Synthesis, spectra, crystal structure, Hirshfeld surface analysis, DFT calculations and molecular docking evaluation on novel mononuclearZn(II), Mn(III) and Co(III) Schiff base complexes derived from 2- hydroxy-1-naphthaldehyde

doi:10.21203/rs.3.rs-2865691/v1

four novel complexes of bidentate Schiff base ligand derived from 2-hydroxy-1-(2-methoxyethylimino)-naphthalen (HL) were synthesized and characterized using elemental analysis, FTIR, and UV–Vis spectroscopies. X-ray single crystal structures of Zn(II), Mn(III) and Co(III) complexes (1–4) have also been determined, and it was indicated that these Zn(II) and Co(III) complexes (1, 4) are in an octahedral geometry. Whereas, it was found that the Zn complex (2) in quite a regular tetrahedral environment. Also, Mn center in complex (3), is ligated by two azomethine nitrogen atom, two ligand oxygen atoms and one Cl atom of metal salt forming five coordinated tetragonal pyramid geometry around of the Mn atoms. The cyclic voltammetry (CV) of the complexes specifies an irreversible redox behavior for all complexes (1–4). Next, the molecular electrostatic potential (MEP) was studied for all complexes to better understand and predict the reaction sites of electrophilic and nucleophilic attacks. Also, density functional theory (DFT) calculations were performed to determine the optimal geometrical configurations, and comparison between experimental and theoretical data, and non-covalent interactions were determined by Hirshfeld surface analysis (HSA) using CrystalExplorer program. Also, finding binding affinity of complexes with protein (PDB ID: 4LXD) was also done using molecular docking.

Complex

2-hydroxy 1-naphthaldehyde

Crystal structure

electrochemical properties

DFT study

Hirshfeld surface analysis

Molecular docking studies

Schiff base is a type of organic chemical that has wide applications. Carbonyl molecule is used to produce compounds with azomethine group (-CH = N-), Schiff bases [1–2]. For the last several decades, chemists have been interested in the coordination chemistry synthesis of Schiff base ligands. Because these compounds are of particular importance for the synthesis of metal complexes due to their ability to create coordination bonds with a wide range of metal ions, as well as Schiff bases due to the ease of production and high metal binding ability [1–3]. Metal complexes of Schiff bases have gained a lot of attention in recent years due to their exceptional antifungal, antibacterial, antitumor, and anticancer properties [4]. Other biological activities of Schiff's base include anti-inflammatory, analgesic, anti-allergic, antioxidant, reduction of free radical activity and insecticidal properties of these compounds [5]. Some Schiff base complexes have the property of very fast dyeing of food, wool and skin [6]. Structural changes, such as changing the type of central metal, replacing a different ligand, have been used in a variety of ways and have attracted a lot of attention [7–9]. A large amount of Schiff base complexes by means of 2-hydroxy 1-naphthaldehyde derivatives have been reported [10–13]. Abbasi et al. synthesized Ni(II), Cu(II) and V(IV) complexes by 2-hydroxy 1-naphthaldehyde and 2-methoxyethylamine derivatives and studied the anticancer activity of these compounds against gastric cancer [14]. Docking studies on Schiff base complexes obtained from 2-hydroxy 1-naphthaldehyde and allylamine were performed in 2016 and 2022, the results obtained from molecular docking showed that the presence of metal in the compounds causes that compounds are attached to the amino acid in a suitable orientation and binding [13, 15]. Didarul A. Chowdhury and co-workers synthesized dioxouronium(VI) complexes of derivatives, 2-hydroxy-1-naphthaldehyde, each of which Schiff base complexes are bivalent anions with tridentate ONS donors [16]. In accordance with these facts shown, the importance and significant applications of the Schiff compounds, the authors became interested in preparing Schiff base ligands (HL) by condensation 2-hydroxy-1-naphthaldehyde with 2-methoxyethylamine and then new series of four novels Zn(II), Mn(III), and Co(III) complexes (Scheme 1). All synthesized compounds were characterized using several spectroscopic tools. The crystal structures of the complexes were determined by the single-crystal X-ray diffraction. DFT theoretical calculations were compared with experimental data UV-Vis spectra. To predict the possible binding modes between the tested compounds and the active sites of the receptors, molecular binding studies were performed. Furthermore, electrochemical properties of complexes were determined by cyclic voltammetry. Hirshfeld surface analysis (HSA) and molecular electrostatic potential (MEP) were performed to explain extra interesting structural features of complexes.

2.1. Materials and methods

All the chemicals were of reagent grade and were purchased from Merck and Sigma-Aldrich companies and utilized without further purification. A SHIMADZU FT-IR spectrophotometer was applied to record Infrared (IR) spectra, where the samples were prepared into KBr (400–4000 cm^− 1) pellets. UV–Vis absorption spectra were determined on a UV-1650 PC SHIMADZU spectrophotometer in acetonitrile solution. Electrochemical experiments were recorded on a Metrohm 757 VA Computrace instrument at room temperature in a DMSO solution. Elemental analysis was prepared by a Perkin-Elmer 2400II CHNS-O elemental analyzer. Schiff base ligand of the reaction via 2-hydroxy 1-naphtaldehyde and 2-methoxyethylamine was prepared affording to the method reported in ref. [14].

2.2. Synthesis of [Zn^II(HL)₂ CH₃OH] (1), [Zn^II(HL)₂] (2)

complex was synthesized by the template method. 1 mmol (0.0172 g) of 2-hydroxy 1-naphthaldehyde was dissolved in 10 mL of methanol, then 1 mmol (0.075 g) of 2-methoxyethylamine was dissolved in 5 mL methanol was dissolved and added to it and refluxed with a magnetic stirrer on a heater at a temperature of 50°C for two hours. Then 0.5 mmol (0.112 g) of zinc bromide (ZnBr₂.2H₂O) was dissolved in 10 mL of methanol, it was slowly added to the solution. The color of the solution did not change after adding the metal, two drops of TEA were added to it after half an hour. The color of the solution changed from yellow to red, and the solution was refluxed for 8 hours. The solution was filtered and placed at room temperature, and after 5 days, brown crystals formed in the solution, and the crystals were filtered using a vacuum pump. This compound was subjected to X-ray analysis and the phenomenon of morphism was observed in it.

Yield: 60%. Mol. Wt: 553.93, 521.89 g/Mol. Anal. Calc. For C₂₉H₃₂N₂O₄Zn, C₂₈H₂₈N₂O₄Zn, C, 70.43; H, 5.83; N, 5.21. Found: C, 70.61; H, 5.48; N, 5.43. FT-IR: v_max cm^− 1 (KBr): 580, 1355, 1461, 1618, 3421. λ_max (nm)(ε, M^− 1cm^− 1)(CH₃CN): 234(68000), 250.5(39000), 311(19000),403.5(21000), 418.5(20000).

2.3. Synthesis of [Mn^III(HL)₂ Cl] (3)

[Mn^III(HL)₂ Cl] Complex (3) was synthesized similarly the complex (1) procedure, excepting that MnCl₂.2H₂O was used instead of ZnBr₂.2H₂O. In this solution, a black precipitate was observed after a few days. The precipitate was recrystallized in 3 and 7 mL of dimethyl sulfoxide and methanol, respectively. After 7 days, very shiny triangular crystals were formed in the solution and separated from the solution by a vacuum pump.

Yield: 78%. Mol. Wt: 546.91 g/Mol. Anal. Calc. For C28H28ClMnN2O4, C, 51.31; H, 5.53; N, 4.98. Found: C, 51.35; H, 5.68; N, 5.05. FT-IR: v_max cm^− 1 (KBr): 572, 1361, 1454, 1616, 3421, λmax (nm)(ε, M^− 1cm^− 1)(CH₃CN): 230.5(58000), 249(23000), 306(17000), 330(14000), 396(15000), 429(16000), 484(600).

2.4. Synthesis of [Co^III(HL)₃] (4)

The ligand yellow solution which was synthesized the same method as complex (1), replacing Co(OAc)₂.4H₂O as the salt, was refluxed for 24 h. After this period, a thick green precipitate was formed in the solution, which was separated by filter paper and recrystallization was performed in DMSO and acetonitrile (3 and 5 ml, respectively). After 13 days, a very shiny and green crystal in this The solution was filtered and separated by a vacuum pump.

Yield: 84%. Mol. Wt: 743.71 g/Mol. Anal. Calc. For C₄₂H₄₂CoN₃O₆, C, 70.21; H, 6.26; N, 5.40. Found: C, 70.34; H, 6.19; N, 5.56. FT-IR: v_max cm^− 1 (KBr):524, 1361, 1436, 1606, 3425. λ_max (nm)(ε, M^− 1cm^− 1)(CH₃CN): 208(100000), 231(68000), 275(90000), 322(40000), 438(18000), 675(398).

2.5. X-ray single crystal data collection and refinement

X-ray diffraction data were collected at room temperature (1, 3) and at 100(1) K (2, 4) by the ω-scan technique on an XCalibur four-circle diffractometer (Eos CCD detector with a graphite-monochromatized MoKα radiation source, λ = 0.71073 Å). The data were corrected for Lorentz-polarization and absorption (multiscan method) effects. The structures were solved with SHELXT and refined using the full-matrix least squares procedure on F² by using SHELXL [17–19]. Hydrogen atoms were placed at the calculated positions, and refined as a ‘riding model’ with the isotropic displacement parameters set at 1.2 (1.5 for methyl groups) times the U_eq value for appropriate non-hydrogen atoms. The structure 1 turned out to be twinned, which was considered in both data collection and refinement procedures. The TWIN parameter (SHELXL), which shows the relative contents of two components, refined at 0.665(7)/0.335(7). The structure of 1 contains additional solvent – methanol molecule. Table 1 lists the relevant information about crystal structure, data collection and refinement results.

Table 1

Crystal data, data collection and structure refinement
Compound		1	2	3	4
Formula	C₂₈H₂₈N₂O₄Zn · CH₃OH		C₂₈H₂₈N₂O₄Zn	C₂₈H₂₈ClMnN₂O₄	C₄₂H₄₂CoN₃O₆
Formula weight		553.93	521.89 /c	546.91	743.71
Crystal system		monoclinic	monoclinic	tetragonal	monoclinic
Space group		P2₁/n	C2	P4₁2₁2	P2₁/c
a(Å)		10.0900(8)	25.219(3)	8.1438(2)	13.5687(5)
b(Å)		12.5529(9)	5.2463(11)	8.1438(2)	11.1821(3)
c(Å)		20.6545(12)	9.3784(11)	37.8856(14)	23.5870(6)
α(º)		90	90	90	90
β(º)		91.171(7)	94.508(12)	90	95.480(3)
γ(º)		90	90	90	90
V(Å³)		2615.5(3)	1237.0(3)	2512.63(15)	3562.42(19)
Z		4	2	4	4
D_x(g cm^− 3)		1.407	1.401	1.446	1.387
F(000)		1160	544	1136	1560
µ(mm^− 1)		0.981	1.030	0.670	0.536
Reflections:
collected		10244	6392	6017	14471
unique (R_int)		4586 (0.033)	3213 (0.084)	2724 (0.023)	7684 (0.018)
with I > 2σ(I)		3866	2525	2277	6468
R(F) [I > 2σ(I)]		0.0709	0.0614	0.0415	0.0420
wR(F²) [I > 2σ(I)]		0.1888	0.1509	0.0982	0.1053
R(F) [all data]		0.0843	0.0780	0.0537	0.0532
wR(F²) [all data]		0.1948	0.1728	0.1054	0.1126
Goodness of fit		1.066	1.083	1.071	1.032
max/min Δρ (e·Å⁻³)		0.89/-0.78	0.74/-0.76	0.21/-0.34	1.17/-0.49
CCDC number		2239745	2239744	2239746	2239747

Table 1

2. 6. Cyclic voltammetry

To study the cyclic voltammetry of the complexes, a three-electrode system including silver electrode as reference electrode, platinum electrode as auxiliary electrode and glass electrode as working electrode was used at ambient temperature and nitrogen gas atmosphere. To record the cyclic voltammograms related to the complexes in each case, a solution with a concentration of 10^− 3 M in DMSO solvent was prepared in the presence of an electrolyte agent carrying 0.1 M of tetrabutylammonium hexafluorophosphate (TBAH). The anodic and cathodic potentials for the complexes are reported relative to the Ferrocene potential (the electrochemical potentials were calibrated versus internal Fc^+/o (E⁰ = 0.45 V)).

2. 7. Hirshfeld surface analysis

Hirshfeld surface analysis (HSA) [20–23] is a useful tool to gain quantitative descriptions of the intermolecular interactions in molecules. Crystal Explorer 17 software [24] was used to reveal the non-covalent interactions in the studied complexes. The Hirshfeld surface analysis and two-dimensional fingerprint plots were used to discover the significant non-covalent interactions [25]. As well as, we mapped d_norm surface with a range of -0.106 to 8.383 Å. The shapes index ranges − 1.000 to 1.000 Å were calculated. In three-dimensional Hirshfeld surface analysis, d_e and d_i are the distance from the point on the Hirshfeld surface to the closest nucleus outside and inside the surface, respectively. The Hirshfeld surface is mapped over the d_norm surface and it is based on d_e, d_i and vdW radii of the atoms. The d_norm plot is mapped with the red, blue and white color codes used for molecular contact analysis. The red and blue signify shorter and longer contacts than vdW and the white color designate contacts around the vdW radii.

2.8. Computational details

The Gaussian 09 software [26] was employed for all the calculations. XRD data is used for the starting structure for geometry optimizations. B3LYP functional [27, 28] with basis sets the 6-311G [29] is utilized for all elements. All the harmonic vibrational frequencies are found positive for all geometries which confirmed the correctness of the optimization results [30]. The electronic transition spectrum was calculated using the optimized structures. The results of these calculations will lead to further studies with the help of quantum chemistry parameters and we will compare all four complex structures. The molecular electrostatic potential (MEP) generated for the optimized structure explains the reactive sites present in the molecule. The negative potential associated with electrophilic reactivity is indicated by the red color and the positive potential indicating nucleophilic reactivity is represented by the blue color.

2.9. Molecular docking study

Molecular docking was done using AutoDock Vina software to further study the interaction of Zn(II), Mn(III) and Co(III) complexes with the target macromolecule in cancer treatment. The three-dimensional structure of the protein was downloaded from the Protein Databank (4LXD. PDB) website (http://www.rcsb.org./pdb). The optimal structure of the complexes was done using Gaussian 09 software and with the same B3LYP method, and it was docked to the target receptor. Also, the interaction between protein and ligand was determined using Discovery Studio 2020 client software.

3.1. Synthesis

Schiff base complexes were prepared from the reaction of ligand HL with methanolic solution containing metal salt with a ratio of 1:1 ZnBr₂.2H₂O (1), MnCl₂.2H₂O (2), and Co(OAc)₂.4H₂O (3). The complexes were identified using spectroscopic and crystallographic techniques. Also, they showed good elemental analysis. The electrochemical properties of the complexes indicate the electronic effects of the groups and the redox potential. Hirshfeld surface analysis was done to study and understand short contacts and non-covalent interactions, and with the help of graphic displays based on Hirshfeld surface analysis, d_i vs d_e mapped were also calculated. Furthermore, in this study, is discussed computational chemistry and molecular docking studies.

3.2. FT-IR spectra

In the FT-IR spectrum of the ligand, a strong peak in the region of 1627 cm^− 1 indicates the formation of the imine group (C = N). The observed peak in the 1438 region was attributed to the stretching vibration of the (C─N) group (Figure S1). According to the FT-IR spectrum of the Schiff base complexes in Figure S2, S3 and S4, it has a shift compared to the stretching vibration bands in the ligand, which confirms the synthesis of the complex. The stretching vibration band of the C = N group in these complexes was observed at a wave number lower than that of the ligand in the regions of 1618 (1, 2), 1616 (3), and 1606 (4) cm^− 1[14, 15]. The stretching vibration band in the regions of 1355 (1, 2), 1361 (3) and 1361 cm^− 1 (4) is attributed to the C─O band. Also, the observed shift of the complex (1–4) compared to the ligand is determined at 1461 (1, 2), 1454 (3) and 1436 cm^− 1 (4) corresponding to the stretching vibration of the C─N group. In addition,

metal-nitrogen and metal-oxygen absorption bands appeared in the regions of 421–580 cm^− 1 (1, 2), 481–572 cm^− 1 (3) and 414–524 cm^− 1 (4), respectively. The broad absorption band in the regions of 2760–3190 cm^− 1 was attributed to C─H stretching vibration [14, 15, 31–33].

Figures. S1-4.

3.3. UV–Vis spectra

In the electronic spectrum of the ligand, the three peaks at the wavelength of 306, 400 and 420 nm indicate the transitions (C = N) π → π* and n → π*(Fig.S5). The electronic spectrum of the collected complexes recorded in the acetonitrile solution and is shown in the Fig.S6-8. The absorption band observed in the complex (1–4) in the area 231 and 250 nm (1, 2), 230 and 249 nm (3), 208 and 231 nm (4) was attributed to the aromatic ring π → π*. Also, the absorption band appeared at 304 and 344 nm (1, 2), 306 and 330 nm (3), 275 and 322 nm (4) related to the transmission of intra -ligand (C = N), which has shifts compared to the ligand. The bands appeared in the area 403 and 418 nm (1, 2), 396 and 429 nm (3), 438 nm (4) are related to the charge transfer. For complexes (3, 4) in the 484 and 675 nm districts, d → d transfers was observed, respectively [13–15, 34–36].

Figures. S5-8.

3.4. Description of the crystal structures

Perspective views of the complexes are shown in Figs. 1–4; most important geometrical data are listed in Table 2. Interestingly, complexes display different coordination modes. Complex 1 of identical ZnL₂ composition is different, as it is unsymmetrical and the central ion is coordinated by three atoms from each L molecule (N₂O₃). It has to be noted, however that two additional Zn…O contacts are much longer than the other bonds. So, the coordination number in this case is six and the environment is slightly deformed octahedron. In this structure additionally, a solvent – methanol molecule was found, connected by hydrogen bond with O1A atom (O···O 2.721 Å, H···O 1.89 Å, O-H···O 172º). Complex 2, ZnL₂, is C₂-symmetrical (Zn ion lies on the twofold axis), and the central atom is coordinated by two oxygen and two nitrogen atoms (N₂O₂) from the ligand molecules in quite regular tetrahedral fashion.

Compound 3, Mn complex, has the MnL₂Cl structure and is again C₂-symmetrical (Mn and Cl atoms lie on the twofold axis). Mn is coordinated by two nitrogen atoms and two oxygen atoms from both L molecules and additionally by Cl, which occupies an apex of the tetragonal pyramid (c. n. 5). Finally, Co complex 4 has the composition CoL₃, one nitrogen and one oxygen atom from each ligand is involved in coordination which gives the coordination number 6 and octahedral geometry.

It might be noted that both the geometries of the ligand molecules and coordination schemes are quite typical for similar complexes. In the crystallographic database CSD there are 1727 structures of Zn complexes with c.n 4 and N₂O₂ coordination, 549 for Zn with c.n. 6 and N₂O₃, 92 for Mn with c.n. 5 and N₂O₂Cl and 1217 of Co, c.n. 6, N₃O₃.

Table 2

Relevant geometrical parameters (Å, º) with s.u.’s in parentheses
	1 (M = Zn)	2 (M = Zn)	3 (M = Mn)	4 (M = Co)
M1-O1A	1.992(4)	1.921(7)	1.852(2)	1.8837(15)
M1-N12A	1.993(5)	1.969(8)	2.045(3)	1.9341(17)
M1-O15A	2.451(4)
M1-O1B	1.961(4)	1.921(7)	1.852(2)	1.8905(14)
M1-N12B	1.992(5)	1.969(8)	2.045(3)	1.9359(17)
M1-O15B	2.546(4)
M1-O1C				1.9008(15)
M1-N12C				1.9395(17)
M1-Cl1			2.3890(16)
O1A-M1-N12A	90.50(18)	94.4(3)	87.38(10)
O1A-M1-O1B	105.61(18)	110.2(4)	170.19(17)	173.90(6)
O1A-M1-N12B	101.45(18)	120.9(3)	89.69(11)
N12A-M1-O1B	104.68(17)	120.9(3)	89.69(11)
N12A-M1-N12B	156.4(2)	117.9(5)	145.28(16)
O1B-Mn1-N12B	91.69(18)	94.4(3)	87.38(10)
O1A-M1-O15A	162.85(16)
O1A-M1-O15B	84.72(16)
N12A-M1-O15A	75.12(17)
N12A-M1-O15B	87.83(17)
O1B-M1-O15A	87.36(17)
O1B-M1-O15B	163.48(16)
N12B-M1-O15A	89.09(17)
N12B-M1-O15B	73.44(17)
O1A-M1-Cl1			94.91(8)
N12A-M1-Cl1			107.36(8)
O1B-M1-Cl1			94.91(8)
N12B-M1-Cl1			107.36(8)
O1C-Co1-N12B				175.58(7)
N12A-Co1-N12C				175.95(7)
C10-C11-N12-C13	174.9(5) 176.9(6)	176.7(9)	-171.0(3)	176.4(2) 178.9(2) -168.6(2)
C11-N12-C13-C14	134.7(5) 130.3(6)	-104.6(11)	87.5(4)	-81.9(2) 92.6(2) 80.7(2)
N12-C13-C14-O15	54.1(6) 56.7(7)	65.0(13)	-66.1(4)	62.9(2) -60.2(3) -69.5(3)
C13-C14-O15-C16	176.5(5) -178.2(6)	-172.3(12)	165.6(3)	171.75(19) 179.4(2) -78.1(3)

Figure. 1–4

Table 2

3.5. Electrochemical studies

Analysis of the electrochemical behavior of the synthesized complexes was recorded using cyclic voltammetry in DMSO solution. As shown in Figs. (5–7), the synthesized complexes (1–4) have shown irreversible behavior. In the cyclic voltammogram of the complex (1 and 2), a reduction process in the cathodic potential (Epc) was observed in the area of -1.16 and 0.219 V, and these areas are assigned to the reduction of Zn^II/I and Zn^I/0. According to Fig. 6 for complex (3), the cathodic voltagram observed at the potential of -0.84 and − 1.52 V indicates Mn^III/Mn^IІ and Mn^II/Mn^І. Cyclic voltammetry in Fig. 7 shows that in the cyclic voltammogram for complex (4), a decreasing voltammogram in cathodic potential (Epc) -0.531 and − 1.34 V caused by Co^Ш/Co^II and Co^II/Co^I has been observed. In addition, the redox process observed at the potential of 0.36 V is related to Co^II/Co^III oxidation [15, 37–39].

Figure. 5–7

3.6. Investigation of intermolecular interactions by HS analysis and FPs plot

The HSA facilitates visualization of the molecular component by permitting surface transparency via the use of d_norm, shape index, and fingerprint plots. The color code on Hirshfeld surfaces represents the geometrical function d_norm for complexes (1–4). The red patches on the d_norm surface denoted interatomic or shorter connections (< vdW radii). The graphics clearly show that the darker the color of the red region, the stronger the interactions, and the other shallower areas represent mostly the distribution of weaker the exchanges. The distribution of the approximate hydrogen bonding in the complexes may be evaluated using these figures, which is useful in further exploring the intrinsic aspects of the complex's stable existence.

3.6.1. HSA and FPs of the complex [Zn^II(HL)₂ CH₃OH] (1), [Zn^II(HL)₂] (2)

For complex [Zn^II(HL)₂CH₃OH] (1), the red spots obvious with d_norm revealed dominant interactions on the surface of O···O, C···H/H···C and O···H/H···O that contribute significantly to complex (1). Figure 8a, b labelled 1–14 observable red spots of 1 and 2 on account of two pairs of intermolecular C3A–H3A···O1C(number:1) and C5A–H5A···O1C(number:2) hydrogen bonds (labeled as a) whereas intermolecular H1C··· O1C (number:11) hydrogen bond (labeled as b), also, intermolecular C13D–H13D···C7B (No:3), C13D–H13D···C8B(No:4), C14A–H14A···C4B (No:9), C14A–H14A···C9B (No:10), C13C–H13C···C9A (No:13) and C14C–H14C···C7A(No:14) short contacts were indicated by light red spot (labeled as a, b) between one (C–H)_amine molecule and C atom of aromatic ring aldehyde. As well as, the C3B–H3B···C9A (No:6), C3B–H3B···C10A (No:7) and C8A–H8A···C5B (No:8) interactions via the (C–H)_{2−hydroxy 1−naphtaldehyde} group with C atoms of the 2-hydroxy 1-naphtaldehyde groups are apparent as the light zone on the Hirshfeld surface. The dark red spots on the Hirshfeld surface suggest predominant interatomic and shorter contacts (C1A…H1C, No:5). Moreover, the O1C…O1A (No:12) contact is involved between the (O)_{2−hydroxy 1−naphtaldehyde} atom of the complex and (O)_{MeOH solvent}. For complex [Zn^II(HL)₂] (2), the exchanges stronger, are identified with red on the Hirshfeld surface (Fig. 9a, b), which are recognizable to an interaction with C…C, C―H…C and C―H…O hydrogen bonds. The light red spots on the Hirshfeld surface shown C2…C16 (No:1), C8…C3 (No:2) (labeled as a) contacts between two the (C)_{2−hydroxy 1−naphtaldehyde} group with (C)_amine group (for No:1) and via two the (C)_{2−hydroxy 1−naphtaldehyde} group (for No:2). Furthermore, the light red spots on the surface indicated C6―H6…O15 (No:4) and H3―C3…C16B (No:5) interactions (labeled as a, b). In addition to the discussed short contacts, one of the dark red spots on the Hirshfeld surface indicates C13―H13A…O1 (No:3), (labeled as a, b) hydrogen bond between (O)_{2−hydroxy 1−naphtaldehyde} group and (C―H)_amine molecule.

Figures. 8–9

The shape index schemed on the Hirshfeld surface for complexes [Zn^II(HL)₂CH₃OH] (1) and [Zn^II(HL)₂] (2) molecules in Figs. 10(a, b) indicates that the aromatic ring (C…C) interactions between neighboring molecules labeled with number 1 on the shape index are blue- red bow-tie designs. Also seen in this figure, the “red π -holes”, which represent C—H··· π interactions, are labeled 2. These interactions are caused by C—H contacts with the center of the aromatic ring [22, 40].

Figures. 10

In order to better understand the contacts in the structure of the studied complexes, the fingerprint diagrams of FPs were examined (Figs. 11 and 12). In both complexes (1) and (2), it was shown that H...H contacts cover the most part of the fingerprint diagrams (54.5% and 53.6%) and with light colored parts from blue to blue-green, about d_e=d_i 1.1 to 1.8 Å for (1 and 2) it includes.

In addition to this contact, a pair of wings was observed in the FPs graphs, which was created by the combination of C...H/H...C contacts, and it made up about 35.7% and 32.3% for (1 and 2) of the surface of this graph. These combined contacts lead to the formation of C—H... π interactions (the shortest contacts were obtained with minimum values of d_i + d_e ≈2.6 and 2.8 Å). In addition, the two prongs observed in the diagram predict C—H⋯O hydrogen interactions in the structure of both complexes 1 and 2, which are formed by O⋯H contacts (number 3). This interaction occupies about 8.9% (for 1) and 11.3% (for 2) of the fingerprint diagram. C—H...O interactions have shown contact with minimum values of d_i + d_e < 1.2–2.6 Å (asymmetrically for 1) and 2.0 Å (symmetrically for 2). In the structure of these complexes, weaker contacts with a percentage of less than 2 are observed, contacts such as C...N(0.2%), O...N(0.2%), C...C (0.2%) and N...H (0.1%) cover the surface of the chart.

Figure. 11–12

3.6.2. HSA and FPs of the complex [(Mn^III(HL)₂) Cl](3)

The dark and light red areas appeared by d_norm function confirm several types of interactions and non-classical hydrogen interactions such as: C…C, C―H…C and C―H …Cl (Fig. 13). The C2...C17 (No:1) interaction between two neighboring carbon groups of the 2-hydroxy 1-naphthaldehyde ring and 2-ethoxyethylamine was seen as a bright red area on the Hirshfeld surface. In addition, the C4―H4…C11 (No:2) contact between the carbon molecule of the (C)_HC=N group and the carbon molecule of (C) _{2−hydroxy 1−naphthaldehyde} ring is revealed in the bright area. Furthermore, the dark red spot represents the C6-H6…Cl (No:3) hydrogen bond, which are formed by the interaction between the complex molecule with the (C)2_{− hydroxy 1−naphthaldehyde} atoms and with the (Cl) atom (Fig. 13).

Figure. 13

Similar to the [Zn^II(HL)₂CH₃OH] (1), [Zn^II(HL)₂] (2) complexes, the shape index confirms the presence of π…π (blue-red triangles) and C–H…π (red π-holes) interactions [22, 40], and is shown in Fig. 14.

Figure. 14

According to the calculation of the 2D diagrams in this complex, it can be understood that 93.1% of the total contact is made up of hydrogen atoms, which confirms the more important role of hydrogen atoms compared to others. Figure 15 shows the fingerprint diagram of complex (3), five types of H... interactions were calculated with different proportions: H...H (46.6% > H...C/H…C (33.6%) > H... O/O…H (8.9%) > H... Cl/Cl…H (1.9%) > H... N/N…H(1.8%). In this complex, similarly to [Zn^II(HL)₂CH₃OH] (1), [Zn^II(HL)₂] (2) complexes, the number 1 in the graphs shows H...H type contacts, and short contacts were calculated with values of d_i + d_e ≈ 2.2 Å. C...H/H...C (number 2) contacts are shown as wings in the graph. C—H... π interactions that formed the shortest contacts with minimum values of d_i + d_e ≈ 2.8 Å. Number 3, O...H/H…O contacts that shows C―H...O hydrogen bonds show (d_i + d_e ≈ 2.8 Å). Other weak intermolecular exchanges include less than 1.8% of C…C (0.9%) and Mn…H/H…Mn (0.3%) is formed.

Figure. 15

3.6.3. HSA and FPs of the complex [Co^III(HL)₃] (4)

By examining Fig. 16(a-c), the visible red spots on the Hirshfeld surface represent hydrogen bonds C—H…C, C—H…O, C…C, C…H and H…H in the [Co^III(HL)₃] complex (4). The bright red spots correspond to C7A—H7A…C8B (No:3), C7A—H7A…C9B (No:4) and C16C—H16C…C4B (No:8) interactions, these interactions are due to contact and proximity between (C—H) _{2−hydroxy 1−naphthaldehyde} with (C) _{2−hydroxy 1−naphthaldehyde} atom (for No:3 and 4) and via (C—H) _{2−ethoxyethylamine} with (C) _{2−hydroxy 1−naphthaldehyde} atom (for No:8), were observed. Also, the hydrogen interactions with bright red dots represent C14D—H14D…O15A (No:5), C2C—H2C…O15C (No:9) and C3C—H3C…O15C (No:10), which are caused by the contact of the (O) _{2−ethoxyethylamine} atom with (C-H)_{2−hydroxy 1−naphthaldehyde} (for No:9 and 10) and (C—H)_{2−ethoxyethylamine}(for No:5). In addition, the contacts H5A…H16C (No:1), C2A... C4C (No:2), H10B…H16F (No:6) and C2C…H16A (No:7) were observed in Figs. 16a, b. Stronger interactions with dark red dots include (No:6) formed through short proximity of (H)_{2−hydroxy 1−naphthaldehyde} and (H)_{2−ethoxyethylamine}. Weaker interactions with bright red dots on surface also confirm the short contacts between the carbon atom of 2-hydroxy-1-naphthaldehyde and (C)_{2−ethoxyethylamine} (for No:2), as well as, the carbon atom of 2-hydroxy-1-naphthaldehyde with (H)_{2−ethoxyethylamine} (No:7). More information about the interactions between dark and light red spots for all complexes is summarized in Table 3.

Table 3

Close contacts to be prominent in the complexes.
D―H...A		d(H...A) (Å)	d(D...A) (Å)	∠ (DHA) (°)
[Zn^II(HL)₂CH₃OH] (1)
C3A―H3A…O1C	0.949	2.575	3.441	151.76	(1)	light red spot
C5A―H5A…O1C	0.951	2.609	3.466	150.15	(2)	light red spot
C13D―H13D…C7B	0.950	2.733	2.650	94.96	(3)	light red spot
C13D―H13D…C8B	0.949	2.801	2.770	98.38	(4)	light red spot
C1A...H1C	-	2.787	-	-	(5)	dark red spot
C3B―H3B…C9A	0.951	2.728	3.604	153.50	(6)	light red spot
C3B―H3B…C10A	0.951	2.749	3.490	135.30	(7)	light red spot
H5B―C5B…H8A	0.950	2.740	2.829	96.50	(8)	light red spot
C14A―H14A…C4B	0.991	2.801	3.477	125.97	(9)	light red spot
C14A―H14A…C9B	0.991	2.826	3.731	152.21	(10)	light red spot
O1C...H1C	-	1.887	-	-	(11)	light red spot
O1A...O1C	-	-	2.721	-	(12)	light red spot
C14C―H14C…C7A	0.950	2.795	3.139	102.39	(13)	light red spot
C13C―H13C…C9A	0.990	2.764	3.588	140.97	(14)	light red spot
[Zn^II(HL)₂] (2)
C2…C16	-	-	3.329	-	(1)	light red spot
C3...C8	-	-	3.391	-	(2)	light red spot
C13―H13A…O1A	0.971	2.305	3.276	171.46	(3)	dark red spot
C6―H6…O15	0.930	2.626	3.375	138.00	(4)	light red spot
H3―C3...H16B	0.930	2.854	3.028	101.73	(5)	light red spot
[(Mn^III(HL)₂Cl] (3)
C2…C17	-	-	3.255	-	(1)	dark red spot
C4―H4…C11	0.930	2.847	3.638	143.66	(2)	light red spot
C6―H6…Cl	0.930	2.856	3.694	150.43	(3)	dark red spot
[Co^III(HL)₃] (4)
H5A…H16C	-	2.277	-	-	(1)	light red spot
C2A …C4C	-	-	3.380	-	(2)	light red spot
C7A―H7A…C8B	0.950	2.875	3.630	137.19	(3)	light red spot
C7A―H7A…C9B	0.950	2.777	3.584	143.28	(4)	light red spot
C14D―H14D…O15A	0.990	2.548	3.493	159.51	(5)	light red spot
H16F…H10B	-	2.102	-	-	(6)	dark red spot
C2C …H16A	-	-	3.235	-	(7)	light red spot
C16C―H16C…C4B	0.980	2.841	3.629	137.97	(8)	light red spot
C2C―H2C … O15C	0.950	2.647	3.258	122.57	(9)	light red spot
C3C―H3C … O15C	0.950	2.715	3.295	120.00	(10)	light red spot

Figures. 16

Table 3

Figure 17 shows a view of the Hirshfeld surface calculated by the shape index function. As it was predicted in this figure, similar to the studied complexes, the presence of π...π and C–H...π interactions with the special features of “blue- red triangle” (for π…π) and “red π-holes” (for C–H…π) were visible [22, 40].

Figure. 17

By studying the 2D fingerprint diagrams in Fig. 18, it was observed that the contribution of H···H exchange shown in the center of this diagram shows the greatest participation in the formation of the [Co^III(HL)₃] complex (4) (it occupies about 61.2% of the Hirshfeld surface). In this complex, C–H⋯π interactions arise from C⋯H/H…C contact C…H/H…C (No: 2) and occupy a part of this diagram, which is about 27.2% of the diagram. covers (d_i + d_e < 2.8). In addition, O···H/H····O (No: 3) contacts are observed in this complex (exchanges (8.2%) (d_i + d_e < 2.6)). In addition, several interactions with a lower ratio contribute to the stability of the crystal system, such as: (C...C (3.2%), N...H (0.1%) and C...O (0.1%) [22, 40].

More information obtained from the 2D fingerprint graph for all four crystal structures is summarized in Table 4.

Based on the results obtained from the 2D fingerprint graph it is deduced that more than one half of the surface corresponds to H…H contacts for all four complexes. Some of these contacts seem as a tip on the diagonal diagram providing short exchanges of H...H with values d_i + d_e < 2.2 Å, for all complexes, i.e. less than 2 × the van der Waals radius of hydrogen atoms. For all complexes, the H…O/O…H contribution covering strong C―H…O hydrogen bonds is marked by two sharp peaks providing the short contacts with the H…O/O…H distances less than the sum of the van der Waals radii of hydrogen and oxygen atoms (≈ 2.7 Å) including the values of d_i+ d_e ≈ 1.1–2.5 Å and 2 Å (for 1 and 2), 2.7 Å (for 3) and 2.5 Å (for 4). In complex (3), small spikes on the fingerprint graph can be seen which are associated to the H…Cl/Cl…H contacts related to the C―H…Cl hydrogen bond interactions. Some of these contacts provide the H…Cl/Cl…H short contacts with values of d_i+ d_e ≈ 2.7 Å, i.e. slightly less than the sum of the van der Waals radii of hydrogen and chlorine atoms (≈ 2.8 Å). In the case of the crystal structures, the study of the FPs displays that only three H...H, C…H/H…C and H...O/O...H interactions play an effective role in the crystal packing with significant contributions as have been discussed.

Table 4

The information obtained from the 2D fingerprint graph with a larger contribution interaction for the complexes.
Interactions	Percentage of participation	d_i	d_e		d_i+d_e
[Zn^II(HL)₂CH₃OH] (1)
H…H	54.5%	1.1–2.7	1.1–2.5		2.2
C…H	35.7%	1.6–2.7	1.6–2.5		2.6
O…H	8.9%	1.1–2.4	1.1–2.4		1.1–2.5
[Zn^II(HL)₂] (2)
H…H	53.6%	1.1–2.4	1.1–2.4		2.2
C…H	32.3%	1.7–2.5	1.7–2.4		2.8
O…H	11.3%	1.3–2.4	1.3–2.4		2.0
[(Mn^III(HL)₂Cl] (3)
H…H	46.6%	1.1–2.5	1.1–2.6		2.2
C…H	33.6%	1.7–2.5	1.7–2.6		2.8
O…H	8.9%	1.5–2.5	1.5–2.4	2.7
[Co^III(HL)₃] (4)
H…H	61.2%	0.9–2.6	0.9–2.6		1.8
C...H	27.2%	1.6–2.7	1.6–2.6		2.7
O…H	8.2%	1.4–2.5	1.4–2.5		2.5

Table 4

Figure. 18

3.7. Computational Chemistry and Density functional theory (DFT) calculations

3.7.1. UV-Vis spectrum ([Zn^II(HL)₂ CH₃OH] (1), [Zn^II(HL)₂] (2), [(Mn^III(HL)₂) Cl] (3) and [Co^III(HL)₃] (4) complexes)

electronic transitions of studied complexes 1 to 4 in acetonitrile solvent were calculated using computational chemistry at the B3LYP/6-311G level. The calculations performed using theoretical studies were compared with the experimental data of this spectrum (Figure S4 in the experimental section). In the electron transfer spectrum of experimental data, intra-ligand transfer (C = N) showed absorption bands in the region of 304–344, 306–330 and 275–322 nm for complexes (1, 2), (3) and (4), respectively. In comparison with the spectrum obtained from the theoretical studies, the same regions show a lower absorption band for complexes 1 to 2, 292–301 (for complex (1)) and 305–313 (for complex (2)), and a higher absorption band for complexes 3 to 4 around 371–387 (for complex (3)) and 384–423 (for complex (4)). Moreover, charge transfer is assigned in the regions of 403–418 nm (for complex (1, 2)) and 396–417 nm (for complex (3)). Computational chemistry electron transfer spectrum in this region, lower absorption band around 364–370 nm with energy transfer 3.419–3.277 eV (complex (1)), 359–373 nm with energy transfer 3.453–3.320 eV (complex (2)) and higher absorption band around 400–459 nm with energy transfer of 3.099–2.699 it was calculated. The d → d absorption band of the experimental spectrum of the complex (complex (3) and complex (4)) is around 484 and 675 nm and this electron transfer in computational chemistry has shown absorption bands at 760 and 605 nm with an energy transfer of 1.968 and 2.048 eV, respectively. According to the discussed results, it is concluded that computational chemistry correctly suggests the structure of all complexes. Also, the energy gap difference shows well the stability, hardness and reactivity of the complexes, the higher the energy gap difference, the higher the stability and chemical hardness and low reactivity of the complex [41, 42]. Therefore, for complex (1), the largest energy gap was calculated compared to other complexes ((2), (3)), as a result, this compound shows a higher chemical hardness, these results are further detailed in the analysis section and Frontier molecular orbital analysis will be discussed.

3.7.2. Frontier molecular orbital analysis

LUMO and HOMO molecular orbital images calculated at the B3LYP/6-311G level of theory for all four complexes 1 to 4 are shown in Fig. 19. The LUMO molecular orbitals in complexes (1 and 2) are mostly located on the naphthaldehyde ring, (O)_2−hydroxy atoms and HC = N atoms, while the HOMO orbitals are mainly distributed on the zinc metal, HC = N and contains very little naphthaldehyde rings. For complex (3) LUMO molecular orbitals, the coverage of the orbitals is mostly on the central metal Mn, HC = N and also covers a small part of the naphthaldehyde ring, but, for the HOMO orbitals has been seen on the naphthaldehyde ring, the central metal, HC = N and the group amine. For complex (4), the LUMO molecular orbitals are scattered on two ligands including the naphthaldehyde ring, (O)_2−hydroxy atoms and HC = N atoms and the metal center Co, but the HOMO orbitals are covered by one ligand and quantitative surface of naphtaldehyde rings, Co, HC = N.

In Table 5, the values of the calculated HOMO and LUMO energy levels for the complexes are respectively − 7.146 and − 5.747 eV for complex (1), -7.234 and − 5.782 eV for complex (2), -6.066 and − 5.449 eV for complex (3) and − 5.823 and − 5.514 eV for complex (4). Interesting results were collected by mapping frontier molecular orbitals (FMOs). The calculated LUMO values indicate the ability to accept electrons (nucleophilicity), while the obtained HOMO values determine the nature of the molecule to donate electrons (electrophilicity) [41, 43]. If the calculated LUMO energy value is lower, it indicates a high ability to accept electrons [41, 43]. By observing the results obtained in Table 5, it is concluded that complex (3) has the lowest LUMO energy compared to other complexes. Also, the energy difference (ΔE) of complex (4) is lower than complexes (1 > 2 > 3 > 4), as a result, metal ions as an active center has a stronger potential to accept electrons or it has electron donation. Therefore, the biological activity of the complexes was predicted as 4 > 3 > 2 > 1 [44]. According to the calculated energy of orbitals, it was used to check quantum parameters such as reactivity, electronegativity (χ), chemical potential (µ), chemical hardness (η), softness (S) [41, 45, 46]. The parameters were estimated using Eq. 5 − 1 respectively (Table 5).

E_GAP = E_LUMO - E_HOMO (1)

χ = -1/2(E_LUMO + E_HOMO) (2)

µ= - χ (3)

η = 1/2(E_LUMO − E_HOMO) (4)

S =\(\frac{1}{2{\eta }}\) (5)

The information related to the mentioned parameters for complexes 1 to 4 is presented in Table 5. The higher the energy difference between the HOMO and LUMO orbitals, the less polar and chemically reactive the molecule is, and it is referred to as a hard molecule, while the lower the energy difference between the orbitals, it is known as a soft molecule. According to the obtained information of these parameters, complex (2) with a higher energy gap, HOMO and LUMO, has a more stable structure than complexes (1), (3) and (4) and acts as a harder molecule. Complex (1) has a greater energy gap difference than (3), indicating that complex (1) is harder than (3). Complex (4) has a lower energy gap with more polarity and greater reactivity than complexes 1 to 3 (4 > 3 > 2 > 1, soft molecule).

Table 5. Calculated global reactivity descriptors of the three complexes at the B3LYP/6-311G level.
Parameters	Complex(1)		complex (2)	complex (3)	complex (4)
E_LUMO − E_HOMO (eV)		1.452	1.399	0.617	0.309
E_LUMO + E_HOMO (eV)		-12.893	-13.016	-11.515	-11.337
Electronegativity (χ)		6.5085	6.444	5.758	5.670
Chemical potential (µ)		-6.508	-6.444	-5.758	-5.670
Chemical hardness (η)	0.726	0.702	0.308	0.154
Softness (S)	0.688	0.712	1.620	3.243

Figure 19.

Table 5

3.7.3. Molecular electrostatic potential

One of the useful parameters for characterizing electrophilic and nucleophilic sites and hydrogen bonding exchanges is the molecular electrostatic potential (MEP) [47]. MEP maps are a visual representation of the electronic density for the title complexes, and these calculations are considered to relate the molecular structure to its physicochemical properties [48]. The 3D molecular electrostatic potential maps for the studied complexes are presented in Figs. 20, and the positive and negative locations of these complexes are colored with the electrostatic potential values increasing from red to blue. According to all four MEP schemes, it can be understood that oxygen atoms and Cl for complex (3) with red color have a negative electrostatic potential and strong repulsion and are candidates for electrophilic attack. The sites of strong attraction are the greatest possible regions with blue colors, which are observed near the C-H group, and central metal they provide highly reactive regions for nucleophilic attack. These locations are also presented for hydrogen bonding due to the existence of greatly electronegative atoms C, Cl and O. We were able to show the correctness of results MEP maps with the help of Hirshfeld surface analysis.

Figures 20.

3.8. Results from molecular docking studies

molecular docking was used to investigate the inhibitory potential of the [Zn^II(HL)₂CH₃OH] (1), [Zn^II(HL)₂] (2) [(Mn^III(HL)₂) Cl] (3) and [Co^III(HL)₃] (4) complexes to the target proteins (binding affinity to protein B-cell lymphorna (BCL-2, PDB ID: 4LXD)), which are important proteins involved in the cancer cell binding mechanism. By binding simulation, it was done by choosing the best state of the complexes towards the receptors with the highest negative binding energy. In this part, the interaction of complex (1–4) with an important molecular target in cancer treatment was done with the help of molecular simulation method [45, 46, 49–51]. By blocking ATP kinase, energy does not reach the cancer cells and this causes the cancer cells to die. Since cancer cells are able to absorb more energy, healthy cells receive less energy. Therefore, one of the inhibitory factors of cancer cells is ATP kinase, and in this section we used the PDB: 4LXD protein to study all four complexes [52, 53].

3.8.1. Results from molecular docking studies [Zn ^II (HL) ₂ CH ₃ OH] (1), [Zn ^II (HL) ₂ ] (2), [(Mn^III(HL)₂)Cl] (3) and [Co^III(HL)₃] (4) complexes

Two-dimensional and three-dimensional simulation models of the studied complexes are presented in Figs. 21–24 (a and b). First, the optimization of the studied structures was done, then, by performing the docking process, the complexes (1–4) were connected to the active site of the protein and the total energy of the system was calculated. In the case of the target protein 4LXD, the best ranking was obtained with a calculated total energy of the system − 27.48, -47.75, -64.66 and − 49.93 kcal/mol for complexes 1 to 4, respectively. By calculating the negative energies for the studied complexes, it is proved that the interaction of these complexes with 4LXD is able to disrupt the activity of this protein, therefore, these complexes can be suggested as inhibitors in cancer treatment. The results showed that the complexes 1 to 4 were able to create appropriate interactions with the active binding sites of proteins. Also, by forming various bonds, they showed that these structures inhibit the biochemical processes of protein 4LXD. As a result, the total system energy of complex (3) was lower than the total system energy of other studied complexes (1 < 2 < 4 < 3). In the Hirshfeld surface analysis study, complex (3) showed a different hydrogen bond due to the presence of chlorine atom in the structure compared to other complexes, due to this type of interaction in the crystal structure, molecular docking has shown a more favorable result. In addition, all the atoms described and involved in the intermolecular interactions of the Hirshfeld surface analysis are similarly involved in the molecular binding in the interaction between the protein and the receptor. The interaction of the active site amino acid of the receptor with the most potent inhibitor is briefly listed in Table 6 for all four complexes. In these complexes, proteins are able to penetrate well into the cavity of the active site of the receptors and cause the formation of more amino acids around the said complexes and cause non-covalent interactions and negative total energy of the system. Also due to the crystal structures of the complexes and the type of interaction in it and their favorable orientation in the active position of the receptors caused the formation of a favorable interaction with amino acids and increased the inhibitory power of this complex, complex (3) with the highest inhibitory activity against cancer protein (4LXD), with active amino acid residues the following interacted: PHE A:101,TYR A:105, ASP A:108, GLU A:142, ARG A:143, ALA A:146, PHE A:150, VAL A:153 and MET A:154, etc. through

Table 6. Amino acid interaction of the active site of the receptor with the strongest inhibitor.
Combined receptor		Total energy	Surrounding amino acids
[Zn^II (HL)₂CH₃OH] (1)
(ID: 4LXD)	-27.48	PHE A:101, TYR A:105, ASP A:108, PHE A:109, GLU A:111, MET A:112, SER A:113, VAL A:130, LEU A:134, ARG A:136, ARG A:143, ALA A:146, GLU A:149, PHE A:150, VAL A:153.
[Zn^II (HL)₂] (2)
(ID: 4LXD)	-47.75	PHE A:101, SER A:102, TYR A:105, ASP A:108, PHE A:109, MET A:112, SER A:113, GLU A:116, VAL A:130, LEU A:134, GLU A:142, ARG A:143, VAL A:145, ALA A: 146, PHE A:147, GLU A:149, PHE A:150, VAL A:153, MET A:154, GLU A:157.
[Mn^III (HL)₂Cl] (3)
(ID: 4LXD)	-64.66	PHE A:101, SER A:102, TYR A:105, ASP A:108, PHE A:109, MET A:112, VAL A:130, GLU A:133, LEU A:134, ASN A:140, GLU A:142, ARG A:143, ALA A: 146, GLU A:149, PHE A:150, VAL A:153, MET A:154.
[Co^III (HL)₃](4)
(ID: 4LXD)	-49.93	PHE A:101, SER A:102, TYR A:105, ARG A:106, ASP A:108, PHE A:109, GLU A:111, MET A:112, GLN A:115, VAL A:130, VAL A:131, LEU A:134, GLU A:142, ARG A:143, ALA A: 146, PHE A:147, GLU A:149, PHE A:150, VAL A:153.

Figures. 21–24

Table 6

In the present work, three new Zn(II), Mn(III), and Co(III) Schiff Base complexes were prepared by 2-hydroxy-1-(2-methoxyethylimino)-naphthalen (HL) and metal salts condensation reaction. The title complexes were identified by spectroscopic method and the structure of these complexes was determined by X-ray diffraction analysis. Also, the crystal structure is stabilized by short contacts and intermolecular hydrogen bonding of the C―H...O, C―H...C type, C―H... π and π···π stacking interactions, which results were also confirmed by Hirshfeld surface analysis. In addition, the parameters The optimized theoretical structure and the calculated results of HOMO/LUMO, MEP and UV-Vis studies are in good agreement with the experimental data. MEP calculations showed that oxygen and nitrogen atoms have high electronegativity with expected nucleophilic values. Elucidation of the activities of 4LXD protein drug targets for these newly synthesized complexes were discussed through molecular docking, the results showed that all four complexes can be recommended as suitable candidates for stronger biological activity.

Acknowledgements

We thank Semnan University for supporting this study.

Author contributions

SP & SR-did experimental, analysis and manuscript compilation with the supervision of MS. MS-directed, designed, gave insight and interpreted the spectroscopic data of the research project. MK-carried out the X-ray analysis of this project.

Availability of data and materials

All data generated or analyzed during this study are included in this published article. Data available in article supplementary material, the data that supports the findings of this study are available in the supplementary material of this article.

Funding

No funding

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Conflict of interest

The authors declare that they have no conflict of interest to disclose.

Hussain. Z, Yousif. E, Ahmed. A, Altaie. A, Synthesis and characterization of Schiff's bases of sulfamethoxazole, Org Med Chem Lett, 2014,28;4(1):1. DOI: 10.1186/2191-2858-4-1
Arulmurugan. S, Kavitha. H.P, Venkatraman. B.R, Biological activities of Schiff base and its complexes: A review, Rasayan J Chem, 2010,3, 385–410.
Mahmoud. W.H, Deghadi. R.G, Mohamed. G.G, Novel Schiff base ligand and its metal complexes with some transition elements. Synthesis, spectroscopic, thermal analysis, antimicrobial and in vitro anticancer activity, Appl Organometal Chem, 2016,30(4), 221–230. https://doi.org/10.1002/aoc.3420.
Kareem. M.J, Al-Hamdani. A.A.S, Jirjees. V.Y, Khan. M.E, Allaf. A. W, Zoubi. W. Al, Preparation, spectroscopic study of Schiff base derived from dopamine and metal Ni (II), Pd (II), and Pt (IV) complexes, and activity determination as antioxidants, J. Phys. Org. Chem., 2021,34(3), 4156. https://doi.org/10.1002/poc.4156.
Rezaeivala M., Keypour H, Schiff base and non-Schiff base macrocyclic ligands and complexes incorporating the pyridine moiety–The first 50 years, Coord. Chem. Rev. 2014,280, 203–253.https://doi.org/10.1016/j.ccr.2014.06.007.
Lu. A, Salabas, E.L., Schuth, F., Angewanted Chemistry International Edition. 2007, 46, 1222 – 1244. https://doi.org/10.1002/anie.200602866.
Poulter. N, Donaldson. M, Mulley. G, Duque. L, Waterfield. N, Shard. A.G, Spencer. S., Tobias. A, Jenkins. A, Johnson. A.L, Plasma deposited metal Schiff-base compounds as antimicrobials, New J. Chem. 2011, 35, 1477-1484. https://doi.org/10.1039/C1NJ20091G.
Majumder. S, Bhattacharya. A, Naskar. J.P, Mitra. P, Chowdhury. S, An oxorhenium(V) Schiff-base complex: Synthesis, characterisation, structure, spectroscopic and electrochemical aspects, Inorg. Chim. Acta. 2013, 399, 166-171. https://doi.org/10.1016/j.ica.2013.01.018.
Deilami. A.B, Salehi. M., Arab. A., Amiri. A, Synthesis, crystal structure, electrochemical properties and DFT calculations of three new Zn(II), Ni(II) and Co(III) complexes based on 5-bromo-2-((allylimino)methyl) phenol Schiff-based ligand, Inorg. Chim. Acta. 2018, 476, 93-100. https://doi.org/10.1016/j.ica.2018.02.013.
Kadhiravansivasamy. K, Sivajiganesan. S, Periyathambi. T, Nandhakumar. V, Chidhambram. S, Manimekalai. R, Synthesis and Characterization of Schiff Base CoII, NiII and CuII Complexes, Derived from 2-Hydroxy-1-naphthaldehyde and 2-Picolylamine, Mod Chem appl. 2017, 5,1. DOI: 10.4172/2329-6798.1000197.
Mahendra Raj. K, Vivekanand. B, Nagesh. G.Y, Mruthyunjayaswamy. B.H.M, Synthesis, spectroscopic characterization, electrochemistry and biological evaluation of some binuclear transition metal complexes of bicompartmental ONO donor ligands containing benzo[b]thiophene moiety, J. Mol. Struct., 2014, 1059, 280-293. https://doi.org/10.1016/j.molstruc.2013.12.010.
Mapari. A.K, Mangaonkar. K.V, Synthesis, characterization and antimicrobial activity of mixed Schiff base ligand complexes of transition metal (II) ions, Int. J. Chem Tech Res., 2011, 3(1), 477-482.
Kazemi. Z, Rudbari. H. A, Sahihi. M., Mirkhani. V, Moghadam. M, Tangestaninejad. S, Gharaghani. S, Synthesis, characterization and biological application of four novel metal-Schiff base complexes derived from allylamine and their interactions with human serum albumin: Experimental, molecular docking and ONIOM computational study, Journal of Photochemistry and Photobiology B: Biology., 2016, 162, 448-462. https://doi.org/10.1016/j.jphotobiol.2016.07.003.
Abbasi. Z, Salehi. M, Khaleghian. A, Kubicki. M, In vitro cytotoxic activity of a novel Schiff base ligand derived from 2-hydroxy-1-naphthaldehyde and its mononuclear metal complexes, J. Mol. Struct., 2018, 1173, 213-220. https://doi.org/10.1016/j.molstruc.2018.06.104.
Ramezanipoor. S, Parvarinezhad. S, Salehi. M, Grześkiewicz. A. M, Kubicki. M, Crystal structures, electrochemical properties and theoretical studies of three New Zn(II), Mn(III) and Co(III) Schiff base complexes derived from 2-hydroxy-1-allyliminomethyl-naphthalen, J. Mol. Struct., 2022, 1257(1), 132541. DOI: 10.1016/j.molstruc.2022.132541.
Chowdhury. D. A, Uddin. M. N, Hoque. F, Dioxouranium(VI) Complexes of Some Bivalent Tridentate Schiff-base Ligands Containing ONS Donor Set, Chiang Mai J. Sci., 2010, 37(3), 443-450.
O.D. Rigaku CrysAlisPro 1.171.38.34a. 2015.
Altomare. A, Cascarano. G, Giacovazzo. C, Guagliardi. A, Completion and refinement of crystal structures with SIR92, J. Appl. Crystallogr., 1993, 26, 343-350. https://doi.org/10.1107/S0021889892010331.
Sheldrick. G. M, SHELXT – Integrated space-group and crystal-structure determination, Acta Crystallogr, 2015, C71, 3-8. http://dx.doi.org/10.1107/S2053229614024218.
Seth. SK, Sarkar. D, Kar. T, Use of π–π forces to steer the assembly of chromone derivatives into hydrogen bonded supramolecular layers: crystal structures and Hirshfeld surface analyses, CrystEngComm., 2011, 13, 4528–4535. https://doi.org/10.1039/C1CE05037K.
Seth. SK, Sarkar. D, Royd. A, Kar. T, Insight into supramolecular self-assembly directed by weak interactions in acetophenone derivatives: crystal structures and Hirshfeld surface analyses, CrystEngComm., 2011, 13, 6728–6741. https://doi.org/10.1039/C1CE05670K.
Parvarinezhad. S, Salehi. M, Synthesis, characterization, crystal structures, Hirshfeld surface analysis and DFT computational studies of new Schiff Bases derived from Phenylhydrazine, J. Mol. Struct., 2020, 1222(1),128780. https://doi.org/10.1016/j.molstruc.2020.128780.
Sepehrfar. S, Salehi. M, Parvarinezhad. S, Grześkiewicz. AM, Kubicki. M, New Cu(II), Mn(II) and Mn(III) Schiff base complexes cause noncovalent interactions: X-ray crystallography survey, Hirshfeld surface analysis and molecular simulation investigation against SARS-CoV-2, J Mol Struct.,2023, 15;1278, 134857. doi: 10.1016/j.molstruc.2022.134857.
Turner. M.J, McKinnon. J.J, Wolff. S.K, Grimwood. D.J, Spackman. P.R, Jayatilaka. D, Spackman. M.A, CrystalExplorer17, University of Western Australia, 2017.
Seth. SK, Exploration of supramolecular layer and bi-layer architecture in M(II)–PPP complexes: Structural elucidation and Hirshfeld surface analysis [PPP = 4-(3-Phenylpropyl) pyridine, M = Cu(II), Ni(II)], J. Mol. Struct., 2014, 1070, 65-74. https://doi.org/10.1016/j.molstruc.2014.04.045.
Frisch, M. J., G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani et al. Gaussian 09 Revision A. 1, 2009.
Lee. C, Yang. W, Parr. RG, Development of the Colle-Salvetti correlation-energy formulainto a functional of the electron density, Phys. Rev. B, 1988, 37, 785–789. DOI:https://doi.org/10.1103/PhysRevB.37.785.
Becke. AD, Density-Functional Thermochemistry. III. The Role of Exact Exchange, Chem. Phys., 1993, 98, 5648-5652.http://dx.doi.org/10.1063/1.464913.
Parvarinezhad. S, Salehi. M, Kubicki. M, Khaleghian. A, Unprecedented formation of a μ-oxobridged dimeric copper (II) complex: Evaluation of structural, spectroscopic, and electronic properties by using theoretical studies and investigations biological activity studies of new Schiff bases derived from pyrazolone, Appl. Organomet. Chem., 2021, 6443,1090-1103. DOI: 10.1002/aoc.6443.
Gordon. MS, Fedorov. DG, Pruitt. SR., Slipchenko. LV, Fragmentation Methods: A Route to Accurate Calculations on Large Systems, Chem. Rev., 2012, 112, 632−672. https://doi.org/10.1021/cr200093j.
Abu-Dief. A.M. Mohamed. I.M, A review on versatile applications of transition metal complexes incorporating Schiff bases, Beni Suef Univ J Basic Appl Sci., 2015, 4(2),119-133. https://doi.org/10.1016/j.bjbas.2015.05.004.
Adão. P, Costa Pessoa. J, Henriques. R.T, Kuznetsov. M.L, Maurya. F.A, Kumar. M.R, Correia. U & I, Synthesis, characterization, and application of vanadium− salan complexes in oxygen transfer reactions, Inorg. Chem., 2009, 48, 3542-3561. https://doi.org/10.1021/ic8017985.
Correia, I., Costa Pessoa, J., Duarte, M.T., Henriques, R.T., Piedade, M.F.M., Veiros, L.F., Jakusch, T., Kiss, T., Dörnyei, Á., Castro, M.M.C. and Geraldes, C.F., N′‐Ethylenebis (pyridoxylideneiminato) and N, N′‐Ethylenebis (pyridoxylaminato): Synthesis, Characterization, Potentiometric, Spectroscopic, and DFT Studies of Their Vanadium (IV) and Vanadium (V) Complexes, Eur. J., 2004, 10, 2301-2317. https://doi.org/10.1002/chem.200305317.
Abbasi. Z, Salehi. M, Kubicki. M, Khaleghian. A, New Ni(II) complexes involving symmetrical bidentate N, O-donor Schiff base ligands: synthesis at ambient temperature, crystal structures, electrochemical study, antioxidant and cytotoxic activities, J. Coord. Chem., 2017, 70(18), 3132-3146. https://doi.org/10.1080/00958972.2017.1373189.
Holden Thorp. H, Electrochemistry: Applications in Inorganic Chemistry Based in part on the article Electrochemistry: Applications in Inorganic Chemistry by Robert H. Crabtree which appeared in the Encyclopedia of Inorganic Chemistry, First Edition, Encyclopedia of Inorganic Chemistry., 2006. https://doi.org/10.1002/0470862106.ia067.
Prakash. A, Adhikari. D, Application of Schiff bases and their metal complexes-A Review, Int. J. Chem. Tech. Res., 2011, 3(4), 1891-1896.
Chaudhari. U.K, Bharti. A, Nath. P, Azad. U.P, Prakash. R, Butcher. R.J, Bharty. M.K, Synthesis, structure, photoluminescence and electrochemical properties of mononuclear Ag(I) and polymeric Zn(II) complexes of potassium 4-methyl piperazine-1-carbodithioate, J. Mol. Struct., 2019, 1177, 260-268. DOI: 10.1016/J.Molstruc.2018.09.055
Naskar. S, Biswas. S, Mishra. D, Adhikary. B, Falvello. L, Soler. T, Schwalbe. C, Chattopadhyay. S , Studies on the relative stabilities of Mn (II) and Mn (III) in complexes with N₄O₂ donor environments: crystal structures of [Mn (pybzhz) ₂] and [Mn (Ophsal)(imzH) ₂] ClO₄ (pybzhz= N-(benzoyl)-N′-(picolinylidene) hydrazine, Ophsal= N, N′-o-phenylenebis (salicylideneimine), imzH= imidazole), Inorg. Chem. Acta., 2004, 357, 4257-4264. https://doi.org/10.1016/j.ica.2004.06.018.
Böttcher. A, Takeuchi. T, Hardcastle. K. I, Meade. T. J, Gray. H. B, Cwikel. D, Dori. Z, Spectroscopy and Electrochemistry of Cobalt(III) Schiff Base Complexes, Inorg. Chem., 1997, 36(12), 2498-2504. doi:10.1021/ic961146v.
Parvarinezhad. S, Salehi. M, Kademinia. Sh, Kubicki. M, The structural study, Hirshfeld surface analysis, and DFT calculations of ferrocenyl-hydrazine Schiff base: A novel precursor for the selective preparation of Fe₂O₃ nanoparticles, J. Mol. Struc., 2019, 1197, 96e107. https://doi.org/10.1016/j.molstruc.2019.06.109.
Parvarinezhad. S, Salehi. M, Kubicki. M, Eshaghi Malekshah. R, Experimental and theoretical studies of new Co(III) complexes of hydrazide derivatives proposed as multi-target inhibitors of SARS-CoV-2, Appl. Organomet. Chem., 2022,36, e6836. https://doi.org/10.1002/aoc.6836.
Parvarinezhad. S, Salehi. M, Synthesis, characterization, anti-proliferative activity and Chemistry computation of DFT theoretical methods of hydrazine-based Schiff bases derived from methyl acetoacetate and α-hydroxyacetophenone, J. Mol. Struct., 2020, 1225, 129086. DOI: 10.1016/j.molstruc.2020.129086.
(a) Venkatesh. N, Naveen. B, Venugopal. A, Suresh. G, Mahipal. V, Manojkumar. P, Parthasarathy. T, Donor-acceptor complex of 1-benzoylpiperazine with p-chloranil: Synthesis, spectroscopic, thermodynamic and computational DFT gas phase/PCM analysis, J. Mol. Struct. 2019, 1196, 462–477. https://doi.org/10.1016/j.molstruc.2019.06.083; (b) Xu. L.Y, Chai. Y.M., Li. C.G, Chai. L.Q, Co (II) and Cd (II) complexes with imidazole‐2‐carboxaldehyde groups: spectroscopic, antibacterial, Hirshfeld surfaces analyses, and TD/DFT calculations, Appl.Organomet. Chem., 2021, 35(8), 6279. https://doi.org/10.1002/aoc.6279.
Zhou. Y.H, Liu. X.W, Chen. L.Q, Wang. S.Q, Cheng. Y, Synthesis, structure and superoxide dismutase-like activity of two mixed-ligand Cu (II) complexes with N, N′-bis (2-pyridylmethyl) amantadine, Polyhedron, 2016, 117, 788–794. https://doi.org/10.1016/j.poly.2016.07.027.
Parvarinezhad. S, Salehi. M, Malekshah. R.E, Kubicki. M, Khaleghian. A, Synthesis, characterization, spectral studies two new transition metal complexes derived from pyrazolone by theoretical studies, and investigate anti-proliferative activity, Appl. Organomet. Chem., 2022, e6563. https://doi.org/10.1002/aoc.6563.
Parvarinezhad. S, Salehi. M, Kubicki. M, Malekshah. R.E, Synthesis, characterization, spectral studies and evaluation of noncovalent interactions in co-crystal of μ-oxobridged polymeric copper(II) complex derived from pyrazolone by theoretical studies, J. Mol. Struct., 2022, 1260(5), 132780. DOI: 10.1016/j.molstruc.2022.132780.
Pullman. B, Quantum-mechanical approach to the conformational basis of molecular pharmacology, Adv. Quantum Chem., 1977, 10, 251–328. https://doi.org/10.1016/S0065-3276(08)60582-1.
Szafran. M, Komasa. A, Bartoszak-Adamska. E, Crystal and molecular structure of 4-carboxypiperidinium chloride (4-piperidinecarboxylic acid hydrochloride), J. Mol. Struct., 2007, 827, 101–107. https://doi.org/10.1016/j.molstruc.2006.05.012.
Abdelwahab. H.E, Hassan. S.Y, Yacout. G.A, Mostafa. M.A, Sadek. M.M. El, Synthesis and biological evaluation of new imine-and amino-chitosan derivatives, Polymers., 2015, 7, 2690-2700. https://doi.org/10.3390/polym7121532.
Chen. Y.Z, Ung. C. Y, Computer automated prediction of potential therapeutic and toxicity protein targets of bioactive compounds from Chinese medicinal plants, Am. J. Chin. Med., 2002, 30, 139-154. https://doi.org/10.1142/S0192415X02000156.
Prasad. C, Rao. A. V, Rao. M. V, Computer aided design and molecular docking studies on a series of 1,3-thiazolidine-2,4-diones as new class of 5-lipoxygenase inhibitors, Journal of Pharmacy Research, 2014,8(6), 858-863.
Sivaramakarthikeyan. R, Iniyaval. Sh, Saravanan. V, Lim. W-M, Mai. Ch-W, Ramalingan. Ch, Molecular Hybrids Integrated with Benzimidazole and Pyrazole Structural Motifs: Design, Synthesis, Biological Evaluation, and Molecular Docking Studies, ACS Omega. 2020,5, 10089−10098. https://doi.org/10.1021/acsomega.0c00630.
Abd El-Karim. S. S, Anwar. M. M, Mohamed. N. A, Nasr. T, Elseginy. S. A, Design, synthesis, biological evaluation and molecular docking studies of novel benzofuran–pyrazole derivatives as anticancer agents, Bioorg. Chem. 2015, 63, 1-12. https://doi.org/10.1016/j.bioorg.2015.08.006.

No competing interests reported.

Synthesis, spectra, crystal structure, Hirshfeld surface analysis, DFT calculations and molecular docking evaluation on novel mononuclearZn(II), Mn(III) and Co(III) Schiff base complexes derived from 2- hydroxy-1-naphthaldehyde

Status:

Version 1

Abstract

Figures

1. Introduction

2. Experimental section

2.1. Materials and methods

2.2. Synthesis of [Zn^II(HL)₂ CH₃OH] (1), [Zn^II(HL)₂] (2)

2.3. Synthesis of [Mn^III(HL)₂ Cl] (3)

2.4. Synthesis of [Co^III(HL)₃] (4)

2.5. X-ray single crystal data collection and refinement

2. 6. Cyclic voltammetry

2. 7. Hirshfeld surface analysis

2.8. Computational details

2.9. Molecular docking study

3. Results and discussion

3.1. Synthesis

3.2. FT-IR spectra

3.3. UV–Vis spectra

3.4. Description of the crystal structures

3.5. Electrochemical studies

3.6. Investigation of intermolecular interactions by HS analysis and FPs plot

3.6.1. HSA and FPs of the complex [Zn^II(HL)₂ CH₃OH] (1), [Zn^II(HL)₂] (2)

3.6.2. HSA and FPs of the complex [(Mn^III(HL)₂) Cl](3)

3.6.3. HSA and FPs of the complex [Co^III(HL)₃] (4)

3.7. Computational Chemistry and Density functional theory (DFT) calculations

3.7.1. UV-Vis spectrum ([Zn^II(HL)₂ CH₃OH] (1), [Zn^II(HL)₂] (2), [(Mn^III(HL)₂) Cl] (3) and [Co^III(HL)₃] (4) complexes)

3.7.2. Frontier molecular orbital analysis

3.7.3. Molecular electrostatic potential

3.8. Results from molecular docking studies

4. Conclusion

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1

Synthesis, spectra, crystal structure, Hirshfeld surface analysis, DFT calculations and molecular docking evaluation on novel mononuclearZn(II), Mn(III) and Co(III) Schiff base complexes derived from 2- hydroxy-1-naphthaldehyde

Status:

Version 1

Abstract

Figures

1. Introduction

2. Experimental section

2.1. Materials and methods

2.2. Synthesis of [ZnII(HL)2 CH3OH] (1), [ZnII(HL)2] (2)

2.3. Synthesis of [MnIII(HL)2 Cl] (3)

2.4. Synthesis of [CoIII(HL)3] (4)

2.5. X-ray single crystal data collection and refinement

2. 6. Cyclic voltammetry

2. 7. Hirshfeld surface analysis

2.8. Computational details

2.9. Molecular docking study

3. Results and discussion

3.1. Synthesis

3.2. FT-IR spectra

3.3. UV–Vis spectra

3.4. Description of the crystal structures

3.5. Electrochemical studies

3.6. Investigation of intermolecular interactions by HS analysis and FPs plot

3.6.1. HSA and FPs of the complex [ZnII(HL)2 CH3OH] (1), [ZnII(HL)2] (2)

3.6.2. HSA and FPs of the complex [(MnIII(HL)2) Cl](3)

3.6.3. HSA and FPs of the complex [CoIII(HL)3] (4)

3.7. Computational Chemistry and Density functional theory (DFT) calculations

3.7.1. UV-Vis spectrum ([ZnII(HL)2 CH3OH] (1), [ZnII(HL)2] (2), [(MnIII(HL)2) Cl] (3) and [CoIII(HL)3] (4) complexes)

3.7.2. Frontier molecular orbital analysis

3.7.3. Molecular electrostatic potential

3.8. Results from molecular docking studies

4. Conclusion

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1

2.2. Synthesis of [Zn^II(HL)₂ CH₃OH] (1), [Zn^II(HL)₂] (2)

2.3. Synthesis of [Mn^III(HL)₂ Cl] (3)

2.4. Synthesis of [Co^III(HL)₃] (4)

3.6.1. HSA and FPs of the complex [Zn^II(HL)₂ CH₃OH] (1), [Zn^II(HL)₂] (2)

3.6.2. HSA and FPs of the complex [(Mn^III(HL)₂) Cl](3)

3.6.3. HSA and FPs of the complex [Co^III(HL)₃] (4)

3.7.1. UV-Vis spectrum ([Zn^II(HL)₂ CH₃OH] (1), [Zn^II(HL)₂] (2), [(Mn^III(HL)₂) Cl] (3) and [Co^III(HL)₃] (4) complexes)