Next Article in Journal
Experimental and Theoretical Investigation of the Elastic Properties of HfV2O7
Previous Article in Journal
Dielectric Response of ZnTe–Ti/Al Schottky Junctions with CdTe Quantum Dots Studied by Impedance Spectroscopy
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Crystals
Volume 10
Issue 3
10.3390/cryst10030171
crystals-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

A Novel Ag-N-Heterocyclic Carbene Complex Bearing the Hydroxyethyl Ligand: Synthesis, Characterization, Crystal and Spectral Structures and Bioactivity Properties

by
Aydin Aktas
1,
Duygu Barut Celepci
2,
Yetkin Gok
1,
Parham Taslimi
3,
Hulya Akincioglu
4 and
İlhami Gulcin
5,*
1
Department of Chemistry, Faculty of Arts and Sciences, Inonu University, 44280-Malatya, Turkey
2
Department of Physics, Faculty of Science, Dokuz Eylul University, 35160-Buca, İzmir, Turkey
3
Department of Biotechnology, Faculty of Science, Bartin University, 74100-Bartin, Turkey
4
Department of Chemistry, Faculty of Sciences and Arts, Agri Ibrahim Cecen University, 04100-Agri, Turkey
5
Department of Chemistry, Faculty of Sciences, Ataturk University, 25240-Erzurum, Turkey
*
Author to whom correspondence should be addressed.
Crystals 2020, 10(3), 171; https://0-doi-org.brum.beds.ac.uk/10.3390/cryst10030171
Submission received: 30 January 2020 / Revised: 24 February 2020 / Accepted: 1 March 2020 / Published: 5 March 2020
(This article belongs to the Section Biomolecular Crystals)
Browse Figures
Versions Notes

Abstract

:
In this study, a novel silver N-heterocyclic carbene (Ag-NHC) complex bearing hydroxyethyl substituent has been synthesized from the hydroxyethyl-substituted benzimidazolium salt and silver oxide by using in-situ deprotonation method. A structure of the Ag-NHC complex was characterized by using UV-Vis, FTIR, 1H-NMR and 13C-NMR spectroscopies and elemental analysis techniques. Also, the crystal structure of the novel complex was determined by single-crystal X-ray diffraction method. In this paper, compound 1 showed excellent inhibitory effects against some metabolic enzymes. This complex had Ki of 1.14 0.26 µM against human carbonic anhydrase I (hCA I), 1.88±0.20 µM against human carbonic anhydrase II (hCA I), and 10.75±2.47 µM against α-glycosidase, respectively. On the other hand, the Ki value was found as 25.32±3.76 µM against acetylcholinesterase (AChE) and 41.31±7.42 µM against butyrylcholinesterase (BChE), respectively. These results showed that the complex had drug potency against some diseases related to using metabolic enzymes.

1. Introduction

Medical applications of the silver metal were discovered a long time ago [1]. The most commonly used of silver compounds are silver nitrate and silver sulfonamides [2]. Today, most organisms have been known to develop antimicrobial resistance to drugs. Therefore, researchers have tried to develop novel, stronger and multimodal alternatives that have the least antibiotic effects on the human body [3]. At the clinical stage, silver has been shown to exhibit broad activity against antibiotics including those resistant to deadly microbes [4]. In recent studies, silver complexes exhibit less toxicity to the human body than other metal complexes, which have made them desirable antimicrobial substances [5].
The organic ligands, which coordinated to the silver metal center, make important contributions to biological activity. Among them, N-heterocyclic carbenes (NHCs) are one of the most important organic ligands. Transition metal complexes bearing NHC ligand have wide application areas. Biological activity applications of Ag-NHC complexes from these compounds have drawn attention. Furthermore, the biological activity applications of Ag-NHC complexes have started recently [2] and the number of studies on this subject is increasing day by day. In many studies, Ag-NHC complexes bearing functionalized NHC ligands exhibited promising biological activities [6,7]. In addition, the electronic and structural properties of NHCs and their modification properties have affected the biological activities of Ag-NHC complexes [8,9,10,11].
Carbonic anhydrases (CAs) are a structurally different enzyme family that catalyzes the interconversion of CO2 to HCO3−. This reaction influences physiological pH values and the supply of HCO3− ions and for plenty of metabolic, physiological, and biosynthetic pathways. The CA enzymes have a very active research area among medicinal chemists because designing CA inhibitors (CAIs) plays an important role in the therapy of some metabolic diseases including glaucoma, idiopathic intracranial hypertension, epilepsy, and altitude sickness [12,13,14,15].
The primary effect of AChE is the cancellation of nerve impulse conduction by the rapid hydrolysis of acetylcholine (ACh) in cholinergic synapses. Inhibition of this metabolic enzyme acts as a strategy for the duration of senile dementia, Parkinson’s disease, ataxia, Alzheimer’s disease (AD), myasthenia gravis and some disorders of autonomic nervous system functions. BChE is distinguished from AChE by its catalytic selectivity for butyrylcholine over acetylcholine hydrolysis. Looking at the points where they were synthesized, AChE is synthesized in muscle, nerve, and some hematopoietic cells. In excitable tissues, AChE is localized on the extracellular surface of both muscle and nerve and regulated by tissue-specific development. On the other hand, BChE is synthesized and released largely in the liver and is transported to the plasma. It is thought to play a primary role in the metabolism of dietary esters, perhaps only in selected species. Recently, a large spectrum of AChE inhibitors have been developed and approved to the treat AD, such as donepezil, physostigmine, rivastigmine, huperzine-A, galantamine and tacrine. These clinical drugs are capable to prevent the degradation of ACh and increase its level in the cholinergic synapses that can improve cognitive deficits. However, the adverse and undesired effects like nausea, vomiting and weight loss have limited their clinical usage and efficacy. So, it is necessary to develop novel cholinergic enzymes inhibitors with less toxic side effect and better therapeutic effect [16,17,18].
α-Glycosidase is a digestion enzyme that hydrolyzes polysaccharides like disaccharides and starches to generate more metabolically available sugar units in the course of catabolic metabolism. Indeed, it can functionally hydrolyze carbohydrate molecules; the α-glycosidase enzyme is distinct from β-glycosidase, which cleaves glycosides bonds. It is recorded that α-glycosidase is associated with type-2 diabetes mellitus (T2DM) due to the fact that the high activity of this enzyme raised plasma glucose level and affects glucose absorption in these patients [19,20,21,22].
Recently, our work group investigated the enzyme inhibition activities of NHC precursors [23,24,25,26] and Pd(II)NHC complexes [27,28,29,30]. In this context, we synthesized a novel Ag-NHC complex and characterized its structure by using UV-Vis, FTIR, 1H-NMR, and 13C-NMR spectroscopies and elemental analysis techniques. Further, we confirmed the structure of the novel Ag-NHC complex by using the single-crystal X-ray diffraction method. Finally, we investigated the inhibition effect of the novel Ag-NHC complex 1 against some metabolic enzymes.

2. Materials and Methods

The synthesis for the novel hydroxyethyl-liganded Ag-NHC complex 1 was prepared by using standard Schlenk techniques under an inert atmosphere. Any drying and purification weren’t applied for all solvents purchased. All reagents were economically accessible by Merck and Sigma-Aldrich (Darmstadt, Germany), and abcr chemical Co (Karlsruhe, Germany). The starting benzimidazolium salt [28], which used in the synthesis of the novel Ag-NHC complex 1 was synthesized in Inonu University Organometallic Research Laboratory in Malatya, Turkey. The melting point was recognized in glass capillaries under air with an Electrothermal-9200 melting point apparatus (Giessen, Germany). Also, FTIR spectra assay were kept in the range 400–4000 cm−1 on Perkin Elmer Spectrum 100 FTIR spectrometer (Waltham, MA, USA). The UV spectrum was measured with Shimadzu UV-1601 instrument (Duisburg, Germany). The 1H and 13C NMR spectra were recorded using either a Bruker 400 Merkur spectrometer (Billerica, MA, USA) operating at 1H NMR (400 MHz) and 13C NMR (100 MHz) in DMSO-d6 with tetramethylsilane as an internal reference by Inonu University Catalysis Research and Application Center in Malatya, Turkey. Elemental analyses were performed by Inonu University Scientific and Technology Centre (Malatya, Turkey) on LECO, CNHS932 Elemental Analyzers (Haan, Germany).

2.1. Synthesis of Ag-NHC Complex 1

For the preparation of Ag-NHC complex 1; the 1-(2-hydroxyethyl)-3-ethylbenzimidazolium bromide (0.379 g, 1.4 mmol) and silver(I)oxide (Ag2O) (0.162 g, 0.7 mmol) were reacted in dichloromethane (30 mL). To the reaction mixture were added activated molecular sieves (4 units). The mixture was stirred in dark for 48 h. at room temperature. The mixture was filtered through celite (1 cm thick) and the solvent in the mixture was evaporated under vacuum. Then, the product was obtained as a white solid, which recrystallized from dichloromethane/ diethyl ether (1:3) at room temperature [31]. Yield: 80% (371 mg); m.p.: 158–159 °C; ν(CN for 2-C): 1397 cm−1; ν(OH): 3157–3537 cm−1. Anal. Calc. for C44H56Ag3Br3N8O4: C: 39.91; H: 4.26; N: 8.46. Found: C: 38.98, H: 4.02, N: 8.23. 1H NMR (400 MHz, DMSO-d6); δ 1.48 (t, 3H, J = 7.2 Hz, -NCH2CH3); 3.87 (t, 2H, J = 5.2 Hz, -NCH2CH2OH); 4.53–4.59 (m, 4H, -NCH2CH2OH and -NCH2CH3); 5.12 (s, 1H, -NCH2CH2OH); 7.42–7.83 (m, 4H, Ar–H). 13C NMR (100 MHz, DMSO-d6); δ 16.5 (-NCH2CH3); 44.2 (-NCH2CH3); 51.7 (-NCH2CH2OH); 60.9 (-NCH2CH2OH); 112.2, 112.4, 112.8, 124.1, 124.2, 124.3, 133.3, 133.4 and 134.4. (Ar–C); 190.0 (Ag–Ccarbene).

2.2. Biochemical Studies

The inhibiting effects of the Ag-NHC complex 1 on both carbonic anhydrase isoenzymes (hCA I and II) are described by Verpoorte et al. [32] and detailed in previous studies [33,34] and recorded spectrophotometrically using p-nitrophenylacetate substrate (PNA) at 348 nm [35,36]. Indeed, the BChE and AChE inhibitory effects of Ag-NHC complex 1 were performed according to the Ellman’s assay [37] and spectrophotometrically recorded at 412 nm [38]. Butyrylthiocholine iodide and acetylthiocholine iodide was substrates for both enzymatic reaction. On the other hand, 5,5′-dithio-bis (2-nitro-benzoic) acid molecule was used to measure AChE and BChE activities, respectively [39]. Additionally, the α-glycosidase inhibitory effect of Ag-NHC complex 1 was carried out using the p-nitrophenyl-D-glycopyranoside molecule (p-NPG) as the substrate according to the method of Tao et al. [40] Samples of this work were prepared by dissolving as mg/mL. This assay was performed according to previous studies [41,42].

2.3. X-ray Crystallography

X-ray single crystal diffraction data for Ag-NHC complex 1 was collected at room temperature on a Rigaku-Oxford Xcalibur diffractometer (Oxford, UK) with an EOS-CCD detector using graphite-monochromatic MoKα radiation (λ = 0.71073 Å) with CrysAlisPro software (Oxford, UK) [43]. Data reduction and analytical absorption correction were performed by CrysAlisPro program [44]. Utilizing Olex2 [45], structure was solved using Intrinsic Phasing method with SHELXT [46] and refined by full-matrix least squares on F2 in SHELXL [47]. Anisotropic thermal parameters were applied to all non-hydrogen atoms. All hydrogen atoms were placed using standard geometric models and with their thermal parameters riding on those of their parent atoms. Some positional disorders were observed for hydroxyethyl groups in the structure, and to ensure satisfactory refinement of these disordered hydroxyethyl groups, constraint and restraint instructions such as EADP, DFIX, and DELU were applied. A summary of crystal data, experimental details, and refinement results for the Ag-NHC complex 1 is given in Table 1. Crystallographic data as cif file for the structure reported in this paper has been deposited at the Cambridge Crystallographic Data Center with CCDC 1979850 for complex 1. Copies of the data can be obtained free of charge at http://www.ccdc.cam.ac.uk/conts/retrieving.html or from the Cambridge Crystallographic Data Center, 12, Union Road, Cambridge CB2 1EZ, UK. Fax: (+44) 1223-336-033, email: [email protected].

3. Results and Discussion

3.1. Synthesis

The Ag-NHC complex 1 bearing hydroxyethyl-liganded have illustrated in Scheme 1. The complex was synthesized from the hydroxyethyl-substituted benzimidazolium salt [28] and silver oxide via in-situ deprotonation method. The reaction mixture was stirred in dark during 48 h. at room temperature. The Ag-NHC complex 1 was obtained as a white solid at 80% yield. The novel stable complex was well soluble in halogenated solvents such as dichloromethane and chloroform. Also, the Ag-NHC complex 1 was well soluble in polar solvents such as dimethylsulfoxide and dimethylformamide. But, this complex was less soluble in polar solvents such as water and ethanol.

3.2. NMR Study

The structure of the Ag-NHC complex 1 was characterized by 1H NMR and 13C NMR spectroscopic methods. When the 1H NMR data was examined, the characteristic proton peak that observed at 10.42 ppm for the starting benzimidazolium salt [28] was not observed in the novel Ag-NHC complex. The -CH3 and -CH2 proton peaks belonging to the ethyl group (-NCH2CH3) have been observed as triplets at 1.48 ppm (J = 7.2 Hz) and as multiplets at 4.55 ppm, respectively. The two -CH2 proton peaks belonging to the hydroxyethyl group (-NCH2CH2OH) have been observed as triplet at 3.87 ppm (J = 5.2 Hz) and as multiplets at 4.58 ppm respectively. The broad (wide) singlet peak was observed at 5.12 ppm for hydroxy proton in the 1H NMR spectrum. The aromatic proton peaks of benzimidazole have observed as multiplited between 7.42 and 7.83 ppm. When the 13C NMR data was examined, the characteristic carbon peak that observed at 141.7 ppm for the 2-CH of the starting benzimidazolium salt [28] was not observed in the novel Ag-NHC complex. Furthermore, the characteristic Ag–Ccarbene resonance for the novel Ag-NHC complex 1 was observed in the 13C NMR spectra appeared highly downfield at 190.0 ppm. The -CH2 aliphatic carbon atom bonding to -OH on the hydroxyethyl group has been observed at 60.9 ppm. The -CH2 aliphatic carbon atom bonding to the nitrogen on the hydroxyethyl group (-NCH2CH2OH) has been observed at 51.7 ppm. The -CH3 and -CH2 aliphatic carbon peaks belonging to the ethyl group (-NCH2CH3) have been observed at 16.5 and 44.2 ppm respectively. The aromatic carbon peaks of benzimidazole observed between 112.2 and 134.4 ppm. All 1H NMR data (Figure 1) and 13C NMR data (Figure 2) for the novel Ag-NHC complex 1 have compatible with the literature [6,7].

3.3. FTIR Study

Herein, the FTIR spectroscopy has been used to describe the functional groups available in the complex. The FTIR spectrum of the novel Ag-NHC complex 1 has illustrated in Figure 3. It has been recorded for the wavenumbers region between 4000 and 450 cm−1. When the investigation of the FTIR spectrum, the symmetrical C–H stretching frequency of the benzene rings observed intense at 3119 and 3155 cm−1. The symmetrical C–H stretching frequency of the –CH2– and -CH3 groups in the ethyl and the –CH2– groups in the hydroxyethyl becomes intense at 2869, 2934 and 2975 cm−1. The symmetrical C=C–C stretching frequency of the benzene rings become intense at 1555 cm−1. The symmetrical conjugated C=C bond stretching frequency of the benzene rings becomes intense at 1344 cm−1. The band at 1039 cm−1 and 1054 cm−1 corresponds to the primary alcohol (hydroxyethyl group) C–O stretching mode. The band at 1288 cm−1 corresponds to the primary alcohol (hydroxyethyl group) O–H in-plane bending vibration. The symmetrical for Ccarbene–N stretching frequency in the benzimidazole group observed intense at 1397 cm−1 [48,49]. According to the literature, Ag–C stress vibrations are expected in the frequency region of 400–155 cm−1 [50].

3.4. UV-Vis Study

The UV-Vis spectra of the novel Ag-NHC complex of dissolved in chloroform at 25 °C showed up four absorption bands at 220, 250, 270 and 320 nm, respectively. The UV-Vis spectra of the novel Ag-NHC complex 1 were recorded in (CHCl3) solutions at a concentration of 15 or 10 µM and were depicted in Figure 4 with a range 200~400 nm. The novel Ag-NHC complex 1 showed a new absorption peak at 320 related to MLCT (metal-ligand charge transfer) (Ag+ to NHC ligand) (Figure 4) [51]. This peak is known as the wide range bands, both π → π *, n → π * and d-d transitions of (C = N) and charge-transfer transition arising from π electron interactions between metal and ligand that involves either a metal-to-ligand or ligand-to-metal electron transfer [52]. The absorption bands below 220~270 nm in CHCl3 are practically identical and can be attributed to π → π* transitions in the benzene and benzimidazole ring [51,53].

3.5. Description of the Crystal Structure of Ag-NHC Complex 1

A molecular representation of the Ag-NHC complex 1 is depicted in Figure 5. The asymmetric unit of the Ag-NHC complex 1 contains a half of molecule and completed with Ci symmetry operation. The coordination environment comprises of a nearly linear [Ag(NHC)2]+ cation and a [AgBr]-anion with an almost perpendicular orientation to the cation [C1–Ag1–Ag2–Br1 = 90.2(2)°, C12–Ag1–Ag2–Br1 = −87.8(2)°]. There is also a bromide ion in the asymmetric unit, connected to the cation molecule with a hydrogen bond. The angle C1–Ag1–C12 is 171.1(3)° and deviates from the linear geometry. The Ag1…Ag2 association is 3.097(6) Å, is almost low comparing the Ag…Ag bond distances in the literature [54]. The cationic Ag–C bond distances are consistent with the similar Ag(NHC) complexes [Ag1–C1 2.098(7) Å, Ag1–C12 2.096(8) Å] [55]. The interplanar angle between the benzimidazole (C1) ring and the C1–Ag1–Ag2 plane is 79.50(16)° and that between benzimidazole (C12) ring and the C12–Ag1–Ag2 plane is 76.95(17)°.
In the crystal packing of the complex 1, cation molecules linked to each other via bromide anions with O1–H1∙∙∙Br2i [H1∙∙∙Br2 = 2.58 Å, O1–Br2 = 3.15(3) Å, O1–H1∙∙∙Br2 = 127°, symmetry code: i 3/2 − x, −1/2 + y, 3/2 − z]; O2A–H2AA∙∙∙Br2 [H2AA∙∙∙Br2 = 2.25 Å, O2A–Br2 = 3.04(2) Å, O2A–H2AA∙∙∙Br2 = 163°] and O2B–H2BA∙∙∙Br2 [H2BA∙∙∙Br2 = 2.17 Å, O2B–Br2 = 2.89(3) Å, O2B–H2BA∙∙∙Br2 = 147°] hydrogen bonding interactions forming an infinite chain along the b- and c-axis. The crystal structure is also stabilized by C–H∙∙∙Br and C–H∙∙∙O type intra- and intermolecular weak interactions. As can be seen in Figure 6, the Ag2 atoms settle in each corner of the unit cell and one is in the middle of the unit cell, while the bromide anions are between these corners Ag2 atoms.

3.6. Enzyme Inhibition Studies

Inhibitors of metabolic enzymes can constitute new therapeutics against cancer or may have potential as antibacterial and antifungal drugs [56,57]. Recently, the inhibition of human CAs by sulfonamide compounds has been recorded to inhibit the growth of pathogenic microorganisms. Selective inhibition of CA II constitutes a viable approach to fight against the disturbances caused by the harmful effects of CA II enzyme [58,59,60]. When testing the results, the following inhibition activity relevance could be considered and summarized:
  • For the hCA I isoenzyme, Ag-NHC complex 1 had Ki and IC50 values of 1.14±0.26 and 0.93 µM, respectively (Table 2). Additionally, for the hCA II isoform, Ag-NHC complex 1 had Ki and IC50 values 1.88±0.20 and 1.26 nM, respectively (Table 2). In this work, acetazolamide (AZA) as a positive CA inhibitor, which used for therapy of epileptic seizure, altitude sickness, glaucoma, dural ectasia, and idiopathic intracranial hypertension, had IC50 values of 54.88 and 48.22 µM for hCA I, and hCA II. Also, AZA showed Ki values of 50.17±4.17 and 42.15±8.11 µM against both isoenzymes, respectively (Table 2). IC50 values of Ag-NHC complex 1 and AZA exhibited the following order: Ag-NHC complex 1 (0.9300, r2: 0.9786 µM) < AZA (54.88, r2: 0.9880 µM) for hCA I while these compound exhibited for hCA II the following order: Ag-NHC complex 1 (1.26 µM, r2: 0.9435 µM) < AZA (48.22 nM, r2: 0.9878 µM).
  • There are multiple synthetical drugs like tacrine, donepezil, and rivastigmine based on for the duration of cognitive dysfunction and memory loss related to AD. These components have been reported to have side effects such as gastrointestinal disorders related to biocompatibility issues [61,62,63]. Ag-NHC complex 1 effectively inhibited both cholinergic BChE and AChE enzymes. It was obtained that Ki values were 25.32±3.76 µM for AChE and 41.31±7.42 µM for BChE, respectively (Table 2). In addition, Tacrine (TAC) was used as positive control BChE and AChE inhibitor it had Ki values 47.18±8.37 and 69.08±13.40 µM, respectively. IC50 values of Ag-NHC complex 1 and Tacrine exhibited the following order: Ag-NHC complex 1 (36.41 µM, r2: 0.9745) < Tacrine (76.20 µM, r2: 0.9874) for AChE while these compound exhibited for BChE the following order: Ag-NHC complex 1 (50.25 µM, r2: 0.9790) < Tacrine (96.40 µM, r2: 0.9424).
  • The α-glycosidase inhibitors as oral antidiabetic compounds, which inhibit upper gastrointestinal enzymes that break down the carbohydrate polysaccharides into glucose units. Indeed, the absorption of glucose is delayed postprandial glucose levels [64,65,66,67]. For glycosidase, Ag-NHC complex 1 and acarbose have IC50 values of 8.11 (r2: 0.9252) and 22.80 µM, respectively. Their Ki values were found as 10.75±2.47 and 12.60±0.70 µM, respectively. (Table 2). The results have clearly documented that Ag-NHC complex 1 had shown effective inhibitory effects against α-glycosidase inhibition than that of acarbose (IC50: 22.80 µM) as a standard α-glycosidase inhibitor [40]. IC50 values of Ag-NHC complex 1 and acarbose exhibited the following order: Ag-NHC complex 1 (8.11 µM, r2: 0.9252) < Acarbose for α-glycosidase [68,69].

4. Conclusions

Consequently, in this study, a novel hydroxyethyl-substituted Ag-NHC complex 1 was synthesized and has been fully characterized by using FT-IR, 1H NMR, 13C NMR, and UV-Vis spectroscopy and elemental analysis techniques. As a result of all characterization data, the novel Ag-NHC complex 1 exhibited great compatibility with the proposed formulas. Single-crystal X-ray diffraction analysis displayed the T-shaped geometry for a three-coordinate silver atom. Bromide anions play a bridge role to connect the molecules and occur one-dimensional infinite chain along the b-axis. Ag-NHC complex 1 was found to be a good inhibitor for hCA I and hCA II isoenzymes, α-glycosidase, AChE and BChE enzymes. This type of compound can be used for the development of novel antiglaucoma, antiepileptic, anticholinesterase, and anticancer drugs.

Author Contributions

Investigation, A.A., P.T., H.A.; writing-original draft preparation, D.B.C.; writing—review and editing, Y.G., İ.G. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Acknowledgments

The authors thank the Inonu University Faculty of Science Department of Chemistry for the characterization of compounds and Inonu University Technology Center for the elemental analyses of the complex. The authors also acknowledge Dokuz Eylül University for the use of the Oxford Rigaku Xcalibur Eos Diffractometer (purchased under University Research Grant No: 2010.KB.FEN.13).

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Asekunowo, P.O.; Haque, R.A. Counterion-induced modulation in biochemical properties of nitrile functionalized silver (I)-N-heterocyclic carbene complexes. J. Coord. Chem. 2014, 67, 3649–3663. [Google Scholar] [CrossRef]
  2. Melaiye, A.; Simons, R.S.; Milsted, A.; Pingitore, F.; Wesdemiotis, C.; Tessier, C.A.; Youngs, W.J. Formation of water-soluble pincer Silver(I)-Carbene complexes:  A novel antimicrobial agent. J. Med. Chem. 2004, 47, 973–977. [Google Scholar] [CrossRef] [PubMed]
  3. Habib, A.; Iqbal, M.A.; Bhatti, H.N.; Kamal, A.; Kamal, S. Synthesis of alkyl/aryl linked binuclear Silver(I)-N-heterocyclic carbene complexes and evaluation of their antimicrobial, hemolytic and thrombolytic potential. Inorg. Chem. 2020, 111, 107670. [Google Scholar] [CrossRef]
  4. Haque, R.A.; Iqbal, M.A.; Mohamad, F.; Razali, M.R. Antibacterial and DNA cleavage activity of carbonyl functionalized N-heterocyclic carbene-silver (I) and selenium compounds. J. Mol. Struct. 2018, 1155, 362–370. [Google Scholar] [CrossRef]
  5. Alisir, S.H.; Sariboga, B.; Caglar, S.; Buyukgungor, O. Synthesis, characterization, photoluminescent properties and antimicrobial activities of two novel polymeric silver (I) complexes with diclofenac. J. Mol. Struct. 2017, 1130, 156–164. [Google Scholar] [CrossRef]
  6. Yıldırım, I.; Aktas, A.; Barut Celepci, D.; Kırbag, S.; Kutlu, T.; Gok, Y.; Aygün, M. Synthesis, characterization, crystal structure, and antimicrobial studies of 2-morpholinoethylsubstituted benzimidazolium salts and their silver(I)-N-heterocyclic carbene complexes. Res. Chem. Intermed. 2017, 43, 6379–6393. [Google Scholar]
  7. Aktas, A.; Keleştemur, U.; Gok, Y.; Balcıoglu, S.; Ates, B.; Aygun, M. 2-Morpholinoethyl-substituted N-heterocyclic carbene (NHC) precursors and their silver(I)NHC complexes: Synthesis, crystal structure and in vitro anticancer properties. J. Iran. Chem. Soc. 2018, 15, 131–139. [Google Scholar] [CrossRef]
  8. Öfele, K. 1,3-Dimethyl-4-imidazolinyliden-(2)-pentacarbonylchrom ein neuer übergangsmetall carben komplex. J. Organomet. Chem. 1968, 12, 42–43. [Google Scholar] [CrossRef]
  9. Wanzlick, H.W.; Schönherr, H.J. Direct synthesis of a mercury salt-carbene complex. Angew. Chem. 1968, 7, 141–142. [Google Scholar] [CrossRef]
  10. Gok, Y.; Aktaş, A.; Erdoğan, H.; Sarı, Y. New 4-vinylbenzyl-substituted bis(NHC)-Pd(II) complexes: Synthesis, characterization and the catalytic activity in the direct arylation reaction. Inorg. Chim. Acta 2018, 471, 735–740. [Google Scholar] [CrossRef]
  11. Erdogan, H.; Aktas, A.; Gok, Y.; Sarı, Y. N-Propylphthalimide-substituted bis-(NHC)PdX2 complexes: Synthesis, characterization and catalytic activity in direct arylation reactions. Transit. Met. Chem. 2018, 43, 31–37. [Google Scholar] [CrossRef]
  12. Aksu, K.; Ozgeriş, B.; Taslimi, P.; Naderi, A.; Gulcin, I.; Goksu, S. Antioxidant activity, acetylcholinesterase and carbonic anhydrase inhibitory properties of novel ureas derived from phenethylamines. Arch. Pharm. 2016, 349, 944–954. [Google Scholar] [CrossRef] [PubMed]
  13. Altay, A.; Tohma, H.; Durmaz, L.; Taslimi, P.; Korkmaz, M.; Gulcin, I.; Koksal, E. Preliminary phytochemical analysis and evaluation of in vitro antioxidant, antiproliferative, antidiabetic and anticholinergics effects of endemic Gypsophila taxa from Turkey. J. Food Biochem. 2019, 43, e12908. [Google Scholar] [CrossRef] [PubMed]
  14. Atmaca, U.; Yıldırım, A.; Taslimi, P.; Tuncel Çelik, S.; Gulcin, I.; Supuran, C.T.; Çelik, M. Intermolecular amination of allylic and benzylic alcohols leads to effective ınhibitions of acetylcholinesterase enzyme and carbonic anhydrase I and II isoenzymes. J. Biochem. Mol. Toxicol. 2018, 32, e22173. [Google Scholar] [CrossRef] [PubMed]
  15. Bayrak, C.; Taslimi, P.; Gulcin, I.; Menzek, A. The first synthesis of 4-phenylbutenone derivative bromophenols including natural products and their inhibition profiles for carbonic anhydrase, acetylcholinesterase and butyrylcholinesterase enzymes. Bioorg Chem. 2017, 72, 359–366. [Google Scholar] [CrossRef] [PubMed]
  16. Bayrak, C.; Taslimi, P.; Kahraman, H.S.; Gulcin, I.; Menzek, A. The first synthesis, carbonic anhydrase inhibition and anticholinergic activities of some bromophenol derivatives with S including natural products. Bioorg. Chem. 2019, 85, 128–139. [Google Scholar] [CrossRef]
  17. Ozmen Ozgun, D.; Yamali, C.; Gul, H.I.; Taslimi, P.; Gulcin, I.; Yanik, T.; Supuran, C.T. Inhibitory effects of isatin Mannich bases on carbonic anhydrases, acetylcholinesterase and butyrylcholinesterase. J. Enzyme Inhib. Med. Chem. 2016, 31, 1498–1501. [Google Scholar] [CrossRef] [Green Version]
  18. Bicer, A.; Taslimi, P.; Yakalı, G.; Gulcin, I.; Gultekin, M.S.; Cin, G.T. Synthesis, characterization, crystal structure of novel bis-thiomethylcyclohexanone derivatives and their inhibitory properties against some metabolic enzymes. Bioorg. Chem. 2019, 82, 393–404. [Google Scholar] [CrossRef]
  19. Burmaoglu, S.; Yilmaz, A.O.; Taslimi, P.; Algul, O.; Kılıç, D.; Gulcin, I. Synthesis and biological evaluation of phloroglucinol derivatives possessing α-glycosidase, acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase inhibitory activity. Arch. Pharm. 2018, 351, e1700314. [Google Scholar] [CrossRef]
  20. Bursal, E.; Aras, A.; Kılıc, Ö.; Taslimi, P.; Gören, A.C.; Gulcin, I. Phytochemical content, antioxidant activity and enzyme inhibition effect of Salvia eriophora Boiss. & Kotschy against acetylcholinesterase, α-amylase, butyrylcholinesterase and α-glycosidase enzymes. J. Food Biochem. 2019, 43, e12776. [Google Scholar]
  21. Caglayan, C.; Demir, Y.; Kucukler, S.; Taslimi, P.; Kandemir, F.M.; Gulcin, I. The effects of hesperidin on sodium arsenite-induced different organ toxicity in rats on metabolic enzymes as antidiabetic and anticholinergics potentials: A biochemical approach. J. Food Biochem. 2019, 43, e12720. [Google Scholar] [CrossRef]
  22. Caglayan, C.; Taslimi, P.; Demir, Y.; Kucukler, S.; Kandemir, M.F.; Gulcin, I. The effects of zingerone against vancomycin-induced lung, liver, kidney and testis toxicity in rats: The behavior of some metabolic enzymes. J. Biochem. Mol. Toxicol. 2019, 33, e22381. [Google Scholar] [CrossRef]
  23. Aktas, A.; Taslimi, P.; Gok, Y.; Gulcin, I. Novel NHC precursors: Synthesis, characterization, and carbonic anhydrase and acetylcholinesterase inhibitory properties. Arch. Pharm. 2017, 350, e1700045. [Google Scholar] [CrossRef] [PubMed]
  24. Erdemir, F.; Barut Celepci, D.; Aktas, A.; Taslimi, P.; Gok, Y.; Karabıyık, H.; Gulcin, I. 2-Hydroxyethyl substituted NHC precursors: Synthesis, characterization, crystal structure and carbonic anhydrase, a-glycosidase, butyrylcholinesterase, and acetylcholinesterase inhibitory properties. J. Mol. Struct. 2018, 1155, 797–806. [Google Scholar] [CrossRef]
  25. Türker, F.; Barut Celepci, D.; Aktas, A.; Taslimi, P.; Gok, Y.; Aygün, M.; Gulcin, I. Meta-cyanobenzyl substituted benzimidazolium salts: Synthesis, characterization, crystal structure and carbonic anhydrase, α-glycosidase, butyrylcholinesterase, and acetylcholinesterase inhibitory properties. Arch. Pharm. 2018, 351, 1800029. [Google Scholar]
  26. Behcet, A.; Caglılar, T.; Barut, C.D.; Aktas, A.; Taslimi, P.; Gok, Y.; Aygun, M.; Kaya, R.; Gulcin, I. Synthesis, characterization and crystal structure of 2-(4-hydroxyphenyl)ethyl and 2-(4-nitrophenyl)ethyl Substituted Benzimidazole Bromide Salts: Their inhibitory properties against carbonic anhydrase and acetylcholinesterase. J. Mol. Struct. 2018, 1170, 160–169. [Google Scholar] [CrossRef]
  27. Aktas, A.; Barut Celepci, D.; Kaya, R.; Taslimi, P.; Gok, Y.; Aygun, M.; Gulcin, I. Novel morpholine liganded Pd-based N-heterocyclic carbene complexes: Synthesis, characterization, crystal structure, antidiabetic and anticholinergic properties. Polyhedron 2019, 159, 345–354. [Google Scholar] [CrossRef]
  28. Aktas, A.; Noma, S.A.A.; Barut Celepci, D.; Erdemir, F.; Gok, Y.; Ates, B. New 2-hydroxyethyl substituted n-heterocyclic carbene precursors: Synthesis, characterization, crystal structure and inhibitory properties against carbonic anhydrase and xanthine oxidase. J. Mol. Struct. 2019, 1184, 487–494. [Google Scholar] [CrossRef]
  29. Erdemir, F.; Barut Celepci, D.; Aktas, A.; Gok, Y.; Kaya, R.; Taslimi, P.; Demir, Y.; Gulcin, I. Novel 2-aminopyridine liganded Pd(II)N-heterocyclic carbene complexes: Synthesis, characterization, crystal structure and bioactivity properties. Bioorg. Chem. 2019, 91, 103134. [Google Scholar] [CrossRef]
  30. Bal, S.; Aktas, A.; Kaya, R.; Gok, Y.; Karaman, M.; Taslimi, P.; Gulcin, I. Novel 2-methylimidazolium salts: Synthesis, characterization, molecular docking, and carbonic anhydrase and acetylcholinesterase inhibitory properties. Bioorg. Chem. 2020, 94, 103468. [Google Scholar] [CrossRef]
  31. Aktas, A.; Gok, Y. N-Propylphthalimide-substituted Silver(I) N-heterocyclic carbene complexes and Ruthenium(II) N-heterocyclic carbene complexes: Synthesis and transfer hydrogenation of ketones. Trans. Met. Chem. 2014, 39, 925–931. [Google Scholar] [CrossRef]
  32. Verpoorte, J.A.; Mehta, S.Ç.; Edsall, J.T. Esterase activities of human carbonic anhydrases B and C. J. Biol. Chem. 1967, 242, 4221–4229. [Google Scholar] [PubMed]
  33. Hisar, O.; Beydemir, Ş.; Gulcin, I.; Kufrevioglu, O.I.; Supuran, C.T. Effect of low molecular weight plasma inhibitors of rainbow trout (Oncorhyncytes mykiss) on human erythrocytes carbonic anhydrase-II isozyme activity in vitro and rat erythrocytes in vivo. J. Enzyme Inhib. Med. Chem. 2005, 20, 35–39. [Google Scholar] [CrossRef] [PubMed]
  34. Caglayan, C.; Taslimi, P.; Türk, C.; Kandemir, F.M.; Demir, Y.; Gulcin, I. Purification and characterization of the carbonic anhydrase enzyme from horse mackerel (Trachurus trachurus) muscle and the impact of some metal ions and pesticides on enzyme activity. Comp. Biochem. Physiol. 2019, 226, 108605. [Google Scholar] [CrossRef]
  35. Ozbey, F.; Taslimi, P.; Gulcin, I.; Maras, A.; Goksu, S.; Supuran, C.T. Synthesis, acetylcholinesterase, butyrilcholinesterase, carbonic anhydrase inhibitory and metal chelating properties of some novel diaryl ether. J. Enzyme Inhib. Med. Chem. 2016, 31, 79–85. [Google Scholar] [CrossRef] [Green Version]
  36. Oztaskın, N.; Taslimi, P.; Maras, A.; Goksu, S.; Gulcin, I. Novel antioxidant bromophenols with acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase inhibitory actions. Bioorg. Chem. 2017, 74, 104–114. [Google Scholar]
  37. Ellman, G.L.; Courtney, K.D.; Andres, V.; Featherston, R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 1961, 7, 88–95. [Google Scholar] [CrossRef]
  38. Cetin, A.; Turkan, F.; Taslimi, P.; Gulcin, I. Synthesis and characterization of novel substituted thiophene derivatives and discovery of their carbonic anhydrase and acetylcholinesterase ınhibition effects. J. Biochem. Mol. Toxicol. 2019, 33, e22261. [Google Scholar] [CrossRef]
  39. Daryadel, S.; Atmaca, U.; Taslimi, P.; Gulcin, I.; Celik, M. Novel sulfamate derivatives of menthol: Synthesis, characterization, and cholinesterases and carbonic anhydrase enzymes inhibition properties. Arch. Pharm. 2018, 351, 1800209. [Google Scholar] [CrossRef]
  40. Tao, Y.; Zhang, Y.; Cheng, Y.; Wang, Y. Rapid screening and identification of α-glucosidase inhibitors from mulberry leaves using enzyme-immobilized magnetic beads coupled with HPLC/MS and NMR. Biomed. Chromatogr. 2013, 27, 148–155. [Google Scholar] [CrossRef]
  41. Demir, Y.; Durmaz, L.; Taslimi, P.; Gulcin, I. Anti-diabetic properties of dietary phenolic compounds: Inhibition effects on α-amylase, aldose reductase and α-glycosidase. Biotechnol. Appl. Biochem. 2019, 66, 781–786. [Google Scholar] [CrossRef] [PubMed]
  42. Demir, Y.; Taslimi, P.; Ozaslan, M.S.; Oztaskin, N.; Cetinkaya, Y.; Gulcin, I.; Beydemir, Ş.; Goksu, S. Antidiabetic potential: In vitro inhibition effects of bromophenol and diarylmethanones derivatives on metabolic enzymes. Arch. Pharm. 2018, 351, 1800263. [Google Scholar] [CrossRef] [PubMed]
  43. Rigaku Corporation. CrysAlis(Pro) Software System; Version 1.171.38.43; Rigaku Corporation: Oxford, UK, 2015. [Google Scholar]
  44. Clark, R.C.; Reid, J.S. The analytical calculation of absorption in multifaceted crystals. Acta Crystallogr. A Found. Crystallog. 1995, A51, 887–897. [Google Scholar] [CrossRef]
  45. Dolomanov, O.V.; Bourhis, L.J.; Gildea, R.J.; Howard, J.A.K.; Puschmann, H. OLEX2: A complete structure solution, refinement and analysis program. J. Appl. Cryst. 2009, 42, 339–341. [Google Scholar] [CrossRef]
  46. Sheldrick, G.M. SHELXT-integrated space-group and crystal-structure determination. Acta Crystallogr. A Found. Crystallogr. 2015, A71, 3–8. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  47. Sheldrick, G.M. Crystal structure refinement with SHELXL. Acta Crystallogr. C Struct. Chem. 2015, C71, 3–8. [Google Scholar] [CrossRef] [PubMed]
  48. Aktas, A.; Barut Celepci, D.; Gok, Y. Novel 2-hydroxyethyl substituted N-coordinate-Pd(II)(NHC) and bis(NHC)Pd(II) complexes: Synthesis, characterization and the catalytic activity in the direct arylation reaction. J. Chem. Sci. 2019, 131, 78. [Google Scholar] [CrossRef] [Green Version]
  49. Aktas, A. A new palladium complex containing mixture of carbene and phosphine ligands: Synthesis, crystal structures, spectral FTIR, NMR and UV-Vis researched. Chin. J. Struct. Chem. 2019, 38, 1664–1672. [Google Scholar]
  50. Ahmad, S.; Georgieva, I.; Hanif, M.; Monim-ul-Mehboob, M.; Munir, S.; Sohail, A.; Isab, A.A. Periodic DFT modeling and vibrational analysis of silver(I) cyanide complexes of thioureas. J. Mol. Model. 2019, 25, 90. [Google Scholar]
  51. Kılıc, A.; Tas, E.; Gumgum, B.; Yılmaz, I. Synthesis, Spectroscopic and electrochemical investigations of two vic-dioximes and their mononuclear Ni(II), Cu(II) and Co(II) metal complexes containing morpholine group. Chin. J. Chem. 2006, 24, 1599–16004. [Google Scholar]
  52. Sacconi, L.; Ciampolini, M.; Maffio, F.; Cavasino, F.P. Studies in coordination chemistry. IX.1 investigation of the stereochemistry of some complex compounds of cobalt(II) with N-substituted salicylaldimines. J. Am. Chem. Soc. 1962, 84, 3245–3248. [Google Scholar] [CrossRef]
  53. Aktas, A.; Barut Celepci, D.; Gök, Y. Synthesis, crystal structures, spectral FT-IR, NMR and UV-Vis investigations and Hirshfeld surface analysis of two new 2-hydroxyethyl substituted N-heterocyclic carbene (NHC) precursors. J. Chin. Chem. Soc. 2019, 66, 1389–1396. [Google Scholar] [CrossRef]
  54. Hirtenlehner, C.; Krims, C.; Hölbling, J.; List, M.; Zabel, M.; Fleck, M.; Berger, R.J.F.; Schoefbergera, W.; Monkowius, U. Syntheses, crystal structures, reactivity, and photochemistry of gold(III) bromides bearing N-heterocyclic carbenes. Dalton Trans. 2011, 40, 9899–9910. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  55. Saif, M.J.; Flowe, K.R. A general method for the preparation of N-heterocyclic carbene–Silver(I) complexes in water. Trans. Met. Chem. 2013, 38, 113–118. [Google Scholar] [CrossRef]
  56. Balaydin, H.T.; Gulcin, I.; Menzek, A.; Goksu, S.; Sahin, E. Synthesis and antioxidant properties of diphenylmethane derivative bromophenols including a natural product. J. Enzyme Inhib. Med. Chem. 2010, 25, 685–695. [Google Scholar] [CrossRef] [Green Version]
  57. Nar, M.; Cetinkaya, Y.; Gulcin, I.; Menzek, A. (3,4-Dihydroxyphenyl)(2,3,4-trihydroxyphenyl)methanone and its derivatives as carbonic anhydrase isoenzymes inhibitors. J. Enzyme Inhib. Med. Chem. 2013, 28, 402–406. [Google Scholar] [CrossRef]
  58. Ekiz, M.; Tutar, A.; Okten, S.; Butun, B.; Kocyigit, U.M.; Taslimi, P.; Topcu, G. Synthesis, characterization and SAR of arylated indenoquinolinebased cholinesterase and carbonic anhydrase inhibitors. Arch. Pharm. 2018, 351, 1800167. [Google Scholar] [CrossRef]
  59. Garibov, E.; Taslimi, P.; Sujayev, A.; Bingol, Z.; Cetinkaya, S.; Gulcin, I.; Beydemir, S.; Farzaliyev, V.; Alwasel, S.H.; Supuran, C.T. Synthesis of 4,5-disubstituted-2-thioxo-1,2,3,4-tetrahydropyrimidines and investigation of their acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase I/II inhibitory and antioxidant activities. J. Enzyme Inhib. Med. Chem. 2016, 31, 1–9. [Google Scholar] [CrossRef] [Green Version]
  60. Gocer, H.; Topal, F.; Topal, M.; Kucuk, M.; Teke, D.; Gulcin, I.; Alwasel, S.H.; Supuran, C.T. Acetylcholinesterase and carbonic anhydrase isoenzymes I and II inhibition profiles of taxifolin. J. Enzyme Inhib. Med. Chem. 2016, 31, 441–447. [Google Scholar] [CrossRef]
  61. Genc Bilgicli, H.; Kestane, A.; Taslimi, P.; Karabay, O.; Bytyqi-Damoni, A.; Zengin, M.; Gulcin, I. Novel eugenol bearing oxypropanolamines: Synthesis, characterization, antibacterial, antidiabetic, and anticholinergic potentials. Bioorg. Chem. 2019, 88, 102931. [Google Scholar] [CrossRef]
  62. Cetin Cakmak, K.; Gulcin, I. Anticholinergic and antioxidant activities of usnic acid-An activity-structure insight. Toxicol. Rep. 2019, 6, 1273–1280. [Google Scholar] [CrossRef] [PubMed]
  63. Polat Kose, L.; Gulcin, I.; Goren, A.C.; Namiesnik, J.; Martinez-Ayala, A.L.; Gorinstein, S. LC-MS/MS analysis, antioxidant and anticholinergic properties of galanga (Alpinia officinarum Hance) rhizomes. Ind. Crops Prod. 2015, 74, 712–721. [Google Scholar] [CrossRef]
  64. Gulcin, I.; Tel, A.Z.; Goren, A.C.; Taslimi, P.; Alwasel, S. Sage (Salvia pilifera): Determination its polyphenol contents, anticholinergic, antidiabetic and antioxidant activities. J. Food Meas. Charact. 2019, 13, 2062–2074. [Google Scholar] [CrossRef]
  65. Gulcin, I.; Taslimi, P.; Aygün, A.; Sadeghian, N.; Bastem, E.; Kufrevioglu, O.I.; Turkan, F.; Şen, F. Antidiabetic and antiparasitic potentials: Inhibition effects of some natural antioxidant compounds on α-glycosidase, α-amylase and human glutathione S-transferase enzymes. Int. J. Biol. Macromol. 2018, 119, 741–746. [Google Scholar] [CrossRef]
  66. Bytyqi-Damoni, A.; Kestane, A.; Taslimi, P.; Tüzün, B.; Zengin, M.; Genç Bilgicli, H.; Gulcin, I. Novel carvacrol based new oxypropanolamine derivatives: Design, synthesis, characterization, biological evaluation, and molecular docking studies. J. Mol. Struct. 2020, 1202, 127297. [Google Scholar] [CrossRef]
  67. Biçer, A.; Kaya, R.; Yakali, G.; Gultekin, M.S.; Turgut Cin, G.; Gulcin, I. Synthesis of novel β-amino carbonyl derivatives and their inhibition effects on some metabolic enzymes. J. Mol. Struct. 2020, 1204, 127453. [Google Scholar]
  68. Eruygur, N.; Atas, M.; Tekin, M.; Taslimi, P.; Kocyigit, U.M.; Gulcin, I. In vitro antioxidant, antimicrobial, anticholinesterase and antidiabetic activities of Turkish endemic Achillea cucullata (Asteraceae) from ethanol extract. S. Afr. J. Bot. 2019, 120, 141–145. [Google Scholar] [CrossRef]
  69. Oztaskin, N.; Kaya, R.; Maras, A.; Sahin, E.; Gulcin, I.; Goksu, S. Synthesis and characterization of novel bromophenols: Determination of their anticholinergic, antidiabetic and antioxidant activities. Bioorg. Chem. 2019, 87, 91–102. [Google Scholar] [CrossRef]
Crystals 10 00171 sch001 550
Scheme 1. Synthesis of the hydroxyethyl-substituted Ag-NHC complex 1.
Scheme 1. Synthesis of the hydroxyethyl-substituted Ag-NHC complex 1.
Crystals 10 00171 sch001
Crystals 10 00171 g001 550
Figure 1. The 1H NMR data for the hydroxyethyl-substituted Ag-NHC complex 1.
Figure 1. The 1H NMR data for the hydroxyethyl-substituted Ag-NHC complex 1.
Crystals 10 00171 g001
Crystals 10 00171 g002 550
Figure 2. The 13C NMR data for the hydroxyethyl-substituted Ag-NHC complex 1.
Figure 2. The 13C NMR data for the hydroxyethyl-substituted Ag-NHC complex 1.
Crystals 10 00171 g002
Crystals 10 00171 g003 550
Figure 3. The FTIR spectrum of the hydroxyethyl-substituted Ag-NHC complex 1.
Figure 3. The FTIR spectrum of the hydroxyethyl-substituted Ag-NHC complex 1.
Crystals 10 00171 g003
Crystals 10 00171 g004 550
Figure 4. The UV-Vis spectrum of the hydroxyethyl-substituted Ag-NHC complex 1.
Figure 4. The UV-Vis spectrum of the hydroxyethyl-substituted Ag-NHC complex 1.
Crystals 10 00171 g004
Crystals 10 00171 g005 550
Figure 5. Molecular structure of Ag-NHC complex 1 with ellipsoids drawn at 30% probability level. Selected bond lengths (Å) and angles (°): Ag1–Ag2 3.0966(7), Ag1–C1 2.098(7), Ag1–C12 2.096(8), Ag2–Br1 2.4277(14); Ag1–Ag2–Br1 86.39(3), C1–Ag1–C12 171.1(3), C1–Ag1–Ag2 93.0(2), C12–Ag1–Ag2 95.6(2), C1–N1–C10 125.4(7), N1–C10–C11 115.5(9), C1–N2–C2 125.3(7), N2–C2–C3 111.9(10), C10–C11–O2A 112.6(14), C10–C11–O2B 116.2(17), C12–N3–C13 124.6(7), N3–C13–C14 112.9(8), C12–N4–C21 125.2(8), N4–C21–C22 111.0(9), C21–C22–O1 107.3(14). [Symmetry code: (*) 1 − x, 1 − y, 1 − z].
Figure 5. Molecular structure of Ag-NHC complex 1 with ellipsoids drawn at 30% probability level. Selected bond lengths (Å) and angles (°): Ag1–Ag2 3.0966(7), Ag1–C1 2.098(7), Ag1–C12 2.096(8), Ag2–Br1 2.4277(14); Ag1–Ag2–Br1 86.39(3), C1–Ag1–C12 171.1(3), C1–Ag1–Ag2 93.0(2), C12–Ag1–Ag2 95.6(2), C1–N1–C10 125.4(7), N1–C10–C11 115.5(9), C1–N2–C2 125.3(7), N2–C2–C3 111.9(10), C10–C11–O2A 112.6(14), C10–C11–O2B 116.2(17), C12–N3–C13 124.6(7), N3–C13–C14 112.9(8), C12–N4–C21 125.2(8), N4–C21–C22 111.0(9), C21–C22–O1 107.3(14). [Symmetry code: (*) 1 − x, 1 − y, 1 − z].
Crystals 10 00171 g005
Crystals 10 00171 g006 550
Figure 6. Representation of the packing diagram for the Ag-NHC complex 1. The Ag2 atoms settle in each corner of the unit cell and one is in the middle, while the bromide anions are between these corner silver atoms. The Ag, Br and O atoms are shown as balls, while the other atoms are shown in a wireframe style. For the sake of clarity, hydrogen atoms that do not to play role in the bonding are omitted.
Figure 6. Representation of the packing diagram for the Ag-NHC complex 1. The Ag2 atoms settle in each corner of the unit cell and one is in the middle, while the bromide anions are between these corner silver atoms. The Ag, Br and O atoms are shown as balls, while the other atoms are shown in a wireframe style. For the sake of clarity, hydrogen atoms that do not to play role in the bonding are omitted.
Crystals 10 00171 g006
Table
Table 1. Crystal data and experimental details for the Ag-NHC complex 1.
Table 1. Crystal data and experimental details for the Ag-NHC complex 1.
Crystal DataExperimental Details
Empirical FormulaC44H56Ag3Br3N8O4
Formula Weight1324.30
Temperature (K)293(2)
Crystal System, space groupMonoclinic, P21/n
a, b, c (Å)10.7530(6), 13.2516(10), 17.8818(11)
α, β, γ (⁰)90, 106.473(6), 90
V (Å3)2443.5(3)
Z2
Density (calculated) (g/cm3) 1.800
Absorption coefficient (µ, mm−1)3.692
F(000)1308
Crystal size (mm3)0.386 × 0.342 × 0.178
RadiationMoKα (λ = 0.71073)
2θ range for data collection (°)6.002 to 51.358
Index ranges−6 ≤ h ≤ 13, −16 ≤ k ≤ 7, −21 ≤ l ≤ 21
Reflections collected8043
Independent reflections4589 [Rint = 0.027, Rsigma = 0.055]
Restraints/Parameters8/269
Goodness-of-fit on F21.034
Final R indices [I ≥ 2σ (I)]R1 = 0.074, wR2 = 0.208
R indicesR1 = 0.113, wR2 = 0.237
Table
Table 2. The enzyme inhibition results (IC50 and Ki values) of Ag-NHC complex 1 against hCA I, hCA II, α-Glycosidase, AChE, and BChE enzymes.
Table 2. The enzyme inhibition results (IC50 and Ki values) of Ag-NHC complex 1 against hCA I, hCA II, α-Glycosidase, AChE, and BChE enzymes.
CompoundsIC50 (µM)Ki (µM)
hCA Ir2hCA IIr2AChEr2BChEr2α-Glyr2hCA IhCA IIAChEBChEα-Gly
Complex 10.930.97861.260.943536.410.974550.250.97908.110.92521.14 ± 0.261.88 ± 0.2025.32 ± 3.7641.31 ± 7.4210.75 ± 2.47
AZA *54.880.988048.220.9878------50.17 ± 4.1742.15 ± 8.11---
Tacrine **----76.20.987496.40.9424----47.18 ± 8.3769.08 ± 13.40-
Acarbose ***--------22.80-----12.60 ± 0.7
* AZA (acetazolamide) was used as a positive control for human carbonic anhydrase I and II isoforms (hCA I and II). ** TAC (tacrine) was used as a positive control for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. *** Acarbose was used as a positive control for α-glycosidase enzyme [40].

Share and Cite

MDPI and ACS Style

Aktas, A.; Barut Celepci, D.; Gok, Y.; Taslimi, P.; Akincioglu, H.; Gulcin, İ. A Novel Ag-N-Heterocyclic Carbene Complex Bearing the Hydroxyethyl Ligand: Synthesis, Characterization, Crystal and Spectral Structures and Bioactivity Properties. Crystals 2020, 10, 171. https://0-doi-org.brum.beds.ac.uk/10.3390/cryst10030171

AMA Style

Aktas A, Barut Celepci D, Gok Y, Taslimi P, Akincioglu H, Gulcin İ. A Novel Ag-N-Heterocyclic Carbene Complex Bearing the Hydroxyethyl Ligand: Synthesis, Characterization, Crystal and Spectral Structures and Bioactivity Properties. Crystals. 2020; 10(3):171. https://0-doi-org.brum.beds.ac.uk/10.3390/cryst10030171

Chicago/Turabian Style

Aktas, Aydin, Duygu Barut Celepci, Yetkin Gok, Parham Taslimi, Hulya Akincioglu, and İlhami Gulcin. 2020. "A Novel Ag-N-Heterocyclic Carbene Complex Bearing the Hydroxyethyl Ligand: Synthesis, Characterization, Crystal and Spectral Structures and Bioactivity Properties" Crystals 10, no. 3: 171. https://0-doi-org.brum.beds.ac.uk/10.3390/cryst10030171

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop