Search

The presence of amino acids on the prebiotic Earth, either stemming from endogenous chemical routes or delivered by meteorites, is consensually accepted. Prebiotically plausible pathways to peptides from inactivated amino acids are still unclear as most oligomerization approaches rely on thermodynamically disfavored reactions in solution. Now, a combination of prebiotically plausible minerals and mechanochemical activation enables the oligomerization of glycine at ambient temperature in the absence of water. Raising the reaction temperature increases the degree of oligomerization concomitantly with the formation of a commonly unwanted cyclic glycine dimer (DKP). However, DKP is a productive intermediate in the mechanochemical oligomerization of glycine. The findings of this research show that mechanochemical peptide bond formation is a dynamic process that provides alternative routes towards oligopeptides and establishes new synthetic approaches for prebiotic chemistry., (© 2021 Wiley-VCH GmbH.)

The role of the Cl - anion as a templating agent for the synthesis of cyclopeptides was assessed through the preparation of three new homocyclolysines and other six cyclic peptides by head-to-tail lactamization. Isolated yields of products obtained by chloride-templating approach were considerably higher than those gained by a cation-promoted procedure, whereby, in some cases, only the anion-assisted synthesis yielded the desired cyclopeptides.

Preventing bacterial attachment to surfaces is the most efficient approach to controlling biofilm proliferation. The aim of this study was to compare anti-adhesion potentials of 5 and 50 mmol/L polyelectrolyte multilayers of poly(allylamine hydrochloride)/poly(sodium 4-styrenesulfonate), poly(4-vinyl-N-ethylpyridinium bromide)/ poly(sodium 4-styrenesulfonate), and poly(4-vinyl-N-isobutylpyridinium bromide)/poly(sodium 4-styrenesulfonate) against Escherichia coli. Glass surface was covered with five polyelectrolyte layers and exposed to bacterial suspensions. Poly(4-vinyl-N-ethylpyridinium bromide)/poly(sodium 4-styrenesulfonate) was the most effective against bacterial adhesion, having reduced it by 60 %, followed by poly(4-vinyl-N-isobutylpyridinium bromide)/poly(sodium 4- styrenesulfonate) (47 %), and poly(allylamine hydrochloride)/poly(sodium 4-styrenesulfonate) (38 %). Polyelectrolyte multilayers with quaternary amine groups have a significant anti-adhesion potential and could find their place in coatings for food, pharmaceutical, and medical industry.

Tetratopic porphyrin-based metal-organic frameworks (MOFs) represent a particularly interesting subclass of zirconium MOFs due to the occurrence of several divergent topologies. Control over the target topology is a demanding task, and reports often show products containing phase contamination. We demonstrate how mechanochemistry can be exploited for controlling the polymorphism in 12-coordinated porphyrinic zirconium MOFs, obtaining pure hexagonal PCN-223 and cubic MOF-525 phases in 20-60 min of milling. The reactions are mainly governed by the milling additives and the zirconium precursor. In situ monitoring by synchrotron powder X-ray diffraction revealed that specific reaction conditions resulted in the formation of MOF-525 as an intermediate, which rapidly converted to PCN-223 upon milling. Electron spin resonance measurements revealed significant differences between the spectra of paramagnetic centers in two polymorphs, showing a potential of polymorphic Zr-MOFs as tunable supports in spintronics applications.

A series of aromatic bis-urea derivatives was prepared and their proton dissociation, as well as anion binding properties in DMSO were investigated. To this end, UV/Vis and 1 H NMR spectroscopies and computational methods were employed. The synthesized molecules differed in the relative position of the urea moieties (ortho- and meta-derivatives) and in the functional groups (-H, -CH 3 , -OCH 3 , -NO 2 ) in the para-position of the pendant phenyl groups. Remarkably high acidities of the compounds (logK 1 H ≈14), were ascribed primarily to the stabilizing effect of the aromatic subunits. Quantum chemical calculations corroborated the conclusions drawn from experimental data and provided information from the structural point of view. Knowledge regarding protonation properties proved to be essential for reliable quantitative determination of anion binding affinities. Studied receptors were selective for acetate and dihydrogen phosphate among several anions. Formation of their complexes of 1:1 and 1:2 (ligand/anion) stoichiometries was quantitatively characterized. Proton transfer was taken into account in the course of data analysis, which was especially important in the case of AcO - . ortho-Receptors were proven to be more efficient acetate binders, achieving coordination with all four NH groups. The meta-analogues preferred dihydrogen phosphate, which acted as both hydrogen bond donor and acceptor. Cooperative binding was detected in the case of 1:2 H 2 PO 4 - complexes, which was assigned to formation of interanionic hydrogen bonds., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Cation complexation in water presents a unique challenge in calixarene chemistry, mostly due to the fact that a vast majority of calixarene-based cation receptors is not soluble in water or their solubility has been achieved by introducing functionalities capable of (de)protonation. Such an approach inevitably involves the presence of counterions which compete with target cations for the calixarene binding site, and also rather often requires the use of ion-containing buffer solutions in order to control the pH. Herein we devised a new strategy towards the solution of this problem, based on introducing carbohydrate units at the lower or upper rim of calix[4]arenes which comprise efficient cation binding sites. In this context, we prepared neutral, water-soluble receptors with secondary or tertiary amide coordinating groups, and studied their complexation with alkali metal cations in aqueous and methanol (for the comparison purpose) solutions. Complexation thermodynamics was quantitatively characterized by UV spectrometry and isothermal titration calorimetry, revealing that one of the prepared tertiary amide derivatives is capable of remarkably efficient (log K ≈ 5) and selective binding of sodium cations among alkali metal cations in water. Given the ease of the synthetic procedure used, and thus the variety of accessible analogues, this study can serve as a platform for the development of reagents for diverse purposes in aqueous media.

The medium effect on the complexation of alkali metal cations with a calix[4]arene ketone derivative (L) was systematically examined in methanol, ethanol, N-methylformamide, N,N-dimethylformamide, dimethyl sulfoxide, and acetonitrile. In all solvents the binding of Na + cation by L was rather efficient, whereas the complexation of other alkali metal cations was observed only in methanol and acetonitrile. Complexation reactions were enthalpically controlled, while ligand dissolution was endothermic in all cases. A notable influence of the solvent on NaL + complex stability could be mainly attributed to the differences in complexation entropies. The higher NaL + stability in comparison to complexes with other alkali metal cations in acetonitrile was predominantly due to a more favorable complexation enthalpy. The 1 H NMR investigations revealed a relatively low affinity of the calixarene sodium complex for inclusion of the solvent molecule in the calixarene hydrophobic cavity, with the exception of acetonitrile. Differences in complex stabilities in the explored solvents, apart from N,N-dimethylformamide and acetonitrile, could be mostly explained by taking into account solely the cation and complex solvation. A considerable solvent effect on the complexation equilibria was proven to be due to an interesting interplay between the transfer enthalpies and entropies of the reactants and the complexes formed.

The complexation of alkali metal cations by lower rim N,N-dihexylacetamide (L1) and newly synthesized N-hexyl-N-methylacetamide (L2) calix[4]arene tertiary-amide derivatives was thoroughly studied at 25 °C in acetonitrile (MeCN), benzonitrile (PhCN), and methanol (MeOH) by means of direct and competitive microcalorimetric titrations, and UV and 1 H NMR spectroscopies. In addition, by measuring the ligands' solubilities, the solution (transfer) Gibbs energies of the ligands and their alkali metal complexes were obtained. The inclusion of solvent molecules in the free and complexed calixarene hydrophobic cavities was also investigated. Computational (classical molecular dynamics) investigations of the studied systems were also carried out. The obtained results were compared with those previously obtained by studying the complexation ability of an N-hexylacetamidecalix[4]arene secondary-amide derivative (L3). The stability constants of 1 : 1 complexes were determined in all solvents used (the values obtained by different methods being in excellent agreement), as were the corresponding complexation enthalpies and entropies. Almost all of the examined reactions were enthalpically controlled. The most striking exceptions were reactions of Li + with both ligands in methanol, for which the entropic contribution to the reaction Gibbs energy was substantial due the entropically favourable desolvation of the smallest lithium cation. The thermodynamic stabilities of the complexes were quite solvent dependent (the stability decreased in the solvent order: MeCN > PhCN ≫ MeOH), which could be accounted for by considering the differences in the solvation of the ligand and free and complexed alkali metal cations in the solvents used. Comparison of the stability constants of the ligand L1 and L2 complexes clearly revealed that the higher electron-donating ability of the hexyl with respect to the methyl group is of considerable importance in determining the equilibria of the complexation reactions. Additionally, the quite strong influence of intramolecular hydrogen bond formation in compound L3 (not present in ligands L1 and L2) and that of the inclusion of solvent molecules in the calixarene hydrophobic cone were shown to be of great importance in determining the thermodynamic stability of the calixarene-cation complexes. The experimental results were fully supported by those obtained by MD simulations.

Derivatives of dehydroacetic acid comprising amide or urea subunits have been synthesized and their anion-binding properties investigated. Among a series of halides and oxyanions, the studied compounds selectively bind acetate and dihydrogen phosphate in acetonitrile and dimethyl sulfoxide. The corresponding complexation processes were characterized by means of 1 H NMR titrations, which revealed a 1:1 complex stoichiometry in most cases, with the exception of dihydrogen phosphate, which formed 2:1 (anion/ligand) complexes in acetonitrile. The complex stability constants were determined and are discussed with respect to the structural properties of the receptors, the hydrogen-bond-forming potential of the anions, and the characteristics of the solvents used. Based on the spectroscopic data and results of Monte Carlo simulations, the amide or urea groups were affirmed as the primary binding sites in all cases. The results of the computational methods indicate that an array of both inter- and intramolecular hydrogen bonds can form in the studied systems, and these were shown to play an important role in defining the overall stability of the complexes. Solubility measurements were carried out in both solvents and the thermodynamics of transfer from acetonitrile to dimethyl sulfoxide were characterized on a quantitative level. This has afforded a detailed insight into the impact of the medium on the complexation reactions., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Three m-substituted phenol derivatives, each with a labile benzylic alcohol group and bearing either protoadamantyl 4, homoadamantyl 5, or a cyclohexyl group 6, were synthesized and their thermal acid-catalyzed and photochemical solvolytic reactivity studied, using preparative irradiations, fluorescence measurements, nanosecond laser flash photolysis, and quantum chemical calculations. The choice of m-hydroxy-substitution was driven by the potential for these phenolic systems to generate m-quinone methides on photolysis, which could ultimately drive the excited-state pathway, as opposed to forming simple benzylic carbocations in the corresponding thermal route. Indeed, thermal acid-catalyzed reactions gave the corresponding cations, which undergo rearrangement and elimination from 4, only elimination from 5, and substitution and elimination from 6. On the other hand, upon photoexcitation of 4-6 to S1 in a polar protic solvent, proton dissociation from the phenol, coupled with elimination of the benzylic OH (as hydroxide ion) gave zwitterions (formal m-quinone methides). The zwitterions exhibit reactivity different from the corresponding cations due to a difference in charge distribution, as shown by DFT calculations. Thus, protoadamantyl zwitterion has a less nonclassical character than the corresponding cation, so it does not undergo 1,2-shift of the carbon atom, as observed in the acid-catalyzed reaction.

In situ Raman spectroscopy was employed to study the course of a mechanochemical nucleophilic substitution on a carbonyl group. We describe evidence of base catalysis, akin to catalysis in solution, achieved by liquid-assisted grinding.

[4-(2-Pyrrolyl)phenyl]pyridines 2-4 were synthesized and their photophysical properties and reactivity in phototautomerization reactions investigated by fluorescence spectroscopy and laser flash photolysis (LFP). The pKa for the protonation of the pyridine nitrogen in 2-4 was determined by UV-vis and fluorescence titration (pKa = 5.5 for 4). On excitation in polar protic solvents, 2-4 populate charge-transfer states leading to an enhanced basicity of the pyridine (pKa* ≈ 12) and enhanced acidity of pyrrole (pKa* ≈ 8-9) enabling excited-state proton transfer (ESPT). ESPT gives rise to phototautomers and significantly quenches the fluorescence of 2-4. Phototautomers 2-T and 4-T were detected by LFP with strong transient absorption maxima at 390 nm. Phototautomers 2-T and 4-T decayed by competing uni- and bimolecular reactions. However, at pH 11 the decay of 4-T followed exponential kinetics with a rate constant of 4.2 × 10(6) s(-1). The pyridinium salt 4H(+) forms a stable complex with cucurbit[7]uril (CB[7]) with 1:1 stoichiometry (β11 = (1.0 ± 0.2) × 10(5) M(-1), [Na(+)] = 39 mM). Complexation to CB[7] increased the pKa for 4H(+) (pKa = 6.9) and changed its photochemical reactivity. Homolytic cleavage of the pyrrole NH leads to the formation of an N-radical because of the decreased acidity of the pyrrole in the inclusion complex.

Complexation of dihydrogen phosphate by novel thiourea and urea receptors in acetonitrile and dimethyl sulfoxide was studied in detail by an integrated approach by using several methods (isothermal titration calorimetry, ESI-MS, and (1)H NMR and UV spectroscopy). Thermodynamic investigations into H2PO4(-) dimerisation, which is a process that has been frequently recognised, but rarely quantitatively described, were carried out as well. The corresponding equilibrium was taken into account in the anion-binding studies, which enabled reliable determination of the complexation thermodynamic quantities. In both solvents the thiourea derivatives exhibited considerably higher binding affinities with respect to those containing the urea moiety. In acetonitrile, 1:1 and 2:1 (anion/receptor) complexes formed, whereas in dimethyl sulfoxide only the significantly less stable complexes of 1:1 stoichiometry were detected. The solvent effects on the thermodynamic parameters of dihydrogen phosphate dimerisation and complexation reactions are discussed., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Three libraries of adamantane derivatives were synthesized and evaluated for antiviral and antiproliferative activities against a broad variety of DNA and RNA viruses. Whereas none of the compounds exhibit antiviral activity at subtoxic concentrations, antiproliferative activity was found against murine leukemia cells (L1210), human T-lymphocyte cells (CEM), and cervix carcinoma cells (HeLa) for 4, 8, and 10., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A series of (1-adamantyl)phthalimides, 1-4, and (2-adamantyl)phthalimides, 5-8, characterized by different chain length between the adamantyl and the phthalimide moiety were synthesized, as well as 1- and 2-adamantylphthalimides substituted by nitro 9, 10, and amino group 11, 12, and phthalimides bearing homoadamantyl 13 and protoadamantyl substituent 14 and 15. The compounds were tested for antiproliferative activity in vitro on a series of five human cancer lines: MCF-7 (breast carcinoma), SW 620 (colon carcinoma), HCT 116 (colon carcinoma), MOLT-4 (acute lymphoblastic leukemia), H 460 (lung carcinoma), and a non-tumor cell line HaCaT (human keratinocytes). All compounds except nitro derivatives 9 and 10 exhibited antiproliferative activity. The activity was generally better in the 2-adamantyl series 5-8 and in the compounds having the longest alkyl spacers as in 4 and 8, or with an amino group as in 9 and 10. The most active compounds with the propylene spacer 4 and 8 showed the highest selectivity toward tumor cells. The activity was found to be due to a delay in the progress through the cell cycle at G1/S phase., (© 2011 John Wiley & Sons A/S.)

In aqueous media, photochemical excitation to S(1) of 3-phenylphenols 4-8 leads to deprotonation of the phenol OH, coupled with protonation of the benzyl alcohol and overall dehydration that delivers zwitterions 17-21. The zwitterions react with nucleophiles (CH(3)OH, CF(3)CH(2)OH and ethanolamine) converting them in high quantum yields to the corresponding adducts and photosolvolysis products (for photomethanolysis Φ~0.1-0.5). Zwitterions 20 and 21 were characterized by laser flash photolysis in CH(3)CN-H(2)O (τ~7.5 and 25 μs, respectively) and the associated quenching rate constants with nucleophiles azide and ethanolamine determined. In vitro studies of antiproliferative activity of the photochemicaly generated QMs and zwitterions formed from 2-, 3- and 4-phenylphenols were carried out on three human cancer cell lines HCT 116 (colon), MCF-7 (breast), and H 460 (lung). Irradiation of cells incubated with 3, 6, and 26 showed enhanced antiproliferative activity compared to the cells that were not irradiated., (This journal is © The Royal Society of Chemistry and Owner Societies 2012)

In aqueous media, photochemical excitation (S(1)) of hydroxyadamantyl, diphenylhydroxymethyl, and hydroxypropyl derivatives of 4-phenylphenol 5-9 leads to solvent-assisted deprotonation of the phenol OH, and protonation of the benzyl alcohol coupled with dehydration, that delivers quinone methides (QMs) 14-18. The QMs react with CH(3)OH converting them in high quantum yields to the photosolvolysis products (overall Φ∼ 0.1-0.5). QMs were characterized by laser flash photolysis in CH(3)CN-H(2)O and TFE. In TFE, the zwitterionic QM 15 has a lifetime of 250 ns, whereas para QMs 16 and 17 have lifetimes of 500 μs and 1.1 s, respectively. Introduction of the steric hindrance to the parent QM structure (with the adamantyl moiety), or additional stabilization by two phenyl rings, results in an increase of QM lifetimes and selectivity in the reactions with nucleophiles. In vitro studies of the antiproliferative activity of photochemically generated QMs 15-17 were carried out on one human cancer cell line. Irradiation of cells incubated with 7 showed enhanced antiproliferative activity compared to cells that were not irradiated, in accordance with the activity being due to the formation of QM 16.

N-(4-homoadamantyl)phthalimide (5) on excitation and population of the triplet excited state underwent intramolecular H-abstractions and gave products 6 and 7. The major product, exo-alcohol 6 was a result of the regioselective δ H-abstraction and the stereoselective cyclization of the 1,5-biradical. Minor products 7 were formed by photoinduced γ H-abstractions, followed by ring closure to azetidinols and ring enlargement to azepinediones. The observed selectivity to exo-alcohol 6 was explained by the conformation of 5 and the best orientation and the availability of the δ-H for the abstraction.

Four different combinations of 9644Ru and 9640Zr nuclei, both as projectile and target, were investigated at the same bombarding energy of 400A MeV using a 4pi detector. The degree of isospin mixing between projectile and target nucleons is mapped across a large portion of the phase space using two different isospin-tracer observables, the number of measured protons and the tritium to 3He yield ratio. The experimental results show that the global equilibrium is not reached even in the most central collisions. Quantitative measures of stopping and mixing are extracted from the data. They are found to exhibit a quite strong sensitivity to the in-medium ( n,n) cross section used in microscopic transport calculations.