A study of strong halogen bonding within three series of halogen‐bonded complexes, derived from seven para‐substituted pyridine derivatives and three N‐halosuccinimides (iodo, bromo and chloro), has ...been undertaken with the aid of single‐crystal diffraction, solution complexation and computational methods. The halogen bond was compared with the hydrogen bond in an equivalent series based on succinimide. The halogen‐bond energies are in the range −60 to −20 kJ mol−1 and change regularly with pyridine basicity and the Lewis acidity of the halogen. The halogen‐bond energies correlate linearly with the product of charges on the contact atoms, which indicates a predominantly electrostatic interaction. The binding enthalpies in solution are around 19 kJ mol−1 less negative due to solvation effects. The optimised geometries of the complexes in the gas phase are comparable to those of the solid‐state structures, and the effects of the supramolecular surroundings in the latter are discussed. The bond energies for the hydrogen‐bonded series are intermediate between the halogen‐bond energies of iodine and bromine, although there are specific differences in the geometries of the halogen‐ and hydrogen‐bonded complexes.
Halogen bonding revealed! A combined computational, solution and crystallographic study of three series of halogen‐bonded, and an equivalent series of hydrogen‐bonded, complexes reveals details on halogen bonding with several halogens and halogen acceptors of different basicities, and has enabled a comparison of halogen and hydrogen bonds in identical surroundings (see figure).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In the present study, four O-substituted oximes of quinuclidin-3-one were synthesized using appropriate O-substituted hydroxylamine hydrochlorides. In order to perform these reactions in a solvent, a ...mixture of (E) and (Z) products was yielded. Using mechanochemical and microwave synthesis, we then obtained pure (E) oximes. In almost all cases, the conversion to oxime ethers was completed. Reactions were monitored by ATR spectroscopy and the ratios of (E) and (Z) oxime ethers were deduced from 1H NMR data. Several reactions were very rapid (1 min) with 100% conversion and stereospecificity. To investigate the reaction mechanisms, full conformational analyses of the reaction intermediates were performed and the lowest energy conformers were determined. These conformers differed in spatial arrangement around the nitrogen atom of the amino group and were in the correct orientation for reactions to occur. Calculated standard Gibbs energies of the formation were in agreement with the experimentally obtained ratios of (E) and (Z) isomers. This work shows alternatives to the classical synthesis of O-substituted oxime ether precursors and highlights the fast reaction rate and stereoselectivity of microwave synthesis as well as the “green” aspects of mechanochemistry.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This paper describes the synthesis and anticholinesterase potency of Cinchona-based alkaloids; ten quaternary derivatives of cinchonines and their corresponding pseudo-enantiomeric cinchonidines. The ...quaternization of quinuclidine moiety of each compound was carried out with groups diverse in their size: methyl, benzyl and differently meta- and para-substituted benzyl groups. All of the prepared compounds reversibly inhibited human butyrylcholinesterase and acetylcholinesterase with Ki constants within nanomolar to micromolar range. Five cinchonidine derivatives displayed 95-510 times higher inhibition selectivity to butyrylcholinesterase over acetylcholinesterase and four were potent butyrylcholinesterase inhibitors with Ki constants up to 100 nM, of which N-para-bromobenzyl cinchonidinium bromide can be considered a lead for further modifications and optimizations for possible use in the treatment of neurodegenerative diseases.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The propensity of 4-hydroxybenzhydrazone-related ligands derived from 3-methoxysalicylaldehyde (H
L
), 4-methoxysalicylaldehyde (H
L
), and salicylaldehyde (H
L
) to act as chelating and/or bridging ...ligands in Ni(II) complexes was investigated. Three clusters of different nuclearities, Ni
(L
)
(OAc)
(MeOH)
∙2MeOH∙MeCN (
∙2MeOH∙MeCN), Ni
(HL
)(L
)(OAc)(MeOH)
∙4.7MeOH (
∙4.7MeOH), and Ni
(HL
)
(L
)
(OAc)
∙4MeOH·0.63H
O·0.5MeCN·HOAc (
∙4MeOH·0.63H
O·0.5MeCN·HOAc), were prepared from Ni(OAc)
∙4H
O and the corresponding ligand in the presence of Et
N. The hydrazones in these acetato- and phenoxido-bridged clusters acted as singly or doubly deprotonated ligands. When pyridine was used, mononuclear complexes with the square-planar geometry seemed to be favoured, as found for complexes Ni(L
)(py) (
), Ni(L
)(py) (
) and Ni(L
)(py) (
). Ligand substituent effects and the stability of square-planar complexes were investigated and quantified by extensive quantum chemical analysis. Obtained results showed that standard Gibbs energies of binding were lower for square-planar than for octahedral complexes. Starting from MoO
(L)(EtOH) complexes as precursors and applying the metal-exchange procedure, the mononuclear complexes Ni(HL
)
∙MeOH (
∙MeOH) and Ni(HL
)∙2MeOH (
∙2MeOH) and hybrid organic-inorganic compound Ni
(HL
)
(CH
OH)
Mo
O
(OCH
)
(
) were achieved. The octahedral complexes Ni(HL)
(
-
) can also be obtained by the direct synthesis from Ni(Oac)
∙4H
O and the appropriate ligand under specific reaction conditions. Crystal and molecular structures of
∙2MeOH∙MeCN,
∙4.7MeOH,
∙4MeOH∙0.63H
O∙0.5MeCN∙HOAc,
,
,
∙2MeOH, and
were determined by the single-crystal X-ray diffraction method.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Developing new antibiotics is currently very important since antibiotic resistance is one of the biggest problems of global health today. In the search for a new class of potential antimicrobial ...agents, ten new compounds were designed and synthesized based on the quinuclidinium heterocyclic core and the oxime functional group. The antimicrobial activity was assessed against a panel of representative gram-positive and gram-negative bacteria. All compounds demonstrated potent activity against the tested microorganisms, with the minimum inhibitory concentration (MIC) values ranging from 0.25 to 256.00 μg/mL. Among the tested compounds, two quaternary compounds,
-
-chlorobenzyl and
-
-bromobenzyl quinuclidinium oximes, displayed the most potent and broad-spectrum activity against both gram-positive and gram-negative bacterial strains (MIC values from 0.25 to 4.00 μg/mL), with the lowest value for the important multidrug resistant gram-negative pathogen
. In the case of
, activity of those compounds are 256-fold and 16-fold better than gentamicin, respectively. MTT assays showed that compounds are nontoxic for human cell lines. Multi-way analysis was used to separately reduce dimensionality of quantum chemical data and biological activity data to obtain a regression model and the required parameters for the enhancement of biological activity.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A series of 46 Cinchona alkaloid derivatives that differ in positions of fluorine atom(s) in the molecule were synthesized and tested as human acetylcholinesterase (AChE) and butyrylcholinesterase ...(BChE) inhibitors. All tested compounds reversibly inhibited AChE and BChE in the nanomolar to micromolar range; for AChE, the determined enzyme-inhibitor dissociation constants (Ki) ranged from 3.9–80 µM, and 0.075–19 µM for BChE. The most potent AChE inhibitor was N-(para-fluorobenzyl)cinchoninium bromide, while N-(meta-fluorobenzyl)cinchonidinium bromide was the most potent BChE inhibitor with Ki constant in the nanomolar range. Generally, compounds were non-selective or BChE selective cholinesterase inhibitors, where N-(meta-fluorobenzyl)cinchonidinium bromide was the most selective showing 533 times higher preference for BChE. In silico study revealed that twenty-six compounds should be able to cross the blood-brain barrier by passive transport. An extensive machine learning procedure was utilized for the creation of multivariate linear regression models of AChE and BChE inhibition. The best possible models with predicted R2 (CD-derivatives) of 0.9932 and R2(CN-derivatives) of 0.9879 were calculated and cross-validated. From these data, a smart guided search for new potential leads can be performed. These results pointed out that quaternary Cinchona alkaloids are the promising structural base for further development as selective BChE inhibitors which can be used in the central nervous system.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•Geographical origin of wine is the major authenticity feature and quality indicator.•NMR and ICP-MS used for deep learning provides a novel wine classification model.•The model is particularly ...useful in cases where the number of samples is limited.•It has potential for quality and authenticity control of wine.
An approach that combines NMR spectroscopy and inductively coupled plasma mass spectrometry (ICP-MS) and advanced tensor decomposition algorithms with state-of-the-art deep learning procedures was applied for the classification of Croatian continental sparkling wines by their geographical origin. It has been demonstrated that complex high-dimensional NMR or ICP-MS data cannot be classified by higher-order tensor decomposition alone. Extension of the procedure by deep reinforcement learning resulted in an exquisite neural network predictive model for the classification of sparkling wines according to their geographical origin. A network trained on half of the sample set was able to classify even 94% of all samples. The model can particularly be useful in cases where the number of samples is limited and when simpler statistical methods fail to produce reliable data. The model can further be exploited for the identification and differentiation of sparkling wines including a high potential for authenticity or quality control.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Solution state structures of enamine derivatives determined.•Enaminones adopt localised keto-amine tautomeric form.•Quantum chemical calculations corroborate NMR and UV data.•Intra- and ...inter-molecular hydrogen bonds exist in solution state.
The structure and hydrogen bonding in solution of acetylacetone and benzoylacetone derived enaminone derivatives, 1a–1d and 2a–2d, have been studied by a combination of experimental (NMR and UV spectroscopies) and theoretical (PM6 and DFT) methods. It has been shown that all studied compounds predominantly existed in the localised keto-amine tautomeric form in solution as found also in the solid state. Significant line-broadening and down-field chemical shifts of NH and OH protons have strongly indicated that both groups formed hydrogen bonds, which has further been supported by quantum chemical calculations. Temperature and concentration dependent NMR measurements have pointed towards the fact that NH protons are engaged in strong intramolecular hydrogen bonds of the NH⋯OC type in both solvents. On the other hand, OH protons are involved in weaker intermolecular hydrogen bonding with solvent molecules in DMSO, while in chloroform intermolecular interactions between two molecules dominate. The results presented in this paper can be used for better understanding and further exploiting properties these ligands possess, especially their bioactivity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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