PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of bioinorgchemapplBioinorganic Chemistry and Applications
 
Bioinorg Chem Appl. 2017; 2017: 7895023.
Published online 2017 February 19. doi:  10.1155/2017/7895023
PMCID: PMC5337788

X-Ray Crystallographic Analysis, EPR Studies, and Computational Calculations of a Cu(II) Tetramic Acid Complex

Abstract

In this work we present a structural and spectroscopic analysis of a copper(II) N-acetyl-5-arylidene tetramic acid by using both experimental and computational techniques. The crystal structure of the Cu(II) complex was determined by single crystal X-ray diffraction and shows that the copper ion lies on a centre of symmetry, with each ligand ion coordinated to two copper ions, forming a 2D sheet. Moreover, the EPR spectroscopic properties of the Cu(II) tetramic acid complex were also explored and discussed. Finally, a computational approach was performed in order to obtain a detailed and precise insight of product structures and properties. It is hoped that this study can enrich the field of functional supramolecular systems, giving place to the formation of coordination-driven self-assembly architectures.

1. Introduction

Tetramic acid derivatives (pyrrolidine-2,4-diones) constitute a unique class of nitrogen five-membered heterocyclic compounds that have attracted significant attention over the years due to their occurrence in naturally bioactive materials. They present various pharmaceutical and biological activities including antibiotic, cytotoxic, antifungal, and anti-HIV activities [15]. Representative biologically active natural products containing the 2,4-pyrrolidinedione system include tenuazonic acid (Scheme 1) [6, 7], reutericyclin (Scheme 2) with a wide range of pharmacological activities [810], the HIV integrace inhibitor equisetin and the tetramic acid-homologues possessing the unsaturated decalin ring system [11], the antibiotic “Magnesidine” (Scheme 3) containing the 5-ethylidene and 3-alkanoyl substitutes with Mg(II) [12, 13], harzianic acid, showing Iron (III)-binding affinity [14, 15], penicillenols (Scheme 4) [16, 17], epicoccamides [18], streptolydigin which inhibits RNA polymerase [19, 20], and the melophlin family of compounds which have shown antimicrobial activity [21].

The 3-acyl substituted tetramic rings provide metal binding capacity [22, 23], and this system has been primarily investigated in the fungal metabolite tenuazonic acid which has shown to form complexes with Ca(II) and Mg(II) [24]. Recently, the naturally occurring “chaunolidines A–C” tetramic acid analogues, isolated from an Australian marine-derived fungus, were shown to form metal chelates with Fe(III), Au(II), Cu(II), Mg(II), and Zn(II) [25]. Melophlin, a member of N-methyl-3-acetyl tetramic acid, chelates with Mg, Zn, Ga, La, and Ru ions [21, 26]. Biological evaluation of the complexes shows antiproliferative activity against various cancer cells. Additionally, more complexes of naturally derived tetramic acids have been reported, the most important being those of decylidene tetramic acid (C12-TA), a degradation product derived from 3-oxododecanoyl homoserine lactone (3-oxo-C12-HSL) that binds essential metals such as Fe(III) and Ga(III) ions [27]. Recently, a new synthetic methodology on tetramic acid core and subsequent organocesium carbanionic architectures has been explored [28]. Likewise, the synthesis of chelating agents containing the oxygen equivalent 3-acyltetronic acid scaffolds has been extensively studied [29].

Construction of densely functionalized 3-acyltetramic acids is a topic of continuing interest. The development of effective synthetic methodologies and theoretical investigations on the tautomerism of these compounds have been the focus of many researchers [3032].

Our research group has contributed notably to the synthesis and study of five-membered β,β′-tricarbonyl oxygen and nitrogen heterocycles and their coordination compounds. The β,β′-tricarbonyl compounds form a diverse class of ligands with many applications in inorganic chemistry. The 3-acylated tetramic acids (heterocyclic core), in their deprotonated form, act as ligands for the synthesis of coordination compounds. The 5-arylidene-3-alkanoyl tetramic acids contain structural adjuncts, an enolic β,β′-tricarbonyl moiety, a lipophilic 3-alkanoyl moiety, and a hydrophobic group at the 5-position anticipated to permit versatile activity. The ability of N-acetyl-tetramic acids as chelating monoanions prompted us to investigate the synthesis of rhodium(I) [33], cationic diammineplatinum(II) complexes [34], and palladium (II) complexes [35]. Additionally, we have investigated the coordination ability of tetramic acids with transition metal ions such as copper(II) nickel(II), cobalt(II), and zinc(II) [36]. Here, our interest has been focused on the further study on the recently presented copper(II) and zinc(II) complexes of N-acetyl-5-arylidene tetramic acid [37].

Copper(II) ion has been found in many supramolecular features [38] and metalloproteins [39]. Copper and its compounds have many medical applications. Copper(II) complexes have been used as analgetic, antipyretic, anti-inflammatory, and platelet antiaggregating agents. They have antioxidant activity and protect against the consequences of UV exposure. Binuclear complexes like Cu2(asp)4  {asp = aspirinate} exert additional activities, including antiulcer, anticancer, antimutagenic, and antimicrobial effects [40]. Copper(II) complexes may have less severe side effects and may overcome acquired and inherited resistance to medicines based on platinum(II) [41, 42].

Recently, it has been reported that copper (II) complexes incorporating ligands with appended functional groups can be used in early AD (Alzheimer Disease) pathology by PET (position emission tomography). Clinical studies for Cu(II) complexes with a functionalized styrylpyridine group indicate binding to amyloid-β plaques and effectively crossing of the blood-brain barriers [43]. Consequently, transition metals, such as Cu and Zn, have a suggested link to AD pathology.

In this report we present the crystal structure and EPR spectroscopic properties of the copper(II) complex. Computational calculations on the complex were also performed in order to obtain a detailed and precise insight into the structure and properties of the complex.

2. Experimental Section

2.1. Materials and Methods

The ligand, 3-acetyl-5-benzylidene-tetramic acid, and the copper (II) complex were prepared according to our previous publication [37].

2.2. Synthesis of [Cu(TA-H+)2(EtOH)2]

To a solution of 3-acetyl -5-benzylidene tetramic acid (TA) (1.1 mmoL) in the minimum amount of ethanol was added Cu(CH3COO)2·H2O (0.55 mmoL), dissolved in the minimum amount of ethanol, and the resulting solution was refluxed under stirring for 2 hours. The reaction mixture was left to cool at rt, and the precipitate was filtered, washed with ethanol, and dried to give a pale green solid (374 mg, 98%), mp 173°C (dec), λmax (CHCl3)/nm 341 (log ε 4.46) and 642 (2.51), νmax/cm−1 3520 (s), 1740 (s), 1690, 1590 (s), 1490 (s), 1370, 490 (w), HRMS: calcd for C30H25N2O8Cu 604.0908; found 604.0807.

2.3. X-Ray Crystallography

Crystals of [Cu(TA-H+)2]·2EtOH suitable for X-ray crystallography were obtained from a solution of ethanol diffused with diethyl ether.

The data were collected at 150(2) K on a Bruker-Nonius Apex II CCD diffractometer using MoKα radiation (λ = 0.71073 Å) and were corrected for Lorentz-polarization effects and absorption. The structure was solved by direct methods and refined on F2 using all the reflections [44] All the nonhydrogen atoms were refined using anisotropic atomic displacement parameters and hydrogen atoms were inserted at calculated positions using a riding model. Crystal data, data collection, and structure refinement details are summarised in Table 1. “CCDC nnnnnnn contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via https://www.ccdc.cam.ac.uk/structures-beta/.”

Table 1
Crystal data.

2.4. EPR Spectroscopy

CW EPR measurements at Q-band were carried out on a home-assembled spectrometer equipped with an ER 5106 QT Bruker resonator. Simulations of the spectra were performed with the SpinCount software kindly provided to us by Professor Michael Hendrich, Carnegie Mellon University, Pittsburgh, PA, USA.

2.5. Computational Methods and Details

Density functional theoretical methodology was selected for the calculation of the structural details of the tetramic acid (ligand) and metal complexes' structural models shown in Figures Figures44 and and55 and Table 3. The B3LYP [4547], the most widely used of all the functionals, was employed as implemented in the GAUSSIAN 09 program package [48].

Figure 4
Ball and stick draws of the optimized structures: (a) N-acetyl-3-acetyl-5-arylidenetetramic acid (TA) and (b) copper(II) complex [Cu(TA-H+)2(EtOH)2]. In Figure (b) hydrogen atoms have been omitted for clarification. Main bond lengths and atoms' number ...
Figure 5
Atomic charges calculated by natural population analysis at B3LYP/TZVP level of theory of (a) N-acetyl-3-acetyl-5-arylidenetetramic anion (TA-H+) and (b) copper(II) complex (only a part of the structure is presented here). “Mean” charges ...
Table 3
Bond lengths in Angstroms of tetramic acid (TA) and Cu, Zn-complexes (Cu(TA-H+)2(EtOH)2), (Zn(TA-H+)2(EtOH)2) calculated by B3LYP method using the TZVP basis set. Atoms numbering refers to Figure 4.

The accuracy and good performance of the computational methods and basis sets, which are chosen for the investigated systems, have been tested by comparing the calculated properties with experimental structural data that are available in the literature [37].

The electronic structures of the atoms participating in the investigated structures are described by the Ahlrichs triple zeta TZVP basis sets included in definition polarization Gaussian-type functions (GTF) [49, 50]. The geometries of the structural models of the ligand and the complexes have been fully optimized at the B3LYP/TZVP level of theory using the Berny algorithm as implemented in Gaussian 09 program package. All optimized geometries correspond to stationary points on the potential energy surface, as no imaginary frequencies have been obtained.

The calculation of natural atomic charges was performed with the natural bond orbital, NBO 3.1 program [51] on optimized geometries at B3LYP level of theory with the TZVP basis set.

3. Results and Discussion

3.1. Structure of [Cu(TA-H+)2·2EtOH]

The copper ion lies on a centre of symmetry (Figure 1), so the asymmetric unit comprises one ligand molecule, one ethanol solvate molecule, and half of a copper(II) ion. The geometry at the metal ion is tetragonal; the copper ion is coordinated to two bidentate (TA-H+) anions in the basal plane and, via longer apical bonds (2.522 (4) Å), to the amide oxygen atoms of two neighbouring complexes. Each ligand ion is therefore coordinated to two copper ions, forming a 2D sheet lying perpendicular to the a-axis (Figure 2). There are no notable interactions between the sheets.

Figure 1
Perspective view of the complex showing 50% probability ellipsoids. Suffixes on the atom labels indicate atoms generated using the following symmetry operations: A, −x, 2 − y, −z; B, −x, 1/2 + y, 1/2 − z; C, x, ...
Figure 2
Part of the polymeric sheet structure parallel to the a-axis. Hydrogen bonds shown as dashed lines; hydrogen atoms omitted for clarity.

The ethanol solvate molecules are hydrogen bonded to one of the oxygen donors in the square plane (O5–H5(...)O2; 3.010 (6) Å under symmetry operation x, −y + 3/2, z + 1/2) and have a longer interaction with the other (O5–H5(...)O3; 3.213 (6) Å under −x, y − 1/2, –z + 1/2). The mean plane of the ligand amide group makes an angle of 35.3 (2)° with the mean plane of the five-membered ring. Selected bond lengths and angles are given in Table 2.

Table 2
Selected bond lengths (Å) and angles (°).

3.2. EPR Spectroscopy

The EPR (Figure 3) shows the Q-band EPR spectrum from a frozen solution of Cu(II) complex in chloroform recorded at 100 K. The spectrum consists of a typical axial Cu2+ signal with g|| > g[perpendicular]. The g|| component splits further into four lines due to hyperfine interactions with the 63/65Cu (I = 3/2) nucleus. Simulation of the spectrum yields g|| = 2.33, g[perpendicular] = 2.07, and A|| = 490 MHz. The values of g|| and A|| are in line with the unpaired electron being in dx2 y 2 orbital and the equatorial coordination mode of “4 Oxygens” [52] in agreement with the crystal structure.

Figure 3
Experimental (black line) and theoretical (red line) Q-band EPR spectra from a frozen chloroform solution of Cu(II) complex. The inset focuses on the g|| part of the spectrum. EPR conditions: temperature, 100 K; modulation amplitude, 5 Gpp; ...

3.3. Computational Methods

3.3.1. Calculated Structural Details

The gas phase ligand molecule of tetramic acid (Figure 4(a)) is not planar as the calculated dihedral angle between the phenyl and pyrrole ring is about 31°, in accordance with the crystalline structure where there is a twist of 27.42 (8)° between the mean planes of the two rings. The centrosymmetric Cu(II)-complex (point group: Ci), as presented in Figure 4(b), consists of two tetramic acid anions which act as bidentate ligands located in equatorial positions around the central metal. The two ligands are coordinated to the central metal via carbonyl oxygen bridges. The two –C=O– bonds are almost identical characterized by bond length of 1.259 Å (Table 3). The calculated dihedral angle between phenyl and pyrrole rings is about 25° which is in excellent agreement with the corresponding experimental value of the crystalline structure 25.13°.

Four oxygen atoms are positioned near the copper atom disposed in an almost square planar geometry. The two groups of diagonal oxygens have slightly different –O–Cu– bond distances, assuming values of 1.979 and 1.994 Å. In order to describe more realistically the solid state structure, two ethanol molecules were placed at axial positions. Therefore, the metal coordination sphere is completed by these two oxygen atoms from ethanol molecules in transpositions having a longer –O–Cu– distance, that is, 2.469 Å. The 2-3% variation between the calculated and crystallographic Cu-donor distances could be attributed to (i) the approximations adopted for the current structural model as two ethanol molecules have been placed in axial positions of the structural model instead of two other complexes mutually (up and down) arranged around the central complex in crystal's unit, (ii) crystal packing effects, and (iii) the theoretical level and basis set limitations of the calculations.

As expected there is an elongation of –C=O bond length upon complexation to the metal ion from 1.225 and 1.228 Å calculated for the ligand anion to 1.259 and 1.260 Å, for the copper and zinc complexes, respectively. These bonds have been measured at 1.268 and 1.253 Å [37] for copper and zinc complexes being very close to our calculations.

For comparison, in Table 3 equivalent crystallographic data for tetramic acid (TA) ligand and Zn(TA-H+)2·2EtOH (Scheme 5) are displayed [37], as well as selected calculated structural data at the B3LYP/TZVP level of theory.

3.3.2. NBO Analysis

Special attention was paid to donor-acceptor effects between ligand and metal. For this, natural bond orbital (NBO) theory and simulation have been applied [5355]. The calculated natural atomic charges are presented in Figures 5(a) and 5(b) for the tetramic acid anion and the Cu-complex. Based on the calculated atomic charges we can estimate the “mean” charge of various groups (Figures 5(a) and 5(b)). Comparing the “mean” charge of various groups between the free anion and the complex it is revealed that a net electron density shift takes place towards the location of the Cu ion, which undergoes the greatest charge variation from +2 to +1.097.

Finally the binding energy for the Cu-complex has been calculated from the total energies of the optimized structures of the specific isolated species as

EbindEcomplexECu2+2Eligandanion2Eethanol=3820.4932271639.48149932x934.88839322x155.104142=1.0266573Eh.
(1)

3.3.3. Bond/Atom Valence Calculation

In bond-valence theory Sij, the valence of the AjXj bond with the length Rij is calculated via the following basic equation: Sij = e[(r0Rij)/b], where r0 and b are empirically determined bond-valence parameters for a given cation-anion pair A, X [56]. According to this theory the atom valence SCu =  Σ(Sij).

In this study we used for [Cu–O pair] the parameters r0 = 1.679 and b = 0.36 [57].

The results are tabulated in Table 4.

Table 4
Bond and copper valence data for Cu-complex.

4. Conclusions

In the present work we report a detailed investigation of a new Cu(II) complex involving the 3-acetyl-tetramic acid as “model ligand.” The structure and the “supramolecular” arrangement of the isolated complex have been investigated by single crystal X-ray crystallography. In addition, we have more completely characterized the complex with a combination of EPR studies and computational calculations. The consistency between theoretical and experimental values is good in general.

The 3-acetyl-tetramate ligand, functionalized with the 5-benzylidene group, has been used to prepare with Cu(OCOCH3)2·2H2O in ethanol, the complex copper (II) N-acetyl-5-benzylidene tetramic acid [Cu(TA-H+)2·2EtOH]. Each ligand ion is coordinated to two copper ions, forming a polymeric 2D sheet lying perpendicular to the α-axis, without notable interactions between the sheets. This model is a promising system for the development of “metallosupramolecular” architectures.

Work in progress includes the design of novel synthetic crystalline “organic linkers” to construct coordination-driven self-assembly architectures.

Acknowledgments

Financial support from the National Technical University of Athens for research related to this article is gratefully acknowledged. The authors are grateful to the Science and Technology Facilities Council for access to the SRS at Daresbury, UK. J. Markopoulos would like to thank Mr. Andrew Kourmoulis for his skillful technical assistance provided to him.

Competing Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

References

1. Royles B. J. L. Naturally occurring tetramic acids: structure, isolation, and synthesis. Chemical Reviews. 1995;95(6):1981–2001. doi: 10.1021/cr00038a009. [Cross Ref]
2. Athanasellis G., Igglessi-Markopoulou O., Markopoulos J. Tetramic and tetronic acids as scaffolds in bioinorganic and bioorganic chemistry. Bioinorganic Chemistry and Applications. 2010;2010:11. doi: 10.1155/2010/315056.315056 [PMC free article] [PubMed] [Cross Ref]
3. Schobert R., Schlenk A. Tetramic and tetronic acids: an update on new derivatives and biological aspects. Bioorganic and Medicinal Chemistry. 2008;16(8):4203–4221. doi: 10.1016/j.bmc.2008.02.069. [PubMed] [Cross Ref]
4. Jeong Y.-C., Bikadi Z., Hazai E., Moloney M. G. A detailed study of antibacterial 3-acyltetramic acids and 3-acylpiperidine-2,4-diones. ChemMedChem. 2014;9(8):1826–1837. doi: 10.1002/cmdc.201402093. [PubMed] [Cross Ref]
5. Jeong Y.-C., Anwar M., Bikadi Z., Hazai E., Moloney M. G. Natural product inspired antibacterial tetramic acid libraries with dual enzyme inhibition. Chemical Science. 2013;4(3):1008–1015. doi: 10.1039/c2sc21713a. [Cross Ref]
6. Rosett T., Sankhala R. H., Stickings C. E., Taylor M. E. U., Thomas R. Studies in the biochemistry of micro-organisms. 103. Metabolites of Alternaria tenuis Auct.: culture filtrate products. Biochemical Journal. 1957;67(3):390–400. [PubMed]
7. Schobert R., Jagusch C., Melanophy C., Mullen G. Synthesis and reactions of polymer-bound Ph3P=C=C=O: a quick route to tenuazonic acid and other optically pure 5-substituted tetramates. Organic and Biomolecular Chemistry. 2004;2(23):3524–3529. doi: 10.1039/b412779j. [PubMed] [Cross Ref]
8. Höltzel A., Gänzle M. G., Nicholson G. J., Hammes W. P., Jung G. The first low molecular weight antibiotic from lactic acid bacteria: reutericyclin, a new tetramic acid. Angewandte Chemie—International Edition. 2000;39(15):2766–2768. doi: 10.1002/1521-3773(20000804)39:15<2766::aid-anie2766>3.0.co;2-g. [PubMed] [Cross Ref]
9. Jeong Y.-C., Moloney M. G. Tetramic acids as scaffolds: synthesis, tautomeric and antibacterial behaviour. Synlett. 2009;(15):2487–2491. doi: 10.1055/s-0029-1217745. [Cross Ref]
10. Gänzle M. G. Reutericyclin: biological activity, mode of action, and potential applications. Applied Microbiology and Biotechnology. 2004;64(3):326–332. doi: 10.1007/s00253-003-1536-8. [PubMed] [Cross Ref]
11. Healy A. R., Westwood N. J. Synthetic studies on the bioactive tetramic acid JBIR-22 using a late stage Diels-Alder reaction. Organic and Biomolecular Chemistry. 2015;13(42):10527–10531. doi: 10.1039/c5ob01771h. [PubMed] [Cross Ref]
12. Langer P., Döring M., Schreiner P. R., Görls H. Synthesis of radialene-shaped pyrroles by multiple-anion-capture reactions of 1,3-dianions. Chemistry. 2001;7(12):2617–2627. doi: 10.1002/1521-3765(20010618)7:12<2617::aid-chem26170>3.0.co;2-f. [PubMed] [Cross Ref]
13. Kohl H., Bhat S. V., Patell J. R., et al. Structure of magnisidin, a new magnesium-containing antibiotic from pseudomonas magnesiorubra. Tetrahedron Letters. 1974;15(12):983–986. doi: 10.1016/S0040-4039(01)82385-6. [Cross Ref]
14. Vinale F., Nigro M., Sivasithamparam K., et al. Harzianic acid: a novel siderophore from Trichoderma harzianum. FEMS Microbiology Letters. 2013;347(2):123–129. doi: 10.1111/1574-6968.12231. [PubMed] [Cross Ref]
15. Healy A. R., Izumikawa M., Slawin A. M. Z., Shin-Ya K., Westwood N. J. Stereochemical assignment of the protein-protein interaction inhibitor JBIR-22 by total synthesis. Angewandte Chemie—International Edition. 2015;54(13):4046–4050. doi: 10.1002/anie.201411141. [PMC free article] [PubMed] [Cross Ref]
16. Kempf K., Raja A., Sasse F., Schobert R. Synthesis of penicillenol C1 and of a bis-azide analogue for photoaffinity labeling. Journal of Organic Chemistry. 2013;78(6):2455–2461. doi: 10.1021/jo3026737. [PubMed] [Cross Ref]
17. Kempf K., Schmitt F., Bilitewski U., Schobert R. Synthesis, stereochemical assignment, and bioactivity of the Penicillium metabolites penicillenols B1 and B2. Tetrahedron. 2015;71(31):5064–5068. doi: 10.1016/j.tet.2015.05.116. [Cross Ref]
18. Loscher S., Schobert R. Total synthesis and absolute configuration of epicoccamide D, a naturally occurring mannosylated 3-acyltetramic acid. Chemistry—A European Journal. 2013;19(32):10619–10624. doi: 10.1002/chem.201301914. [PubMed] [Cross Ref]
19. Rinehart K. L., Jr., Beck J. R., Epstein W. W., Spicer L. D. Streptolydigin. I. Streptolic acid. Journal of the American Chemical Society. 1963;85(24):4035–4037. doi: 10.1021/ja00907a032. [Cross Ref]
20. Pronin S. V., Martinez A., Kuznedelov K., Severinov K., Shuman H. A., Kozmin S. A. Chemical synthesis enables biochemical and antibacterial evaluation of streptolydigin antibiotics. Journal of the American Chemical Society. 2011;133(31):12172–12184. doi: 10.1021/ja2041964. [PMC free article] [PubMed] [Cross Ref]
21. Biersack B., Diestel R., Jagusch C., Sasse F., Schobert R. Metal complexes of natural melophlins and their cytotoxic and antibiotic activities. Journal of Inorganic Biochemistry. 2009;103(1):72–76. doi: 10.1016/j.jinorgbio.2008.09.005. [PubMed] [Cross Ref]
22. Romano A. A., Hahn T., Davis N., et al. The Fe(III) and Ga(III) coordination chemistry of 3-(1-hydroxymethylidene) and 3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione: novel tetramic acid degradation products of homoserine lactone bacterial quorum sensing molecules. Journal of Inorganic Biochemistry. 2012;107(1):96–103. doi: 10.1016/j.jinorgbio.2011.10.009. [PMC free article] [PubMed] [Cross Ref]
23. Zaghouani M., Nay B. 3-acylated tetramic and tetronic acids as natural metal binders: myth or reality? Natural Product Reports. 2016;33(4):540–548. doi: 10.1039/c5np00144g. [PubMed] [Cross Ref]
24. Steyn P. S., Rabie C. J. Characterization of magnesium and calcium tenuazonate from Phoma sorghina. Phytochemistry. 1976;15(12):1977–1979. doi: 10.1016/S0031-9422(00)88860-3. [Cross Ref]
25. Shang Z., Li L., Espósito B. P., et al. New PKS-NRPS tetramic acids and pyridinone from an Australian marine-derived fungus, Chaunopycnis sp. Organic and Biomolecular Chemistry. 2015;13(28):7795–7802. doi: 10.1039/c5ob01058f. [PubMed] [Cross Ref]
26. Aoki S., Higuchi K., Ye Y., Satari R., Kobayashi M. Melophlins A and B, novel tetramic acids reversing the phenotype of ras- transformed cells, from the marine sponge Melophlus sarassinorum. Tetrahedron. 2000;56(13):1833–1836. doi: 10.1016/S0040-4020(00)00092-2. [Cross Ref]
27. Kaufmann G. F., Sartorio R., Lee S.-H., et al. Revisiting quorum sensing: discovery of additional chemical and biological functions for 3-oxo-N-acylhomoserine lactones. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(2):309–314. doi: 10.1073/pnas.0408639102. [PubMed] [Cross Ref]
28. Martinez-Ariza G., Ayaz M., Roberts S. A., Rabanal-Leõn W. A., Arratia-Pérez R., Hulme C. The synthesis of stable, complex organocesium tetramic acids through the Ugi reaction and cesium-carbonate-promoted cascades. Angewandte Chemie—International Edition. 2015;54(40):11672–11676. doi: 10.1002/anie.201504377. [PubMed] [Cross Ref]
29. Rouleau J., Korovitch A., Lion C., et al. Synthesis and evaluation of 3-acyltetronic acid-containing metal complexing agents. Tetrahedron. 2013;69(51):10842–10848. doi: 10.1016/j.tet.2013.10.087. [Cross Ref]
30. Krenk O., Kratochvíl J., Špulák M., et al. Methodology for synthesis of enantiopure 3,5-disubstituted pyrrol-2-ones. European Journal of Organic Chemistry. 2015;2015(24):5414–5423. doi: 10.1002/ejoc.201500620. [Cross Ref]
31. Mikula H., Svatunek D., Skrinjar P., Horkel E., Hametner C., Fröhlich J. DFT study of the Lewis acid mediated synthesis of 3-acyltetramic acids. Journal of Molecular Modeling. 2014;20(5) doi: 10.1007/s00894-014-2181-0. [PubMed] [Cross Ref]
32. Skylaris C.-K., Igglessi-Markopoulou O., Detsi A., Markopoulos J. Density functional and ab initio study of the tautomeric forms of 3-acetyl tetronic and 3-acetyl tetramic acids. Chemical Physics. 2003;293(3):355–363. doi: 10.1016/S0301-0104(03)00359-8. [Cross Ref]
33. Heaton B. T., Jacob C., Markopoulos J., et al. Rhodium(I) complexes containing the enolate of N-acetyl-3-butanoyltetramic acid (Habta) and the crystal structure of [Rh(abta){P(OPh)3}2] Journal of the Chemical Society—Dalton Transactions. 1996;(8):1701–1706.
34. Gavrielatos E., Athanasellis G., Igglessi-Markopoulou O., Markopoulos J. Cationic diamineplatinum(II) complexes containing the enolate of N,3-acetyl-4-hydroxypyrrolin-2-one. Inorganica Chimica Acta. 2003;344:128–132. doi: 10.1016/S0020-1693(02)01317-8. [Cross Ref]
35. Gavrielatos E., Athanasellis G., Heaton B. T., et al. Palladium(II)/β-diketonate complexes containing the enolates of N-acetyl-3-acyltetramic acids: crystal structure of the Lewis base adduct, [Pd(py)4](abta)2. Inorganica Chimica Acta. 2003;351(1):21–26. doi: 10.1016/s0020-1693(03)00196-8. [Cross Ref]
36. Gavrielatos E., Mitsos C., Athanasellis G., et al. Copper(II), cobalt(II), nickel(II) and zinc(II) complexes containing the enolate of N-acetyl-3-butanoyltetramic acid (Habta) and its phenylhydrazone derivative analogues. Crystal structure of [Cu(abta)2(py)2]·2H2O. Journal of the Chemical Society. Dalton Transactions. 2001;(5):639–644.
37. Matiadis D., Igglessi-Markopoulou O., McKee V., Markopoulos J. N-acetyl-5-arylidenetetramic acids: synthesis, X-ray structure elucidation and application to the preparation of zinc(II) and copper(II) complexes. Tetrahedron. 2014;70(14):2439–2443. doi: 10.1016/j.tet.2014.02.019. [Cross Ref]
38. Kounavi K. A., Kitos A. A., Moushi E. E., et al. Supramolecular features in the engineering of 3d metal complexes with phenyl-substituted imidazoles as ligands: the case of copper(II) CrystEngComm. 2015;17(39):7510–7521. doi: 10.1039/c5ce01222h. [Cross Ref]
39. Koval I. A., Van Schilden K. D., Schuitema A. M., et al. Proton NMR spectroscopy and magnetic properties of a solution-stable dicopper(II) complex bearing a single μ-hydroxo bridge. Inorganic Chemistry. 2005;44(12):4372–4382. doi: 10.1021/ic0501770. [PubMed] [Cross Ref]
40. Fujimori T., Yamada S., Yasui H., Sakurai H., In Y., Ishida T. Orally active antioxidative copper(II) aspirinate: synthesis, structure characterization, superoxide scavenging activity, and in vitro and in vivo antioxidative evaluations. Journal of Biological Inorganic Chemistry. 2005;10(8):831–841. doi: 10.1007/s00775-005-0031-3. [PubMed] [Cross Ref]
41. Gracia-Mora I., Ruiz-Ramírez L., Gómez-Ruiz C., et al. Knigth's move in the periodic table, from copper to platinum, novel antitumor mixed chelate copper compounds, casiopeinas, evaluated by an in vitro human and murine cancer cell line panel. Metal-Based Drugs. 2001;8(1):19–28. doi: 10.1155/MBD.2001.19. [PMC free article] [PubMed] [Cross Ref]
42. Almeida J. D. C., Paixão D. A., Marzano I. M., et al. Copper(II) complexes with β-diketones and N-donor heterocyclic ligands: crystal structure, spectral properties, and cytotoxic activity. Polyhedron. 2015;89:1–8. doi: 10.1016/j.poly.2014.12.026. [Cross Ref]
43. Detoma A. S., Krishnamoorthy J., Nam Y., et al. Interaction and reactivity of synthetic aminoisoflavones with metal-free and metal-associated amyloid-β Chemical Science. 2014;5(12):4851–4862. doi: 10.1039/c4sc01531b. [PMC free article] [PubMed] [Cross Ref]
44. Sheldrick G. M. Crystal structure refinement with SHELXL. Acta Crystallographica C. 2015;71:3–8. doi: 10.1107/s2053229614024218. [PMC free article] [PubMed] [Cross Ref]
45. Becke A. D. Density-functional thermochemistry. III. The role of exact exchange. The Journal of Chemical Physics. 1993;98(7):5648–5652. doi: 10.1063/1.464913. [Cross Ref]
46. Stephens P. J., Devlin F. J., Chabalowski C. F., Frisch M. J. Ab Initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields. Journal of Physical Chemistry® 1994;98(45):11623–11627. doi: 10.1021/j100096a001. [Cross Ref]
47. Lee C., Yang W., Parr R. G. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Physical Review B. 1988;37(2):785–789. doi: 10.1103/PhysRevB.37.785. [PubMed] [Cross Ref]
48. Frisch M. J., Trucks G. W., Schlegel H. B., et al. Gaussian 09, Revision A.01. Wallingford, Conn, USA: Gaussian, Inc.; 2009.
49. Schäfer A., Horn H., Ahlrichs R. Fully optimized contracted Gaussian basis sets for atoms Li to Kr. The Journal of Chemical Physics. 1992;97(4):2571–2577. doi: 10.1063/1.463096. [Cross Ref]
50. Schäfer A., Huber C., Ahlrichs R. Fully optimized contracted Gaussian basis sets of triple zeta valence quality for atoms Li to Kr. The Journal of Chemical Physics. 1994;100(8):5829–5835. doi: 10.1063/1.467146. [Cross Ref]
51. Reed A. E., Curtiss L. A., Weinhold F. Intermolecular interactions from a natural bond orbital, donor-acceptor viewpoint. Chemical Reviews. 1988;88(6):899–926. doi: 10.1021/cr00088a005. [Cross Ref]
52. Peisach J., Blumberg W. E. Structural implications derived from the analysis of electron paramagnetic resonance spectra of natural and artificial copper proteins. Archives of Biochemistry and Biophysics. 1974;165(2):691–708. doi: 10.1016/0003-9861(74)90298-7. [PubMed] [Cross Ref]
53. Foster J. P., Weinhold F. Natural hybrid orbitals. Journal of the American Chemical Society. 1980;102(24):7211–7218. doi: 10.1021/ja00544a007. [Cross Ref]
54. Carpenter J. E., Weinhold F. Analysis of the geometry of the hydroxymethyl radical by the ‘different hybrids for different spins’ natural bond orbital procedure. Journal of Molecular Structure: THEOCHEM. 1988;169(C):41–62. doi: 10.1016/0166-1280(88)80248-3. [Cross Ref]
55. Weinhold F., Landis C. R. Discovering Chemistry with Natural Bond Orbitals. Hoboken, NJ, USA: John Wiley & Sons; 2012. [Cross Ref]
56. Brown I. D. The Chemical Bond in Inorganic Chemistry: The Bond Valence Model. Oxford University Press; 2002.
57. Krivovichev S. V. Derivation of bond-valence parameters for some cation-oxygen pairs on the basis of empirical relationships between ro and b. Zeitschrift fur Kristallographie. 2012;227(8):575–579. doi: 10.1524/zkri.2012.1469. [Cross Ref]

Articles from Bioinorganic Chemistry and Applications are provided here courtesy of Hindawi