An integrated experimental and quantum chemical study on the complexation properties of (9′-fluorene)-spiro-5-hydantoin and its thioanalogue

Accepted Manuscript An integrated experimental and quantum chemical study on the complexation properties of (9’-fluorene)-spiro-5-hydantoin and its thioanalogue Anife Ahmedova, Petja Marinova, Marin Marinov, Neyko Stoyanov PII:

S0022-2860(15)30506-8

DOI:

10.1016/j.molstruc.2015.12.018

Reference:

MOLSTR 22051

To appear in:

Journal of Molecular Structure

Received Date: 7 September 2015 Revised Date:

22 October 2015

Accepted Date: 7 December 2015

Please cite this article as: A. Ahmedova, P. Marinova, M. Marinov, N. Stoyanov, An integrated experimental and quantum chemical study on the complexation properties of (9’-fluorene)spiro-5-hydantoin and its thioanalogue, Journal of Molecular Structure (2016), doi: 10.1016/ j.molstruc.2015.12.018. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

An integrated experimental and quantum chemical study on the complexation properties of (9’-fluorene)-spiro-5-hydantoin and its

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thioanalogue

Anife Ahmedova a *, Petja Marinova b, Marin Marinov c, Neyko Stoyanov d

University of Sofia, Department of Analytical Chemistry, Faculty of Chemistry and

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a

Pharmacy, 1, J. Bourchier av., 1164 Sofia, Bulgaria

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University of Plovdiv, Department of General and Inorganic Chemistry with Methodology of Chemistry Education, Faculty of Chemistry, 24, Tzar Assen str., 4000 Plovdiv, Bulgaria, c

Agricultural University – Plovdiv, Department of General Chemistry, Faculty of Plant Protection and Agroecology, 12 "Mendeleev" Blvd, 4000 Plovdiv, Bulgaria

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University of Ruse- Razgrad Branch, Department of Chemistry and Chemical Technology, 47, Aprilsko Vastanie av., 7200 Razgrad, Bulgaria

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d

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b

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ACCEPTED MANUSCRIPT Abstract

The reactivities of (9’-fluorene)-spiro-5-hydantoin and its thio-analogue with Cu(II) were studied in different reaction conditions and the formed products were characterized by

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spectroscopic methods (IR, NMR and/or EPR). It was found that unlike the 2,4-dithioanalogue, both the (9’-fluorene)-spiro-5-hydantoin and its 2-thio derivative form Cu(II) complexes only in presence of a strong base. We identified the coordination mode of the

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ligands and the structure of the complexes through geometry optimization of different models and calculations of the corresponding spectroscopic parameters using ab initio quantum

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chemical methods. The comparison between the experimental and the theoretical data suggested monodentate coordination of the fluorene-hydantoin ligands after deprotonation of one amido group. Additional confirmations of this proposition were obtained from the experimental and DFT-calculated EPR parameters (g-factor and A-tensor), which allowed for

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determination of the most probable geometry of the complexes. We further employed the quantum chemical methods to explain the observed differences in the complexation abilities of variously spiro-5-substituted thio- and dithio- hydantoins, accounting for the structural

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effects on the electron density and acidity of the hydantoin ring.

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Keywords: (9’-fluorene)-spiro-5-hydantoin, thio-hydantoins, Cu(II) complexes, EPR, quantum chemical calculations

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ACCEPTED MANUSCRIPT 1. Introduction

The fluorene unit is frequently employed in the development of various optical devices with potential application as dye-sensitized solar cells [1], polymer light-emitting

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diodes [2-4] and other electroemissive materials [5, 6]. Complexation of fluorene-containing compounds with metal ions is also known as an alternative way to modulate their optical [7, 8] and electrooptical properties [9, 10]. Therefore, extensive research has been devoted to

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proper modulation of their properties either through structural modification of the organic fluorene-bearing molecule or through its coordination with metal ions. On the other hand, the

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hydantoin derivatives are very well known for their physiological activities as antiepileptic drugs [11, 12] or aldose reductase inhibitors [13, 14] to palliate diabetes complications [15, 16]. Examples for compounds exhibiting such biological properties comprise different spiro5-hydantoins that bear either cycloalkane or a fluorene ring [14, 16, 17]. Moreover, the earlier

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suggested anticancer activity of some fluorene-hydantoins [18] has found further confirmation in a recent study including their Pt(II) complexes [19]. Although the coordination ability of hydantoins [20, 21] and spiro-hydantoins [22-25]

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have been studied, the reports on metal complexes of thiohydantoins are limited to the early works of Devilanova et al. [26] and Castan [27, 28] describing various thioamidic

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heterocycles. Exhaustive reviews on the metal complexation by cyclic thionates are given by Raper [29, 30]. The more complicated case of dithiohydantoins that contain two thioamide groups in one 5-membered heterocyclic ring, however, is a challenging task for spectroscopic characterization of their coordination properties and remained relatively unexplored. In spite of the presumably better coordination properties of dithiohydantoins, the only crystal structure of a dithiohydantoin metal complex is the Cu(I) complex of 5,5-dimethyl-2,4-dithiohydantoin, reported by Devilanova [26]. Through combined experimental and quantum chemical studies

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ACCEPTED MANUSCRIPT on metal complexes of some cycloalkane-substituted 2,4-dithiohydantoins we have been able to point out some of the most characteristic spectroscopic fingerprints on the possible coordination modes of dithiohydantoins [31-33]. On the other hand, the complexation reaction of fluorene-substituted 2,4-dithiohydantoins with Cu(II) ions [34] showed stark

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difference with the previously studied cycloalkane-spiro-5-(2,4-dithiohydantoins) [31-33]. Namely, the reaction of the fluorene-spiro-5-(2,4-dithiohydantoin) with Cu(II) does not proceed with its reduction to Cu(I), as in the case of cycloalkane-substituted 2,4-

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dithiohydantoins, but instead, a stable Cu(II) complex was formed under the same synthetic conditions [34]. This was unambiguously confirmed by the well-resolved EPR spectrum

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showing superhyperfine interaction with the coordinated N-atoms from two ligand molecules. Therefore, we decided to estimate the role of the thione-groups in the hydantoin ring and the type of the cyclic substituents at spiro C-atom on the complexation properties of the spirohydantoin ligands. Thereby, we presently focus on the 9’-fluorene-spiro-5-hydantoin and its

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monothio-analogue that have recently been synthesized [35]. The molecular formulas of the studied organic compounds are presented in Fig. 1. The crystal structure of (9’-fluorene)spiro-5-hydantoin (L1) has recently been solved [36] but there is no X-ray data on its thio-

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analogues. Crystal structures of 2-thio- [37] and 2,4-dithiohydantoins [38] are known for a series with cycloalkane substituents at 5th position. There is no X-ray data, however, for any

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metal complex of (9’-fluorene)-spiro-5-hydantoin or its thio-analogues.

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ACCEPTED MANUSCRIPT 8 9

X

7

6

11 12

17

X 5

H

3

4

N

1

N H

2

(CH2)n Y

13

H

16 14

15

n=2;

H

2 Y

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(9’-fluorene)-spiro-5-hydantoin

N 1

3 N

4

5

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cyclopentane-spiro-5-hydantoin (X, Y = O) L1 and its thio-derivatives:

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(X, Y = O) cy5-dioxo and its thio-derivatives:

− 2-thio-hydantoin (X = O; Y = S) L2

− (X = O; Y = S) cy5-2-thio

− 2,4-dithio-hydantoin (X, Y = S) L3

− (X, Y = S)

cy5-dithio

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Figure1. Molecular formula of (9’-fluorene)-spiro-5-hydantoin and the cycloalkane-spiro-5hydantoin, and their thio-analogues along with the atom numbering.

Herein we describe a detailed synthetic, spectroscopic and theoretical study on the

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complexation of 9’-fluorene-spiro-5-hydantoin (L1) and its 2-thio derivative (L2) with Cu(II) in different reaction conditions. The formation of the copper complexes was investigated by

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means of EPR and IR spectroscopy, and supported by quantum chemical calculations for structural elucidation of the complexes. The results are compared with the available data on the complexation properties of spiro-5-dithiohydantoins bearing different substituents at the spiro C-atom [33, 34]. The influence of the fluorene substituent on deprotonation energies and the electron density distribution of various hydantoin derivatives and their thio-analogues (shown in Figure 1), is discussed in regard to the studied complexation with Cu(II).

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ACCEPTED MANUSCRIPT 2. Experimental

2.1. Physical measurements

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IR spectra were recorded on a Perkin-Elmer FTIR-1600 spectrophotometer (KBr pellets). Elemental analyses were performed on a Vario EU III instrument. EPR spectra were recorded on a Bruker B-ER 420 spectrometer at 293 and 77 K using DPPH (2.0036) as

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external standard. The experimental spectra were simulated with a computer program for simulation of powder type EPR spectra for systems with S=1/2 and I≠0 [39]. 1H- and

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C-

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NMR spectra of the ligands were recorded on a Bruker DRX 250 MHz NMR spectrometer in DMSO-d6 used as solvent, and TMS as a standard.

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2.2. Synthesis

All chemicals and solvents were analytical grade reagents and were used as received. Synthesis of (9'-fluorene)-spiro-5-hydantoin (L1): The ligand (L1) (9'-fluorene)-spiro-

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5-hydantoin was obtained following a literature procedure [40] by interaction of fluorenone with sodium cyanide, ammonium carbonate, and ammonium hydroxide in ethanol at 120-125

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°C. The obtained product was recrystallized from tetrahydrofuran/petroleum ether. m.p. 348349 °C. Anal. calcd for C15H10N2O2: C: 71.98; H: 4.03; N: 11.20. Found: C: 71.99; H: 4.32; N: 11.26%. 1H NMR (DMSO-d6) δ,: 7.38-7.94 (m, 8H), 8.61 (s, 1H; N1-H), 11.26 (s, 1H; N3H).

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C NMR (DMSO-d6) δ: 72.8 (C5), 121.2 (arom.), 124.0 (arom.), 128.8 (arom.), 130.3

(arom.), 141.1 (arom.), 143.4 (arom.), 158.1 (C2), 174.6 (C4). Synthesis of (9'-fluorene)-spiro-5-(2-thiohydantoin) (L2): A solution of 4-(2hydroxyethylimino)-(9'-fluorene)-spiro-5-(2-thiohydantoin) [35] (0.70 g; 2.3 mmol) in 8 mL

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ACCEPTED MANUSCRIPT 20 % HCl was refluxed for one hour. After slow cooling for 24 hours the product was obtained as pale yellow crystals that were filtered off and recrystallized from hot water. Yield was 0.5 g (83 %). m.p. 302-303 °C. Anal. calcd. for C15H10N2OS: C: 67.66, H: 3.79, N: 10.53, S: 12.02. Found: C: 67.44, H: 3.89, N: 10.55, S: 12.34. 1H NMR (DMSO-d6) δ: 7.38-7.94 (m, 13

C NMR (DMSO-d6) δ: 74.7 (C5), 120.9

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8H), 10.59 (s, 1H; N1-H), 12.33 (s, 1H; N3-H).

(arom.), 123.7 (arom.), 128.5 (arom.), 130.2 (arom.), 140.7 (arom.), 141.3 (arom.), 174.7 (C2), 183.5 (C4).

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Synthesis of Cu(II)-L1: To the 10 mL of methanol solution of L1 (0.5002 g, 2 mmol) 0.1 M methanol solution of NaOH was added dropwise till pH of 8 was reached (10 mL, 1

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mmol). To this solution 0.7 mmol of CuCl2, dissolved in 7 mL methanol, were added while stirring. Light purple colored precipitate is formed and isolated by filtration and washed with methanol. The yield was 0.332 g (71.4 %). Anal. calcd for C30H28CuN4O9 [Cu(L1-)2.5H2O]: C: 55.29; H: 4.33; N: 8.60 %. Found: C: 54.89; H: 3.94; N: 8.44 %.

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Synthesis of Cu(II)-L2: To a solution of L2 (0.5327 g, 2 mmol) in 10 mL of methanol 20 mL of 0.1 M methanol solution of NaOH (2 mmol) was added dropwise (pH 9). To this solution 11 mL of 0.1 M methanol solution of CuCl2, (1.1 mol) were added and stirred until

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green precipitate was formed. The solid was filtered off, repeatedly washed with methanol and dried over P4O10 for two weeks. The yield was 0.295 g (40.3 %). Anal. calcd for

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C30H26CuN4O6S2 [Cu(L2-)2.4H2O]: C: 54.13; H: 3.94; N: 8.42; S: 9.61 %. Found: C: 53.72; H: 3.65; N: 8.31; S: 10.01 %.

The solids isolated from the reacting mixtures of the Cu(II) salts (CuCl2 and

Cu(CH3COO)2.H2O) with the ligands L1 and L2 without adding strong base, were proved to be the non-reacted free ligands.

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ACCEPTED MANUSCRIPT 2.3. Theoretical calculations

Quantum chemical calculations were performed using Gaussian 09 suite of programs [41]. Geometries of the studied compounds were optimized using the DFT method with the

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hybrid B3LYP functional [42, 43] and the 6-31G(d,p) basis set. The fluorene- and cyclopentane-substituted hydantoins and their thio-analogues (depicted in Fig. 1) were further optimized in their neutral form as well as in the form of monoanions, formed after

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deprotonation of either N3-H or N1-H groups, using the Dunning’s correlation consistent basis sets cc-pVTZ [44]. In all cases the vibrational frequencies and intensities were

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computed at the same level of theory and confirmed the attainment of local minimum. The calculated vibrational frequencies were scaled with factor of 0.9806 and compared with the experimental data. Unrestricted DFT (B3LYP/6-31G(d,p) was used for the geometry optimizations of the Cu(II) complexes. Calculations of the EPR parameters (the g-factor and

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A-tensor) were performed on the optimized structures using the ADF.2008.01 program [45]. For this we used the GGA functional, BLYP [46, 47] or the dispersion corrected functional BP86-D [48], and the TZ2P basis sets, as implemented in the ADF package. The relativistic

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effects were taken into account by employing the ZORA and the Scalar Pauli relativistic approximations. For these calculations all-electron or frozen medium-core were considered.

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The obtained values for the principal axis g- and A- tensors were compared with the experimental data without any scaling.

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ACCEPTED MANUSCRIPT 3. Results and Discussion

3.1. Synthetic procedures

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The studied fluorene-spiro-5-hydantoins were obtained according to a literature procedure [35] and their molecular formulas are presented in Fig. 1. Based on the available knowledge about the complexation abilities of 2,4-dithiohydantoins, herein we explored the

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influence of the reaction conditions on the formation of Cu(II) complexes of L1 and L2. Reactions with different metal salts in alcohol medium in presence or absence of a strong

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base, NaOH, were performed. The complex formation was checked by IR spectroscopy and elemental analyses. Our results showed that L1 and L2 form Cu(II) complexes only when CuCl2 and NaOH are used, which is similar to the complexation behavior of cycloalkane-2,4dithiohydantoins [33] but is in contrast to the fluorene-bearing dithiohydantoin L3 [34] (vide

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supra). The reaction products were isolated as amorphous precipitates in the form of noncharged complexes. The elemental analyses and the IR data indicated that the reaction of L1 and L2 with Cu(II) acetate in non-alkaline medium do not lead to complex formation, and the

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unreacted ligand was isolated. Only the products obtained in presence of NaOH confirmed the formation of Cu(II) complexes of L1 and L2. These were subjected to further spectroscopic

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and theoretical analyses in order to elucidate their geometry because good quality single crystals could not be obtained. The elemental analyses data indicate a M:L ratio of 1:2 with additional coordination of water molecules. The registered EPR spectra at room temperature prove that the formed complexes are in oxidation state +2 of the copper ion.

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ACCEPTED MANUSCRIPT 3.2. Spectroscopic characterizations

The complexes were experimentally characterized by IR and EPR spectroscopy. The elemental analyses suggest the coordination of two ligands to each metal centre with

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additional coordination of two water molecules. The EPR spectroscopy unequivocally shows that the complexes are paramagnetic with a d9 electronic structure of the central Cu(II) ion. The experimental IR spectra of the ligands L1 and L2 and the corresponding Cu(II)

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complexes are compared in Fig. 2. Selected vibrational frequencies from the experimental IR spectra and the DFT calculations of the complexes and the free ligands are listed in Table 1.

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In the IR spectrum of the Cu(II) complex of L1 a significant red shift of the carbonyl groups vibrations is seen (from 1776, 1733, 1716 cm–1 in the free ligand to 1717, 1645 cm–1 in the complex). This observation may suggest coordination of a carbonyl group. It should be noted also that the experimental IR spectrum of the free ligand shows a clear splitting of the

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lower-frequency carbonyl vibration that could be related to solid state effects, such as hydrogen bonds that are present in the crystal structure of L1 [36]. Other strong changes that appear in the spectrum of Cu(II)-L1 concern the amide vibrations, involving the free ligand

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bands at 1236 and 1398 cm–1 which shift to 1268 and 1380 cm–1 in the complex and become much broader and intense (Fig. 2). Similar trends for the amide stretching vibrations exist in

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the spectrum of the Cu(II)-L2 complex, accompanied with broadening of the carbonyl groups vibrations (Fig. 2). For both complexes the deformational vibrations of the amide groups at ca. 1100 - 1200 cm-1 shift to higher frequencies, split into several components and broaden. The stretching vibrations of the N-H groups are clearly seen in the spectra of the free ligands, but not in the spectra of the Cu(II)-L1 and Cu(II)-L2 complexes due to the broad bands present at ca. 3410 and 3380 cm–1, respectively. These bands correspond to the vibrations of coordinated water molecules, as was also suggested from the elemental analyses.

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Absorbance

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L1

0,7

Cu(II)-L1 0,6

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0,5 0,4 0,3

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0,2

0,0

1000

1500

0,8

2000

-1

ν [cm ]

2500

0,7

0,6

3500

Cu(II)-L2

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0,5

3000

L2

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Absorbance

500

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0,1

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0,4

0,3

0,2

0,1

500

1000

1500

2000

2500

3000

3500

-1

ν [cm ]

Figure 2. Comparison of the IR spectra (KBr) of the free ligands L1 and L2 (grey lines) and the corresponding Cu(II) complexes (bold lines).

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ACCEPTED MANUSCRIPT Due to the strong coupling between the carbonyl and the N-H groups in the hydantoin ring, isolated vibrations for these functionalities could not be detected. This fact hampers the straightforward determination of the coordination modes of hydantoins basing solely on IR spectroscopy, since both carbonyl and amide vibrations change upon coordination. Based on

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our previous studies on dithiohydantoins, we suppose that the described changes are caused by coordination of the N-atoms from the hydantoin ring but not the carbonyl or thio-carbonyl groups. This is supported by the recorded EPR spectra that are very informative for the

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coordination environment of the Cu(II) centres. As was already mentioned, the observation of EPR spectra at 293 and 77 K confirms the stabilization of the paramagnetic Cu2+ (d9) state of

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the metal centres. The EPR spectrum of the Cu(II)-L1 complex shows composite structure with well-defined anisotropy of the g-factor and presence of hyperfine (hf) and superhyperfine (shf) structure (Fig. 3). Thus, the spectrum provides valuable information for the coordination geometry of the Cu(II) centre, indicating the direct coordination of N-atoms.

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The experimental spectra were computer simulated for a system with S=1/2 and accounting for the hyperfine coupling with

63,65

Cu nuclei (I=3/2) and the superhyperfine coupling with

the 14N nuclei (I=1). The best-fit results from the computer simulated spectra are shown in Fig.

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3. The estimated g–values are as follows: gx = 2.032, gy = 2.058 gz = 2.212 at room temperature. Superhyperfine structure due to interaction with

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N nuclei (I=1) is observed at

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the high-field end of the spectrum. The estimated coupling constant Ashf is 14 G (13.4×10-4 cm-1) with relative intensity of the superhyperfine lines 1:2:1, which is typical for the nuclei. In the studied spectra, well-defined hyperfine structure due to

14

N

63,65

Cu nuclei is seen in

parallel direction with a hyperfine coupling constant, Ahf, of 157 G (162.1×10-4 cm-1) as estimated from the best-fit computer simulation. The EPR spectrum of the Cu(II)-L2 complex, however, is rather broad in the perpendicular direction, and the superhyperfine coupling with the

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N nuclei could not be resolved even at lower temperatures. The EPR

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ACCEPTED MANUSCRIPT parameters, gx = gy = 2.080 gz = 2.230 and A‫=׀׀‬180 G (187.4×10-4 cm-1), are listed in Table 1, too.

Cu(II)-L2

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Cu(II)-L1

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Figure 3. Experimental (solid line) and computer simulated (dashed line) EPR spectra of the Cu(II) complexes of L1 (left) and L2 (right).

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ACCEPTED MANUSCRIPT Table 1. Comparison between experimental and calculated IR and/or EPR data for the free ligands L1 and L2 (B3LYP/cc-pVTZ), and their metal complexes, Cu(II)-L1 and Cu(II)-L2 as obtained for two UB3LYP/6-31G(d,p) optimized model structures for the complexes (model 1 and model 2 with compositions CuL-2.2H2O and CuL2Cl2). Calculated vibrational frequencies (υ, cm-1) are calibrated with factor 0.9806. The EPR parameters; g-factors and the hyperfine coupling constants A (in 10-4 cm-1) are obtained from BP-86-D/TZP(2P) relativistic (Scalar Pauli) and the BLYP/TZP(2P) relativistic (Scalar ZORA) calculations, respectively.

557.3

Cu-L1 Cu-L1 model 1 model 2 722.0 743.4

experimental IR L2 Cu(II) -L2 734 s 734 vs

737 s

737 s

742.4

738.7

756 m

990 w

779 w

965.6

1150 m

1015 m 1086 w

1085.8

1167 s

L1

766 s

L2

Cu-L2 Cu-L2 model 1 model 2 740.9 737.4 738.1

996.0

891.9

792.3

1148.8

1173.0

1177.1

1203 vs 1181.8 1226 vs

1211.5

1212.9

1191 s

1262.4

1199.1

1264.4

1380 s 1321.8 1450 m 1450 m 1348.2

1367.3

1349.8

1266 vs 1335.9 1374 m 1393 s 1349.1

1382.6

1432.4

1384.8

1447.3

1505 s

1716 vs 1645 vs

1594.4

1733 vs 1717 m

1715.0

1776 vs

1786.4 1819.2

1711.8

1450 vs 1495.0 1476 vs

1455.6

1516.5

1469.7

1528.2

1627 w

1598.0

1729 s

1731.2

1746.6

1730 vs

1763.3

1845.8

1752 s

1799.4

1776.9

1839.4

3138.4

3267.4

3296.8

3194.9

3198.0

3603.4

3090 br 3059 br 3132.8 3158 br 3375 br 3564.1

3595.6

3592.8

gx = 2.032,

calculated EPR Cu-L1 Cu-L1 model1 model2 g1 = 2.033, g1 = 2.042,

gy = 2.058,

g2 = 2.049,

g2 = 2.047,

gz = 2.212,

g3 = 2.134,

g3 = 2.142,

A‫ = ׀׀‬162.1

A max= 269.9 A iso = 167.5

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experimental EPR

1237.2

1746.0

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3193 s 3046 br 3567.4 3362 s 3411 br 3587.4

1530 s

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1398 s

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1176.5

1236 m

1210 w 1178.5 1268 m 1200.0

751.0

calculated IR

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calculated IR

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experimental IR L1 Cu(II)L1 683 m 686 w

A max= 5.9 A iso = 5.5

experimental EPR gx = gy = 2.080, gz = 2.230, A‫ =׀׀‬187.4

calculated EPR Cu-L2 Cu-L2 model1 model2 g1 = 2.037, g1 = 2.020, g2 = 2.042,

g2 = 2.,045

g3 = 2.144,

g3 = 2.099,

A max= 273.6 A iso = 176.2

A max= 22.5 A iso = 22.7

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ACCEPTED MANUSCRIPT 3.3. Theoretical modelling for geometry determination of the complexes

Although monodentate coordination through deprotonated NH groups of L1 and L2 monoanions was experimentally suggested, the possible coordination of the carbonyl groups

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remained under question due to the observed red shifts of their stretching vibrations. Therefore, we undertook quantum chemical calculations of various model structures of the complexes, including the less probable ones, in order to more convincingly verify the

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structure suggested by the experiments and rule out the coordination of carbonyl groups. This has been achieved by calculations of the spectral properties for the different model structures

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of the complexes and direct comparison with the available experimental data as a final verification step. Herein we present only two of the possible models of non-charged tetrahedral Cu(II) complexes that have been considered for Cu(II)-L1 and Cu(II)-L2; model 1 with monodentate coordination of two monoanionic ligands by their deprotonated N-atom

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and two water molecules; and model 2 where two ligand molecules coordinate by their carbonyl/thio-carbonyl O(S)-atom and two chloride ions are coordinated to neutralize the charge of the Cu(II) centre. The optimized structures for model 1 and model 2 of the

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complexes are given in Fig. 4 and Fig. 5, respectively. In all structures the fluorene ring remains perfectly perpendicular to the hydantoin fragment.

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Some of the calculated structural parameters for the optimized free ligands and their

vibrational frequencies are compared with those of the model structures of the complexes in Table 2. The calculated bond lengths from the hydantoin ring are compared with the available X-ray data for L1 [36]. As could be expected, the major differences between the gas-phase optimized structure of L1 and the crystallographic data appear for the groups that are involved in intermolecular hydrogen bonds that form infinite network in the crystal packing, namely C2-O2, N1-C2 and N3-C2. The changes in the bond lengths in the hydantoin ring that result from the different types of coordination (that is by N3-atom in model 1 or by C2-O2/C2-S2 15

ACCEPTED MANUSCRIPT group in model 2) reach ca. 0.025 Å for the groups directly involved in the coordination. Interestingly, the C4-O4 bonds in model 1 structures for Cu(II)-L1 and Cu(II)-L2 also elongate (by 0.030 and 0.025 Å, respectively) although they are not directly involved in coordination. The explanation is that C4-O4 participates in strong hydrogen bonds with the

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coordinated water molecules as is seen in the optimized structures of models 1 of the complexes, depicted in Fig. 4. These structural features directly reflect the calculated vibrational frequencies for the optimized model 1 structures of the complexes (see Table 1)

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and describe correctly the experimentally observed red shift of the carbonyl vibrations (at 1776 and 1752 cm-1 for L1 and L2, respectively) for both complexes, Cu(II)-L1 and Cu(II)-

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L2 (Fig. 2). Further support for model 1 structure of the complexes, with coordinated monoanionic form of the ligands, is obtained by the strong changes in the amido groups vibrations that are seen both in the experimental and in the calculated frequencies. For example, experimental and calculated spectra of Cu(II)-L2 show analogous shift and splitting

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of the free ligand vibrations from 1167 and 1191 cm-1 to 1203, 1226 and 1266 cm-1, according to the experiment, and from 1148.8 and 1181.8 cm-1 to 1211.5, 1237.2 and 1264.4 cm-1, according to model 1 of Cu(II)-L2. Such trends for model 2 are not seen. These analyses

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supports the suggested model 1 of the complexes with distorted tetrahedral structure and two water molecules coordinated to the metal ion. Throughout the described theoretical analyses

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we use model 2 to demonstrate that coordination by O2/S2 atoms in the studied complexes does not take place. We also checked theoretically the possible coordination by O4 donor atoms, as isomeric forms of models 2, and the results from the frequency calculations firmly rule out this possibility, too (see Supplementary material.)

16

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ACCEPTED MANUSCRIPT

Figure 4. Optimized structures (UB3LYP/6-31G**) of the Cu(II)-L1 and Cu(II)-L2 complexes with composition CuL-2.2H2O (model 1).

17

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ACCEPTED MANUSCRIPT

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Figure 5. Optimized structures (UB3LYP/6-31G**) of the Cu(II)-L1 and Cu(II)-L2 complexes with composition CuL2Cl2 (model 2).

18

ACCEPTED MANUSCRIPT Table 2. Calculated structural parameters for the free ligands L1 and L2 (B3LYP/cc-pVTZ), and their metal complexes, Cu(II)-L1 and Cu(II)-L2 (UB3LYP/6-31G(d,p) as obtained for two model structures for the complexes (model 1 and model 2 with compositions CuL. 2 2H2O and CuL2Cl2, respectively).

L1

C2-O(S)2

1.236(3)

1.206

C4-O4

1.202(3)

1.201

N1-C2

1.336(3)

1.365

N1-C5

1.455(4)

1.453

N3-C2

1.387(3)

1.407

N3-C4

1.369(3)

1.374

C4-C5

1.455(4)

1.453

Cu-N3(O/S2)’ Cu-N3(O/S2)’’

Cu-Ow(Cl)’’ angles

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Ow-Cu-Ow /

O’-Cu-O’’ /

1.974

N(S)’-Cu-N(S)’’

L2

Cu-L2 Cu-L2 model 1 model 2 1.687/ 1.693/ 1.693 1.693 1.228/ 1.203/ 1.215 1.203 1.351/ 1.344/ 1.355 1.344 1.451/ 1.462/ 1.456 1.462 1.385/ 1.365/ 1.365 1.344 1.375/ 1.396/ 1.379 1.396 1.552/ 1.559/ 1.564 1.559 1.978 2.410

1.651 1.200 1.350 1.456 1.387 1.380 1.456

1.980

1.924

2.410

1.932

2.230

2.018

2.235

1.935

2.230

1.952

2.235

150.8

104.8

155.2

145.9

148.8

86.5

166.3

133.5

94.1

100.1

92.8

90.6

94.1

134.6

90.3

102.8

93.7

100.1

90.4

90.6

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Cu-Ow(Cl)’

Cl-Cu-Cl

Cu-L1 Cu-L1 model 1 model 2 1.245/ 1.236 1.245 1.203/ 1.232 1.203 1.350/ 1.365 1.350 1.461/ 1.449 1.461 1.376/ 1.397 1.376 1.391/ 1.362 1.391 1.564/ 1.559 1.564 1.974 1.980

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L1

calculated

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Str. parameter

calculated

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experimental *

Ow’-Cu-N’ / Cl’Cu-O(S)’

Ow’-Cu-N’’ / Cl’Cu-O(S)’’ Ow’’-Cu-N’’ / Cl’’-Cu-O(S)’’ *

data taken from [36]

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ACCEPTED MANUSCRIPT Besides the calculated IR frequencies of the optimized model structures of the complexes, further evidences in favour of model 1 were obtained from the calculated EPR parameters. The calculated g-factors and A-tensors for both model structures of Cu(II)-L1 and Cu(II)-L2 are compared with the experimental data in Table 1. While the calculated

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values for the g-factors for both models are rather similar, the calculated A-tensors show stark distinction. After comparison with the experimental data a clear preference to model 1 can be suggested. Thus, although at a qualitative level, the calculations of the EPR parameters could

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provide additional strong evidence in support of the coordination of the fluorene-hydantoin ligands by their deprotonated N3-atom and formation of strongly flattened tetrahedral

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complexes. The strong flattening of the tetrahedral geometry is seen from the bond angles involving the metal centre, which show large deviation from 109 0 (see model 1 in Table 2).

3.4. Elucidation of the structural and electronic effects on the spiro-hydantoins’ complexation

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properties

Additional aim of the presented work is to elucidate the reasons for the previously

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reported distinct reactivity of dithio-analogues of spiro-5-hydantoins that depends on the substituents at the spiro-5-atom [33, 34]. Basically this concerns the deprotonation ability of

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the N3-H group, which usually participates in coordination with Cu(II) and is related to the stabilization of the +2 oxidation state of copper. Alternatively, if S-atom from the thione groups is coordinated, the Cu(I) will be stabilized. Therefore, in order to obtain stable Cu(II) complexes a strong base must be used to deprotonate the hydantoins N3-H group, as was presently seen for L1 and L2, and previously reported for the cycloalkane-spiro-5dithiohydantoins [33]. The only exception is the fluorene-spiro-5-dithiohydantoin (L3 in Fig. 1) that has been reported to form stable Cu(II) complexes in absence of strong base [34], which is in contrast to the complexation properties of L1, L2 and the cycloalkane-spiro-5-

20

ACCEPTED MANUSCRIPT dithiohydantoins. Such unexpected coordination properties of the studied series of spiro-5dithiohydantoins prompted our theoretical investigation on the deprotonation enthalpies of the fluorene-substituted and cyclopentane-substituted spiro-5-hydantoins and their mono- and dithio- analogues, all shown in Fig. 1. Thereby, optimizations and Hessian diagonalization

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have been performed of all six structures in their neutral and monoanionic forms with deprotonated N3-H or N1-H groups. The total energies and zero-point vibrational energies (ZPVE) were calculated. Enthalpies were evaluated by considering the thermal corrections at

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298.15 K. The gas-phase acidities were calculated as deprotonation enthalpies, ∆H298, for the

LH (g) → L- (g) + H+ (g)

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reaction

The equation used for calculation of enthalpy of deprotonation, ∆H298, takes the form ∆H298= ∆Etot + ∆ZPVE + ∆(H298 – H0) + 1.48 kcal/mol and was derived from the following expressions [49, 50]

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∆H298 = ∆E298 + ∆(pV)

∆E298 = [E298(L-)+3/2RT] – E298(LH), where E298 stands for the total energy of the compounds in their neutral or monoanionic forms. The thermal energy correction at T =

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298.15 K was included and the ∆(pV) was substituted with RT, for one mole of gas obtained in the deprotonation reaction. The data are listed in Table 3 along with the Mulliken charges

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on the heteroatoms from the hydantoin ring in the studied compounds. Analyses of the obtained theoretical data outline the following trends: i) the enthalpy

of deprotonation is always smaller for the N3-H group of the fluorene-substituted compounds, suggesting its more acidic character, whereas for the cyclopentane-substituted hydantoins this is true only for the dioxo-analogue; ii) replacing the O-atoms with sulfur leads to decrease in the deprotonation enthalpies of both types of hydantoins, which results in increased acidity of the thio-analogues; iii) replacing the cyclopentane substituent with a fluorene ring leads to

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ACCEPTED MANUSCRIPT decrease in the deprotonation enthalpies, which is always more pronounced for the N3-H group (up to 7-8 kcal/mol for L2 and L1), i.e. suggests increased acidity of the fluorenehydantoin; iv) the most acidic of all calculated hydantoins is the fluorene-spiro-5dithiohydantoin L3, especially the N3-H group. These data could be related to the

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experimentally observed complexation properties of the discussed hydantoin ligands, namely with the fact that L3 forms Cu(II) complexes from Cu-acetate without the need for initial deprotonation with a strong base, whereas for all other hydantoins such deprotonation is

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required for complex formation. The calculated Mulliken charges are in accordance with the observed trends in the deprotonation energies and also with the complexation properties of the

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compounds. The highest electron density is localized on the S2/O2 atoms, which is related to their better donor ability in coordination with the metal ion, and also the lowest density is always on N3 atom suggesting the ease of the deprotonation of the corresponding N-H group. Whereas all calculated charges for the listed heteroatoms are negative, the N3 atom of L3 is

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the only exception having small but positive charge.

With the presented results we have succeeded to describe the general relations between the structural modifications and the complexation properties of the studied series of

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hydantoin derivatives using theoretical and experimental methods. Although qualitative agreement was achieved, a more thorough theoretical investigation of the eventual forces for

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through-bond electron-density distribution in such non-conjugated systems can be of future fundamental interest.

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ACCEPTED MANUSCRIPT Table 3. Calculated (B3LYP/cc-pVTZ) total energies, deprotonation enthalpies and Mulliken charges of selected atoms of the studied hydantoins in their neutral and/or monoanionic forms. For structures and atom numbering see Fig. 1. N1- and N3- designate the monoanions formed by deprotonation of the corresponding amido-nitrogens.

-

L2-N1 L2-N3L3 L3-N1 L3-N3

cy5-dioxo cy5-dioxo-N1 cy5-dioxo-N3 cy5-2-thio

-

cy5-2-thio-N1 cy5-2-thio-N3cy5-dithio cy5-dithio-N1 cy5-dithio-N3

137.842 128.900

-525652.117 -525307.179

-837.361653 -1160.871797 -1160.321534 -1160.326695 -1483.828174 -1483.285263

129.125 136.572 127.866 127.763 135.111 126.573

-525314.162 -728311.968 -727975.527 -727978.869 -930971.386 -930639.410

126.331 -108.318 99.707

-930641.588 --334323.326 -333973.344

331.28

99.941 107.076 98.626 98.532 105.691 97.350

-333977.614 -536983.456 -536643.520 -536643.635 -739643.565 -739309.816

347.19

335.23

97.040

-739309.904

335.14

-1483.288463 --532.961404 -532.389526 -532.396557 -855.919038 -855.363696 -855.363676 -1178.876729 -1178.331288 -1178.330918

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L1-N3 L2

-837.914569 -837.350269

346.42 339.43

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L1-N1

-

ZPVE [kcal/mol]

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L1

Total energy [a.u.]

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Geometry

ZPVE and Therm. Deprotonation Corrected Total enthalpy Energy [kcal/mol] [kcal/mol]

337.92 334.58 333.46

351.46

341.42 341.30

S4/O4 -0.273 -0.265 -0.212

N3 -0.092 -0.052 0.007

S2/O2 -0.312 -0.310 -0.299

N1 -0.155 -0.110 -0.103

cy5-dioxo cy5-2-thio cy5-dithio

-0.304 -0.295 -0.238

-0.099 -0.064 -0.013

-0.317 -0.324 -0.311

-0.173 -0.132 -0.122

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geometry L1 (dioxo) L2 (2-thio) L3 (dithio)

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Mulliken charges (at atoms)

Acknowledgements. Financial support by the National Science Fund of Bulgaria (Contracts DFNI BO1/0014 and DMU-02/11) is gratefully acknowledged.

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ACCEPTED MANUSCRIPT References:

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ACCEPTED MANUSCRIPT Highlights to manuscript: An integrated experimental and quantum chemical study on the complexation properties of (9’-fluorene)-spiro-5-hydantoin and its thioanalogue


fluorene-spiro-5-hydantoins form Cu(II) complexes only in presence of a strong base

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experimental and DFT-calculated EPR parameters allowed for geometry verification

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Electronic and structural effects on the complexation abilities of spiro-hydantoins

1