys), complemented via vibrational spectroscopy results with full band assignment aided with the use of the DFT method.
The application of Hirshfeld atom refinement (HAR) fragmentation is demonstrated for the refinement of metal-organic framework (MOF) crystal structures. The presented method enables anisotropic refinement of imidazolate hydrogen atoms, as well as complex analysis of solvent disorder within MOF pores. The data used were derived from standard resolution in-house single crystal X-ray diffraction measurements, demonstrating that high quality structural analysis of MOFs no longer requires access to neutron or synchrotron facilities.
Hydrogen , Metal-Organic Frameworks , X-Ray Diffraction , Hydrogen/chemistry , Crystallography, X-Ray , Synchrotrons
A Cu(II)-salen complex encapsulated in MWW-framework as an efficient chiral organocatalyst was developed for the synthesis of 3,4-dihydropyrimidin-2-(1H)-one (DHPMs) derivatives via an asymmetric pathway. In order to confirm its structural properties, single-crystal X-ray diffraction, powder XRD, BET, XPS, FE-SEM, EDX, UV-Vis, and FTIR spectra were used. Using computer-assisted DFT calculations, the Cu(II)-salen complex has been fine-tuned to fit into the pocket of the porous MWW support while keeping its chirality. This organocatalyst was shown to be a potent catalyst for the formation of the desired DHPMs product under short reaction times. Furthermore, this green protocol allows rapid and simple isolation of active MWW-trapped Cu(II)-salen scaffolds and its reusability in at least five consecutive runs without losing much of its activity.
The nature and strength of interactions for an anti-HIV drug, Lamivudine, were studied in a pure crystal form of the drug and the ligand-receptor complexes. High-resolution single-crystal X-ray diffraction studies of the tetragonal polymorph allowed the drug's experimental charge density distribution in the solid state to be obtained. The QM/MM calculations were performed for a simplified model of the Lamivudine complex with deoxycytidine kinase (two complexes with different binding modes) to reconstruct the theoretical charge density distribution. The peculiarities of intramolecular interactions were compared with previously reported data for an isolated molecule. Intermolecular interactions were revealed within the quantum theory of 'Atoms in Molecules', and their contributions to the total crystal energy or ligand-receptor binding energy were evaluated. It was demonstrated that the crystal field effect weakened the intramolecular interactions. Overall, the energies of intermolecular interactions in ligand-receptor complexes (320.1-394.8 kJ/mol) were higher than the energies of interactions in the crystal (276.9 kJ/mol) due to the larger number of hydrophilic interactions. In contrast, the sum of the energies of hydrophobic interactions was found to be unchanged. It was demonstrated by means of the Voronoi tessellation that molecular volume remained constant for different molecular conformations (250(13) Å3) and increased up to 399 Å3 and 521(30) Å3 for the Lamivudine phosphate and triphosphate.
Tolerance to heavy metals in plants is a model process used to study adaptations to extremely unfavorable environments. One species capable of colonizing areas with high contents of heavy metals is Armeria maritima (Mill.) Wild. A. maritima plants growing in metalliferous areas differ in their morphological features and tolerance levels to heavy metals compared to individuals of the same species growing in non-metalliferous areas. The A. maritima adaptations to heavy metals occur at the organismal, tissue, and cellular levels (e.g., the retention of metals in roots, enrichment of the oldest leaves with metals, accumulation of metals in trichomes, and excretion of metals by salt glands of leaf epidermis). This species also undergoes physiological and biochemical adaptations (e.g., the accumulation of metals in vacuoles of the root's tannic cells and secretion of such compounds as glutathione, organic acids, or HSP17). This work reviews the current knowledge on A. maritima adaptations to heavy metals occurring in zinc-lead waste heaps and the species' genetic variation from exposure to such habitats. A. maritima is an excellent example of microevolution processes in plants inhabiting anthropogenically changed areas.
Adaptation, Physiological , Metals, Heavy , Plumbaginaceae , Soil Pollutants , Zinc , Humans , Metals, Heavy/metabolism , Plumbaginaceae/metabolism , Soil Pollutants/metabolism , Zinc/metabolism
Periodic density-functional theory (DFT) calculations were used to predict the thermodynamic stability and the likelihood of interconversion between a series of halogen-bonded cocrystals. The outcomes of mechanochemical transformations were in excellent agreement with the theoretical predictions, demonstrating the power of periodic DFT as a method for designing solid-state mechanochemical reactions prior to experimental work. Furthermore, the calculated DFT energies were compared with experimental dissolution calorimetry measurements, marking the first such benchmark for the accuracy of periodic DFT calculations in modelling transformations of halogen-bonded molecular crystals.
The first-in-class luminescent dinucleoside phosphate analogs with a [Re2(µ-Cl)2(CO)6(µ-pyridazine)] "click" linker as a replacement for the natural phosphate group are reported together with the synthesis of luminescent adenosine and thymidine derivatives having the [Re2(µ-Cl)2(CO)6(µ-pyridazine)] entity attached to positions 5' and 3', respectively. These compounds were synthesized by applying inverse-electron-demand Diels-Alder and copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition reactions in three or four steps. The obtained compounds exhibited orange emission (λPL ≈ 600 nm, ΦPL ≈ 0.10, and τ = 0.33-0.61 µs) and no toxicity (except for one nucleoside) to human HeLa cervical epithelioid and Ishikawa endometrial adenocarcinoma cancer cells in vitro. Furthermore, the compounds' ability to inhibit the growth of Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacterial strains was moderate and only observed at a high concentration of 100 µM. Confocal microscopy imaging revealed that the "dirhenium carbonyl" dinucleosides and nucleosides localized mainly in the membranous structures of HeLa cells and uniformly inside S. aureus and E. coli bacterial cells. An interesting finding was that some of the tested compounds were also found in the nuclei of HeLa cells.
Nucleosides , Pyridazines , Humans , Nucleosides/chemistry , HeLa Cells , Dinucleoside Phosphates , Phosphates , Escherichia coli , Staphylococcus aureus , Click Chemistry/methods
A new highly fluorescent zinc-organic framework [Zn2(btca)(DMSO)2]n (Zn-MOF) was prepared via in situ ligand formation by the solvothermal reaction of Zn(NO3)2·6H2O and pyromellitic dianhydride (PMDA) in DMSO solvent. During the solvothermal reaction, PMDA was gradually hydrolyzed to a pyromellitic acid, 1,2,4,5-benzene tetracarboxylic acid (H4btca), to provide a tetracarboxylic acid as a linker in the reaction medium. Single-crystal X-ray diffraction analysis exhibits a 3D porous structure with open tetragonal channels running along the crystallographic c-axis. The Zn-MOF was explored as an on-mode fluorescent sensor for tracing cimetidine in biological fluids and pharmaceutical samples in the presence of interfering species. The results show a quick response in a short time range. The characteristics of this sensor were investigated by field-emission scanning electron microscopy, dynamic light scattering, energy-dispersive X-ray analysis, powder X-ray diffraction, Fourier transform infrared and UV-vis spectroscopy as well as thermogravimetric, and elemental analyses.
Mixed-valence (MV) binuclear ferrocenyl compounds have long been studied as models for testing theories of electron transfer and in attempts to design molecular-scale electronic devices (e.g., molecular wires). In contrary to that, far less attention has been paid to MV binuclear ferrocenes as anticancer agents. Herein, we discuss the synthesis of six 1,2,3-triazole ferrocenyl compounds for combined (spectro)electrochemical, electron paramagnetic resonance (EPR), computational, and anticancer activity studies. Our synthetic approach was based on the copper-catalyzed 1,3-dipolar azide-alkyne cycloaddition reaction and enabled us to obtain in one step compounds bearing either one, two, or three ferrocenyl entities linked to the common 1,2,3-triazole core. Thus, two series of complexes were obtained, which pertain to derivatives of 3'-azido-3'-deoxythymidine (AZT) and 3-azidopropionylferrocene, respectively. Based on the experimental and theoretical data, the two mono-oxidized species corresponding to binuclear AZT and trinuclear 3-azidopropionylferrocene complexes have been categorized as class II mixed-valence according to the classification proposed by Robin and Day. Of importance is the observation that these two compounds are more active against human A549 and H1975 non-small-cell lung cancer cells than their congeners, which do not show MV characteristics. Moreover, the anticancer activity of MV species competes or surpasses, dependent on the cell line, the activity of reference anticancer drugs such as cisplatin, tamoxifen, and 5-fluorouracil. The most active from the entire series of compounds was the binuclear thymidine derivative with the lowest IC50 value of 5 ± 2 µM against lung H1975 cancer cells. The major mechanism of antiproliferative activity for the investigated MV compounds is based on reactive oxygen species generation in cancer cells. This hypothesis was substantiated by EPR spin-trapping experiments and the observation of decreased anticancer activity in the presence of N-acetyl cysteine (NAC) free-radical scavenger.
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Antineoplastic Agents/chemistry , Electronics , Humans , Metallocenes , Reactive Oxygen Species/metabolism , Triazoles/chemistry
Water splitting is a promising way to alleviate the energy crisis. In nature, water oxidation is done by a tetranuclear manganese cluster in photosystem II. Therefore, the study of water oxidation by Mn complexes is attractive in water splitting systems. In this report, a new mononuclear Mn(II) complex, MnL2 (HL = (E)-3-hydroxy-N'-(pyridin-2-ylmethylene)-2-naphthohydrazide) was prepared and characterized by spectroscopic techniques and single-crystal X-ray diffraction. Crystallographic analysis indicated that the geometry around the Mn(II) ion is distorted octahedral. The MnN4O2 coordination moiety is achieved by bounding of oxygen and two nitrogen donor atoms of two hydrazone ligands. The synthesized complex was also investigated for electrochemical water oxidation using electrochemical techniques, scanning electron microscopy, energy dispersive spectrometry, and PXRD analysis. Linear sweep voltammetry experiment showed that the modified carbon paste electrode by the complex displays high activity for water oxidation reaction with an overpotential of 565 mV at a current density of 10 mA cm-2 and Tafel slope of 105 mV dec-1 in an alkaline solution. It was found that the complex structure finally changes during the reaction and converts to Mn oxide nanoparticles which act as active catalytic species and oxidize the water.
Manganese , Water , Water/chemistry , Manganese/chemistry , Photosystem II Protein Complex/metabolism , Oxidation-Reduction , Ligands , Oxygen/chemistry
The knowledge pertaining to the chemistry and biological activity of glycol nucleic acid (GNA) components, like nucleosides and nucleotides, is still very limited. Herein we report on the preparation of the uracil nucleoside (1) and nucleotide ester GNA (2). The compounds are functionalised with a luminescent phenanthrenyl group. In DMSO, 1 and 2 are brightly fluorescent, with emission maxima at 390 nm, nanosecond decay times (0.6 and 0.75 ns, respectively), and quantum yields of ca. 0.2. In the solid phase, they show excimeric emission, with maxima at 495 nm (1) and 432 nm (2), and decay times of 3.7 ns (1) and 2.9 ns (2). The anticancer activity of the GNA components, as well as gemcitabine hydrochloride, used as a reference drug, were examined in vitro against human cancer HeLa and Ishikawa cells, as well as against normal L929 cells, using a battery of biochemical assays. Furthermore, biodistribution imaging studies were carried out in HeLa cells, with luminescence confocal microscopy, which showed that the compounds localized mainly in the lipophilic cellular compartments. Nucleoside (1) and nucleotide ester (2) features two different anticancer activity profiles. At 24 h of treatment, the nucleoside acts mainly as a toxin and induces necrosis in HeLa cells, whereas the nucleotide ester exhibits pro-apoptotic activity. At longer treatment times (72 h), the nucleoside and the reference, gemcitabine hydrochloride, featured almost identical signs of anticancer activity, such as S-phase cell cycle arrest, proliferation inhibition, and apoptosis induction. In view of this data, one can hypothesize that despite the structural differences, the newly obtained phenanthrenyl GNA nucleoside (1) and gemcitabine may share a common mechanism of anticancer activity in HeLa cancer cells. The GNA components were also examined as antiplasmodial agents against Plasmodium falciparum, in vitro. Nucleoside (1) was found to be more potent than nucleotide (2), displaying activity in the low micromolar range. Furthermore, both phenanthrene derivatives were found to display resistance indices at least 9-fold lower than chloroquine diphosphate (CQDP).
Nucleic Acids , Esters , Glycols/chemistry , HeLa Cells , Humans , Nucleic Acids/chemistry , Nucleotides , Tissue Distribution
The structural studies on two bromo-substituted derivatives of 2-deoxy-d-glucose (2-DG), namely 2-deoxy-2-bromo-d-glucose (2-BG) and 2-deoxy-2-bromo-d-mannose (2-BM) are described. 2-DG itself is an inhibitor of hexokinase, the first enzyme in the glycolysis process, playing a vital role in both cancer cell metabolism and viral replication in host cells. Because of that, 2-DG derivatives are considered as potential anti-cancer and anti-viral drugs. An X-ray quantum crystallography approach allowed us to obtain more accurate positions of hydrogen atoms by applying Hirshfeld atom refinement, providing a better description of hydrogen bonding even in the case of data from routine X-ray experiments. Obtained structures showed that the introduction of bromine at the C2 position in the pyranose ring has a minor influence on its conformation but still, it has a noticeable effect on the crystal structure. Bromine imposes the formation of a layered supramolecular landscape containing hydrogen bonds, which involves the bromine atom. Periodic DFT calculations of cohesive and interaction energies (at the B3LYP level of theory) have supported these findings and highlighted energetic changes upon bromine substitution. Based on molecular wavefunction from the refinement, we calculated the electrostatic potential, Laplacian, and ELI-D, and applied them to charge-density studies, which confirmed the geometry of hydrogen bonding and involvement of the bromine atom with these intermolecular interactions. NMR studies in the solution show that both compounds do not display significant differences in their anomeric equilibria compared to 2-DG, and the pyranose ring puckering is similar in both aqueous and solid state.
[This corrects the article DOI: 10.1039/D1RA08312K.].
Herein, a framework for the estimation of the thermodynamic properties of molecular crystals via the refinement of frequencies from density functional theory calculations against X-ray diffraction data is presented. The framework provides an efficient approach to including the contribution of acoustic modes in the thermodynamic properties. The obtained heat capacities for urea, the α- and ß-glycine polymorphs, benzoic acid, and 4'-hydroxyacetophenone are in good agreement with those from adiabatic calorimetry.
Acetophenones/chemistry , Benzoic Acid/chemistry , Density Functional Theory , Glycine/chemistry , Calorimetry , Thermodynamics , X-Ray Diffraction
The lithium complexes [(WCA-NHC)Li(toluene)] of anionic N-heterocyclic carbenes with a weakly coordinating borate moiety (WCA-NHC, WCA=B(C6 F5 )3 , NHC=IDipp=1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene) were used for the preparation of silver(I) or copper(I) WCA-NHC complexes. While the reactions in THF with AgCl or CuCl afforded anionic mono- and dicarbene complexes with solvated lithium counterions [Li(THF)n ]+ (n=3, 4), the reactions in toluene proceeded with elimination of LiCl and formation of the neutral phosphine and arene complexes [(WCA-NHC)M(PPh3 )] and [(WCA-NHC)M(η2 -toluene)] (M=Ag, Cu). The latter were used for the preparation of chlorido- and iodido-bridged heterobimetallic Ag/Ru and Cu/Ru complexes [(WCA-NHC)M(µ-X)2 Ru(PPh3 )(η6 -p-cymene)] (M=Ag, Cu, X=Cl; M=Ag, X=I). Surprisingly, these complexes resisted the elimination of CuCl, AgCl, or AgI, precluding WCA-NHC transmetalation.
The metal-free reduction of a range of phosphine(V) oxides employing oxalyl chloride as an activating agent and hexachlorodisilane as reducing reagent has been achieved under mild reaction conditions. The method was successfully applied to the reduction of industrial waste byproduct triphenylphosphine(V) oxide, closing the phosphorus cycle to cleanly regenerate triphenylphosphine(III). Mechanistic studies and quantum chemical calculations support the attack of the dissociated chloride anion of intermediated phosphonium salt at the silicon of the disilane as the rate-limiting step for deprotection. The exquisite purity of the resultant phosphine(III) ligands after the simple removal of volatiles under reduced pressure circumvents laborious purification prior to metalation and has permitted the facile formation of important transition metal catalysts.
