Synthesis, Characterisation, DFT Study and Biological Evaluation of Complexes Derived from Transition Metal and Mixed Ligands

Abstract

This research prepared and characterised novel mixed coordination complexes derived from escitalopram with eugenol and curcumin to form (L₁) and (L₂), respectively. The complexes were prepared via Williamson ether synthesis and analysed by FTIR, UV–Vis, ¹H-NMR spectroscopy, elemental analysis, molar conductivity, and magnetic susceptibility. The results confirmed their octahedral geometries. Magnetic investigation reported high-spin configurations for Mn(II), Co(II), and Ni(II) complexes, whereas Cu(II) exhibited a distorted octahedral arrangement with characteristic d–d transitions. In addition, the calculation of Density functional theory (DFT) provided more insight into the detailed structural and electronic properties of the new ligand and its complexes. Antimicrobial compounds were evaluated against Escherichia coli, Staphylococcus aureus, and Candida albicans through the agar well diffusion method. The reported results revealed that Cobalt complexes showed antimicrobial activity followed by Copper (Cu), Nickel (Ni) and Manganese(Mn) complexes, respectively, due to an increase in Co-lipophilicity, which leads to improved diffusion through microbial cell membranes. The research findings confirmed that escitalopram-based mixed ligands coordinate with transition metals and could have significant biological applications.

1. Introduction

Recently, coordination complexes that involve biologically active ligands have been highlighted in much research due to their potential therapeutic applications. Eugenol, Escitalopram, and Curcumin have enormous interstitial medical applications, such as antidepressant, antioxidant, reducing heart diseases, anti-inflammatory, antimicrobial properties, reducing pain and anticancer factor. Furthermore, they have interesting antibacterial effects [1,2,3,4,5].

Eugenol (Eug) is a phenolic compound that has an allylchain-substituted guaiacol and belongs to the phenylpropanoid chemical compound family. It is a colourless to pale yellow oil. It is simply extracted from plant leaves. The polyphenol (eugenol) can damage the membranes of negative and positive Gram bacteria due to its antibacterial properties [6]. Eugenol is a bidentate ligand recently applied in coordination chemistry with some transition metal elements (Figure 1a). Then the resulting complexes exhibited valuable bacterial activities [7]. At the same time, escitalopram (Esc) is classified under the medical class Selective Serotonin Reuptake Inhibitor (SSRI). Its Core chemical structure has phenylbutylamine, a nitrile group and a dihydrobenzofuran ring. It can be chemically linked to form multifunctional ligands with chelating ability [8] (Figure 1b).

Finally, Curcumin (Cur) (diferuloylmethane) is a natural hydrophobic polyphenol derived from turmeric powder of Curcuma longa. It has been extensively investigated for pharmacological and biological effects. Curcumin can form strong complexes with most of the central transition metal ions through the enolic group [9] (Figure 1c).

Transition metals like Mn(II), Cu(II), Zn(II), Fe(II) and Co(II) could form a stable coordination bond with Eug, Cur and Esc through the N atom in amine or amide, O atom related to O in β-diketone moiety and/or phenolic oxygen. This new modulation of electronic properties can potentially enhance therapeutic efficacy [10]. In addition, some theoretical studies noted that these types of ligands have effective roles against advanced viruses such as COVID-19 [11], especially when these ligands can be mixed together.

To the best of our knowledge, there is no study that examines yet the effect of mixed Eug_Esc or Cur_Esc mixed ligand complexes against some types of bacteria, such as Gram-positive, which is Staphylococcus aureus type and Gram-negative, like E. coli. The mixed Eug_Esc and Cur_Esc mixed ligands were prepared via Williamson ether synthesis. The ligand and complexes were characterised by FTIR and ¹HNMR spectroscopy and Uv-vis absorbance. The molar conductivity of complexes was tested in DMSO solvent. Carbon(C), hydrogen(H), nitrogen(N) and central ion quantities were also investigated. The resulting complexes showed octahedral geometry. All complexes reported very high activity towards these types of bacteria.

2. Materials and Methods

2.1. Material and Measurement Technique

All chemical compound; manganese Chloride(MnCl₂·5H₂O), Cobalt Chloride (CoCl₂·6H₂O), Nickel Chloride(NiCl₂·6H₂O) Copper chloride(CuCl₂·2H₂O), Absolute Ethanol(Etol), Dimethyl sulfoxide (DMSO), Chloroform (CCl₄), Eugenol (4-Allyl-2-methoxyphenol), Escitalopram ((S)-1-[3-(Dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro isobenzofuran-5-carbonitrile) and Curcumin 1E,6E)-1,7-bis (4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione were provided either from Merck or Fluka compony (Darmstadt, Germany) without further purification.

A Fourier-transform infrared (FTIR) spectra Module 8300 Shimadzu spectrophotometer (Kyoto, Japan) was utilised to examine the prepared mixed ligands and complexes using caesium iodide discs. The transmitted absorbance of samples was measured using an Ultraviolet light-visible (Uv-vis) spectrophotometer module 1600 Shimadzu (Kyoto, Japan). in the range of (200–800 nm). To determine the melting point (MP) of the prepared complexes, a digital display MP temperature Stuart apparatus module SMP30 (Staffordshire, UK)was used. For electrical molar conductivity measurements of complexes, they were carried out at room temperature (25 °C) using a 4510–Jenway in (10^–3 mol·L^–1) DMF solution. Bruker Bio Spin GmbH, 400 MHz, (Rheinstetten, Germany) was used to determine ¹H NMR spectra of complexes using tetramethylsilane as internal reference solvent, while the chemical shifts were quoted in δ (ppm). Atomic absorption module SensAA (Melbourne, Australia) was utilised to determine central metal ions (Mn(II), Ni(II), Co(II) and Cu(II). While the effective magnetic moments measured by MSB MK1 Sherwood (Cambridge, UK).

2.2. Preparation of the Mixed Escitalopram and Clove Oil (Eugenol) (Esc-Eug) Ligand

The cyclic (Esc-Eug) ligand was prepared through Williamson Ether Synthesis [12,13,14] by reacting 0.01 M (equivalent to 3.24 g) escitalopram with Eugenol (0.01 M (equivalent to 1.64 g). The chemical reaction was carried out in a 100 mL round-bottom flask. Chloroform was used as a solvent in a basic medium (commonly using bases like NaOH or K₂CO₃). The chemical mixture was then refluxed for 8 h under continuous stirring to ensure the reaction completion and ether formation. At the end of refluxing, the resulting precipitate was then filtered, washed, and dried thoroughly. And recrystallised with ethanol to purify the product. Scheme 1 shows the chemical mechanism of cyclic ether formation.

2.3. Preparation of the Mixed Escitalopram and Curcumin (Esc_Cur) Ligand

The cyclic (Esc_Cur) ligand was prepared through Williamson Ether Synthesis, similar to Section 2.2, by reacting 0.01 M (equivalent to 3.24 g) escitalopram with Curcumin (0.01 M (equivalent to 3.68 g). The final precipitate was then filtered, washed, and dried thoroughly and recrystallised with ethanol to purify the product. The Scheme 2 shows the chemistry of cyclic ether formation.

2.4. General Preparation of the Mixed Ligand-Transition Metal Complexes

Solutions of the metal chlorides (0.01 M) like MnCl₂·5H₂O, CoCl₂·6H₂O, NiCl₂·6H₂O and CuCl₂·2H₂O were mixed with an equivalent molar amount (0.01 M) of the prepared ligand in Section 2.2 or Section 2.3 using chloroform as solvent. The reaction mixture was then refluxed for 4 h to ensure the formation of transition metal complexes. At the end of refluxing, the formed precipitates were then collected by drying and recrystallised using ethanol to obtain purified crystalline complexes.

3. Results and Discussion

3.1. Fourier Transfer Infrared Spectroscopy (FTIR)

As shown in Figure 2. The ligand (L₁) exhibits peaks at (3339) cm⁻¹ that belong to the ν(N-H) bond stretching. Other peaks at (3061, 3028) are attributed to the ν(C-H) aromatic stretch. While Aliphatic ν(C-H) stretching peaks appeared at (2913, 2853, 2806) cm⁻¹, respectively.

The Peaks at (1640, 1589, 1556) (cm⁻¹) belong to aromatic ν(C=C) and ν(N-H) bending. ν(CH₂/CH₃) bending and ring stretching displayed peaks at 1496–1368 cm⁻¹, respectively. ν(C-O-C) either vibration cited in 1318–1205 cm⁻¹. C–N stretching and aryl–O displayed bands at 1159–1024 cm⁻¹. Aromatic ν(C-H) out-of-plane ν(C-H) bending displayed peaks at 913–734 cm⁻¹. A band was observed at 2227 cm⁻¹, attributed to the ν(C≡N) stretching vibration. This band shifted lower when L₁ coordinated with the central ion due to π-back-donation into the nitrile. Which π* weakens C≡N to the red shift, as seen in

Table 1. Infrared Spectroscopic Data (ν/cm⁻¹) for N–H, ν(C≡N, C=O, C–N, C–O–C, C=C, M–N, and M–O) Modes of L₁, L₂ and Their Metal Complexes.

Sample	ν(N–H)	ν(C≡N)	ν(C=O)	ν(C–N)	ν(C–O–C)	ν(C=C) (Aryl)	ν(M–N)	ν(M–O)
L1	3339	2227	1589	1368	1105	1640	—	—
L2	2963	—	1642	1363	1100	1642	—	—
[Co(L1)Cl]Cl	2963	—	1555	1421	1106	1614	522	553
[Ni(L1)Cl]Cl	2901	—	1574	1376	1108	1552	463	556
[Mn(L1)Cl]Cl	2902	—	1505	1417	1105	1663	447	557
[Cu(L1)Cl]Cl	2995	—	1516	1409	1103	1644	494	558
[Co(L2)Cl]	3334	2196	1515	1410	1105	1643	491	554
[Ni(L2)Cl]	3333	2205	1516	1419	1104	1625	524	565
[Mn(L2)Cl]	3335	2212	1559	1406	1106	1642	526	571
[Cu(L2)Cl]	3332	2185	1509	1419	1105	1636	491	572

[15]. Finally, the peaks below 600 cm⁻¹ are attributed to the deformation of ring modes [9,16,17,18].

FTIR of complexes [M(L₁)Cl]Cl, where M can represent Mn(II), Ni(II), Cu(II) and Co(II) as central coordination ions, showed successful metal ion coordination. [M(L₁)Cl]Cl formula suggested after FTIR and HNMR, and conductivity study as explained in Section 3.1, Section 3.2 and Section 3.3. For more details, in complexes [X(L₁)Cl]Cl, slightly new bands appear in the range of (524–601) cm⁻¹, (412–464) cm⁻¹ could be attributed to M-O and M-N, respectively. The strong band of ν(C=N) or ν(C=O) stretching, which is shifted to a lower value if compared to L1, suggests coordination through nitrogen or oxygen as donor atoms. The ν(N-H) bond has been shifted down when the N atom is coordinated in complexes. Thus, the new ν(N-H) appeared at a range of (3331–3338) cm⁻¹. Finally, in all [M(L₁)Cl] complexes appeared bands (2905–2918) cm⁻¹ and (2995–3007) cm⁻¹, corresponding to ν(C-H) aromatic and aliphatic [18,19].

In a similar pattern, L₂ displayed bands as plotted in Figure 3. A broad absorption was observed at 3334 cm⁻¹ and 3284 cm⁻¹ corresponding to ν(N-H) and ν(O-H) stretching vibrations, respectively. The bands at 3010 cm⁻¹ and 2918 cm⁻¹ are attributed to aromatic and aliphatic ν(C-H) stretches. The peaks at (951, 846, and 701) cm⁻¹ are attributed to aromatic ν(C-H) vibration. The presented bands at 1515, 1466, and 1406 cm⁻¹ confirm the ν(C=C) stretches of integrity of the aromatic backbone. Strong bands appeared at (1368, 1316, 1296, 1226, 1202, 1151, 1103, 1078, and 1005) cm⁻¹, confirming ν(C–O–C) attributed to C–O–C stretching vibrations, which confirm formation of ether linkage through Williamson ether synthesis. The bands 951, 846, and 701 cm⁻¹ correspond to aromatic ν(C-H) out-of-plane bend vibrations [20].

FTIR of complexes [X(L₂)Cl], new bands appear in the range of (526–601) cm⁻¹, (404–478) cm⁻¹ correspond to M-O and M-N, respectively. ν(C=N) or ν(C=O) stretching band in complexes shifted lower wavenumber. This suggested the coordination of X central ion(II) with nitrogen or oxygen as donor atoms. It was noted also that the ν(N-H) bond has been shifted down when the N atom is coordinated in complexes. Thus, the new ν(N-H) appeared at a range of (3331–3338) cm⁻¹. Finally, in all [X(L₁)Cl]Cl complexes, bands appeared at (2905–2918) cm⁻¹ and (2995–3007) cm^−1, corresponding to ν(C-H) aromatic and aliphatic absorbance regions.

When L₁ and L₂ coordinate with Co(II), Ni(II), Cu(II), and Mn(II), they are commonly approved by new low-frequency bands of the IR spectrum. Weak to medium absorptions are often reported in the range (490–530) cm⁻¹. which is corresponding to ν(M–N) stretching. These values are consistent with ligand nitrogen atoms coordination (azomethine or nitrile donors) to the metal central ions. Additional bands observed near (555–580) cm⁻¹ are attributed to ν(M–O) stretching vibrations. It could arise from the bonding of phenolic or ether oxygen atoms to the central ions. These low-energy modes are absent in the free L₁ and L₂. They appeared only after coordination, confirming the formation of true chelate structures. The values are in high agreement with other reports for octahedral M(II) Schiff base and nitrile complexes. When ν(M–N) typically sited at (450–530) cm⁻¹ and ν(M–O) at (520–600) cm⁻¹ [21,22].

3.2. ¹H-NMR Spectra of L₁ and L₂

Figure 4 shows ¹H-NMR of L₁; as seen, the shifted peak at δ 8.05–6.78 ppm (m, ~12H) is attributed to aromatic protons that are related to naphthoxy and phenoxy moieties; (naphthyl ring can appear at δ 7.8–8.1, and phenoxy/anisole resonances can show peaks near δ 7.5 and 6.8. While allyl fragment can be observed at δ 5.9–5.1 region: δ 5.86 (m, 1H, CH=), δ 5.25 (d, J = 17 Hz, 1H, =CH₂ trans), and δ 5.12 (d, J = 10 Hz, 1H, =CH₂ cis). The diarylmethyl methine displayed peaks at δ 5.45 (d, J ≈ 6 Hz, 1H), consistent with coupling to the adjacent methylene. In addition, benzylic methylene can be sited near the allyl group to obtain peaks at δ 3.32 (s, 2H). Ether linkages observed at δ 4.25 (t, J ≈ 6.8 Hz, 2H, Ph–O–CH₂–) and δ 4.12 (t, J ≈ 6.8 Hz, 2H, Nap–O–CH₂–). A sharp singlet peak reported at δ 3.78 (s, 3H) belongs to O–CH₃. The dimethylamino arm observed as δ 2.85 (t, J ≈ 6.8 Hz, 2H, –CH₂–NMe₂) and δ 2.75 (t, J ≈ 6.8 Hz, 2H, –CH₂– between O and N), with the terminal NMe₂ methyls at δ 2.30 (s, 6H). No phenolic OH is detected (no broad signal at ~δ 4.5–5.0), consistent with etherification of the parent eugenol unit. In ¹HNMR Summary was δ 8.05–6.78 (m, ~12H, Ar–H); 5.86 (m, 1H, CH= of allyl); 5.25 (d, J = 17 Hz, 1H, =CH₂ trans); 5.12 (d, J = 10 Hz, 1H, =CH₂ cis); 5.45 (d, J ≈ 6 Hz, 1H, diarylmethyl CH); 4.25 (t, J ≈ 6.8 Hz, 2H, Ph–O–CH₂–); 4.12 (t, J ≈ 6.8 Hz, 2H, Nap–O–CH₂–); 3.78 (s, 3H, O–CH₃); 3.32 (s, 2H, benzylic CH₂ to allyl); 2.85 (t, J ≈ 6.8 Hz, 2H, –CH₂–NMe₂); 2.75 (t, J ≈ 6.8 Hz, 2H, –CH₂– between O and N); 2.30 (s, 6H, NMe₂. The absence of a broad singlet at ~4.5–5.0 ppm supports successful etherification and deprotonation of eugenol –OH [23,24].

While Figure 5 shows the ¹H NMR spectrum of L₂. The Phenolic OH peaks showed Distinct peaks, singlets s at δ 10.20 and 9.80 ppm (1H each), attributed to free two aromatic. Aromatic region at (δ 8.05–6.70 ppm with ~18–20 protons covers the naphthoxy, phenoxy, and anisole aromatic rings. However, the most deshielded protons near δ 8.0 ppm arise from peri-protons of the naphthyl fragment; other aromatic signals appear in the range of δ 7.6–6.7 ppm. Diarylmethyl CH: A showed a small doublet at δ 5.42 (J ≈ 6 Hz, 1H), belonging to the central benzylic methine linking the two aryl fragments. Ether linkages: Two nonequivalent –OCH₂– groups appear as triplets at δ 4.20 and 4.05 (J ≈ 6.8 Hz, 2H each), reflecting as two sharp singlets at δ 3.80 and 3.76 (3H each) are assigned to anisole O–CH₃ groups. The methylene was sites next to nitrogen resonates at δ 2.90 (t, J ≈ 6.8 Hz, 2H), while the terminal NMe₂ methyls appear as a singlet at δ 2.28 (6H). The δ 10.20 (s, 1H, OH); 9.80 (s, 1H, OH); 8.05–6.70 (m, ~18–20H, Ar–H); 5.42 (d, J ≈ 6 Hz, 1H, diarylmethyl CH); 4.20 (t, J ≈ 6.8 Hz, 2H, O–CH₂–); 4.05 (t, J ≈ 6.8 Hz, 2H, O–CH₂–); 3.80 (s, 3H, O–CH₃); 3.76 (s, 3H, O–CH₃); 2.90 (t, J ≈ 6.8 Hz, 2H, –CH₂–N); 2.28 (s, 6H, NMe₂). The clear presence of phenolic OH signals and sharp methoxy/dimethylamino resonances differentiates L₂ from L₁, where etherification eliminates OH peaks and modifies the side-chain environment [24,25].

3.3. Molar Conductivity, (d-d) Spectrum and Expected Geometry of the Prepared [M(L₁)Cl]Cl and [M(L₂)Cl] Complexes

Table 2. Highlighted data of Physical and analytical characterisation of L₁ and L₂, as well as their complex properties.

Compound	Colour	Yield	M.P (°C)	Conductivity (Ω−1 cm2·mol−1)	μeff (B.M)	Found (Calc.) %
						C	H	N	M
ESC	white	-	150	-	-	73.98	6.47	8.63	-
CUR	yellow	-	183	-	-	68.4	5.42	-	-
EUG	colourless	-	liquid	-	-	73.17	7.31	-	-
L1	yellow	71%	218	-	-	74.4 (73.9)	6.21 (6.6)	6.67 (6.35)	-
L2	Off-white	73%	223	-	-	74.6 (77.9)	6.65 (6.9)	6.16 (5.8)	-
[Co(L1)Cl]Cl	green	82%	240 °C	25	5.10	67.84 (66.9)	5.84 (5.78)	5.45 (5.5)	11.48 (11.5)
[Ni(L1)Cl]Cl	green	81%	280 °C	29	3.31	67.87 (66.98)	5.85 (5.80)	5.46 (5.49)	11.44 11.00)
[Mn(L1)Cl]Cl	brown	88%	268 °C	32	3.98	(68.36) (67.90)	5.89 (5.77)	5.50 (5.48)	10.80 (10.35)
[Cu(L1)Cl]Cl	Brown	75%	257 °C	28	2.80	67.24 (66.89)	5.79 (5.93)	5.41 (5.22)	12.27 (12.98)
[Co(L2)Cl]	Blue	68%	184 °C	8	5.10	65.60 (64.93)	5.33 (5.29)	3.73 (2.89)	7.85 (7.88)
[Ni(L2)Cl]	green	75%	209 °C	7	3.38	65.62 (66.09)	5.33 (5.41)	3.73 (2.91)	7.82 (7.66)
[Mn(L2)Cl]	Brown	84%	186 °C	11	3.98	65.95 (65.44)	5.36 (5.78)	3.75 (2.89)	7.37 (6.89)
[Cu(L2)Cl]	green	79%	192 °C	10	2.80	65.20 (64.87)	5.30 (5.26)	3.71 (3.65)	8.41 (8.36)

Measurement that carried out at (1 × 10⁻³) M in Dimethyl sulfoxide (DMSO) solvent, colour, melting point (M.P), effective magnetic moment in Bohr magnetons (B.M) and found (calculated CHN and/or M) quantitative analysis values of [M(L₁)Cl]Cl and of [M(L₂)Cl] complexes.

displayed some highlighted physical properties such as molar conductivity of their complexes measurement that carried out at (1 × 10⁻³) M in Dimethyl sulfoxide (DMSO) solvent, colour, melting point (M.P), effective magnetic moment in Bohr magnetons (B.M) and found (calculated CHN and/or M) quantitative analysis values of [M(L₁)Cl]Cl and of [M(L₂)Cl] complexes. As seen, all L₁-coordination complexes exhibit conductivity in the range of (22–32) Ω⁻¹ cm²·mol⁻¹, revealing 1:1 electrolytic behaviour. This indicates the prepared complexes are partially dissociating in DMSO solvent to result in mono-cationic complex species and free anion. At the same time, L₂ complexes showed non-conductive activity.

As seen, all L₁-coordination complexes exhibit conductivity in the range of (22–32) Ω⁻¹ cm²·mol⁻¹, revealing 1:1 electrolytic behaviour. This indicates the prepared complexes are partially dissociating in DMSO solvent to result in mono-cationic complex species and free anion, while L₂ complexes showed non-conductive activity.

The magnetic moment of both Ni(II) complexes [Ni(L₁)Cl] and [Ni(L₂)Cl] reported (3.31–3.38) (B.M) indicated an octahedral geometry (high spin) with electron configuration of 3d⁸. This electron configuration can be split into t₂g⁶eg² with 2 unpaired electrons. Thus, the expected (d-d) spectra of Ni(II) d⁸ high spin can show three allowed spins from the (³A₂g) as the ground state term. The allowed-spin are (³A₂g → ³T₂g) cm⁻¹, (³A₂g → ³T₁g_(F)) and ³A₂g → ³T₁g_(P). They often cited at region (~9000–10,500), (~14,300–15,400) and (~20,000–22,500) cm⁻¹, respectively. Consistently, in practical experiment d-d spectra of Ni(II) d⁸ high-spin showed three main regions at (9225–9615), (14,477–15,025) and (21,045–22,300) cm⁻¹

In a similar pattern, [Co(L₁)Cl]Cl and [Co(L₂)Cl] complexes exhibit a magnetic moment of (4.61–5.10) (B.M). They also indicated an octahedral geometry (high spin) with an electron configuration of 3d⁷. Their electron configuration can be split to t₂g⁵eg² with 3 unpaired electrons. (d-d) spectra of Co(II) d⁷ high spin has three allowed-spin ⁴T₁g_(F) → ⁴T₂g_(F), ⁴T₁g_(F) → ⁴A₂g_(F) and ⁴T₁g_(F) → ⁴T₁g_(P) at regions (~8000–9000), (~16,000–18,000) and (~19,000–22,000) cm⁻¹, respectively. Practically, regions of allowed the spin of Co(II) d⁷ recorded at (8220–9924), 16,220–17,564) and (19,893–21,636,363) cm⁻¹.

[Mn(L₁)Cl] and [Mn(L₂)Cl] complexes showed a magnetic moment (5.91–5.94) B.M. They expected to have d⁵ splitting to t₂g³eg² with 5 unpaired electrons. While the (d-d) spectrum of prepared Mn(II) complexes assigned weak (d–d) absorbed bands at (20,800–24,200) and (15,380–17,210) cm⁻¹. These bands attributed to ⁶A₁g → ⁴T₁g_(G) and ⁶A₁g → ⁴T₂g_(G). These results are consistent with previous spectral data reported for octahedral (high-spin) Mn(II) complexes. The weak d-d absorption corresponded to the forbidden-spin nature of these transition bands, due to vibronic coupling and spin–orbit interaction. That confirms the octahedral high-spin configuration of Mn(II).

Finally, (d-d) transition spectrum of [Cu(L₁)Cl]Cl and [Cu(L₂)Cl] d⁹ (t₂g⁶eg³) showed weak and broad bands in the range (12,600–16,870) cm⁻¹. In spite of its d-d transition allowed-spin ²Eg→²T₁g, the band was weak and broad. This is attributed to LaPorte’s centrosymmetric field of [Cu(L)Cl]. As well as the electrons-vibronic coupling.

From all previous investigations, the suggested scheme formula structure of complexes of [ML₁)Cl]Cl and [ML₂)Cl] are shown in Figure 6a and Figure 6b, respectively.

The successful synthesis of [M(L₁)Cl] and b [M(L₂)Cl] complexes was confirmed through FTIR and ¹H NMR spectroscopy. FTIR spectra of metal–ligand bands were confirmed in the range of 420–550 cm⁻¹. ν(N-H) and ν(C=O) stretches were shifted down due to the coordination bond forming of (M--N) and (M--O), respectively. At the same time, ¹H NMR showed ether formation as well as aromatic and aliphatic protons in the 6.8–7.1 ppm range. This is a complex method procedure. It is opening pathways for developing metal-based therapeutic candidates with dual bioactivity.

3.4. Antimicrobial Activities of [M(L₁)Cl] and [M(L₂)Cl] Complexes

The antimicrobial activities of prepared complexes [M(L₁)Cl], [M(L₂)Cl] and free ligand were investigated vs. Escherichia coli (St = 24), Staphylococcus aureus, and Candida albicans (St = 21) using agar well diffusion method at a range concentrations of (100, 50, 25, and 12.5) mg/mL. The results can be seen in

Table 3. Antimicrobial activities of prepared metal complexes against Candida albicans, Staphylococcus aureus, and Escherichia coli in different concentrations expressed as inhalation zone area (St.mm).

Complexes	Conc. mg/mL	Escherichia coli St = 24	Staphylococcus aureus St = 25	Candida albicans St = 21
[Cu(L1)Cl]	100	16.5	23	13
	50	12.5	18.5	9
	25	R	14.5	R
	12.5	R	R	R
[Cu(L2)Cl]	100	17.5	24	14
	50	13.5	19.5	10
	25	R	15.5	R
	12.5	R	R	R
[Ni(L1)Cl]	100	11.5	15	15
	50	R	12.5	R
	25	R	R	R
	12.5	R	R	R
[Ni(L2)Cl]	100	12.5	16	16
	50	R	13.5	R
	25	R	R	R
	12.5	R	R	R
[Mn(L1)Cl]	100	R	R	R
	50	R	R	R
	25	R	R	R
	12.5	R	R	R
[Mn(L2)Cl]	100	R	R	R
	50	R	R	R
	25	R	R	R
	12.5	R	R	R
[Co(L1)Cl]	100	17.5	32.5	26.1
	50	13	28.2	21
	25	10.5	21	13
	12.5	R	17	R
[Co(L2)Cl]	100	19.5	31.5	25
	50	14	27.2	20
	25	11	20	12
	12.5	R	16	R
L1	100	R	R	12.5
	50	R	R	10.5
	25	R	R	R
	12.5	R	R	R
L2	100	R	R	11.5
	50	R	R	11
	25	R	R	R
	12.5	R	R	R

.

Copper complexes [Cu(L₁or₂)Cl] at 100 mg/mL exhibited a moderate activity against E. coli, with inhibition zones of 17.5 mm, higher activity against S. aureus in 23 mm against and lower activity against C. albicans. However, the activity decreased with a decrease in complex concentration. [Ni(L₁or₂)Cl] and [Mg(L₁or₂)Cl] exhibit negligible to non-activity behaviour against the tested microorganisms.

Copper complexes [Cu(L₁or₂)Cl] at 100 mg/mL exhibited a moderate activity against E. coli, with inhibition zones of 17.5 mm, higher activity against S. aureus in 23 mm against and lower activity against C. albicans. However, the activity decreased with a decrease in complex concentration. [Ni(L₁or₂)Cl] and [Mg(L₁or₂)Cl] exhibit negligible to non-activity behaviour against the tested microorganisms.

In contrast, Cobalt complexes [Co(L₁)Cl] demonstrated broad-spectrum activity at 100 mg/mL, reaching up to (32.5–31.5) mm vs. S. aureus, (26.1–25) mm vs. C. albicans and (17.5–18.5) mm vs. E. coli, showing superior antimicrobial behaviour among other complexes. In a similar pattern of Cu-complexes, the activity became less at lower Co-complex conc. Finally, the ligands L₁ and L₂ exhibit weak to acceptable inhibition at higher concentrations.

Overall, Co(II) complexes demonstrated the highest antimicrobial activity, potentially due to an increase in lipophilicity and an improvement of diffusion via microbial cell membranes upon Co-coordination, as shown in Figure 7.

3.5. Density Functional Theory (DFT)

At times, the lack of a crystal structure necessitated computer investigations to gain a better understanding of the molecular structures of the complexes. The GW9 Gaussian 16 program was utilised to conduct geometric optimisations. The structures of the investigated compounds were optimised at the B3LYP/6-311G(d,p) level, as applied in the Gaussian 09W software (version number A.02) [26]. The GaussView 6 package was used to draw the primary structures and visually display the results. The computational optimisation was performed in the gas phase at the ground state. DFT calculations were employed to determine the 3D optimised structures of the compounds, as shown in Figure 9, as well as to analyse the HOMO-LUMO diagram, as shown in Figure 10 and Figure 11. These describe the ultimate electron transfer interactions within the chemical compound, including electronegativity (χ), chemical potential (μ), global hardness (η), global softness (S), and the global electrophilicity index (ω) [27,28], which are listed in

Table 4. The calculated energy values of ligands and their Mn(II) and Co(II) complexes using the DFT/B3LYP method.

Compound	EHOMO (eV)	ELUMO (eV)	ΔE (eV)	µ (Debye)	χ (eV)	η (eV)	σ (eV)	ω (eV)	ΔNmax
L1	−5.429	−1.285	4.144	−3.357	−3.357	2.072	0.241	2.719	2.551
Mn(II)-complex	−5.533	−1.360	4.173	−3.446	− 3.446	2.086	0.240	2.847	1.652
Co(II)-complex	−6.130	−2.350	3.780	−4.780	−4.240	1.880	0.520	4.763	2.246
L2	−5.641	−1.473	4.168	−3.557	−3.557	2.084	0.240	3.036	1.620
Mn(II)-complex	−5.627	−1.460	4.167	−3.544	−3.544	2.082	0.240	3.013	1.652
Co(II)-complex	−5.831	−2.547	3.284	−4.189	−4.189	1.642	0.305	5.343	1.701

I = −E_HOMO; A = −E_LOMO; (ΔE) = E_LUMO − E_HOMO; μ = −(I + A)/2; χ = (I + A/2); η = (I − A)/2; Pi = −χ; σ = 1/η; S = 1/2η; ω = Pi2/2η; ∆N max = Pi/η.

.

DFT Calculations

The synthesised complexes were optimised using the density functional theory (DFT) method with the 6–31G (d, p) basis set at the B3LYP level in a DMSO medium. The HOMO and LUMO, along with their energy gap, of some synthesised complexes are illustrated in Figure 8 and listed in Table 3. The B3LYP/6-311G(d,p) module type was used to theoretically create the geometric structures of compounds as seen in Figure 9. Chemical descriptors such as hardness and softness, derived from these energies, provide insight into reactivity. Figure 9 and Figure 10 display the molecular orbital structure of ligands and their Mn(II) and Co(II) complexes, illustrating the significance of the HOMO and LUMO in electron donation and acceptance. The energy gap between these orbitals influences the molecule’s stability and reactivity, with smaller gaps indicating higher polarizability and larger gaps indicating greater stability but lower reactivity. Parameters like electrophilicity (ω) and hardness (η) further evaluate stability and reactivity [29]. The high electrophilicity value of Co(II) complexes suggests strong biological activity. Molecular stability and reactivity can be inferred from the calculations of both absolute softness (σ) and absolute hardness (η) parameters. Additional parameters such as global electrophilicity (ω), global softness (S), electrophilicity index (χ), and chemical potential (μ) have been calculated using HOMO and LUMO energies [30]. The high electrophilicity value of Co(II) complexes suggests strong biological activity. Molecular stability and reactivity can be inferred from the calculations of both absolute softness (σ) and absolute hardness (η) parameters. Additional parameters such as global electrophilicity (ω), global softness (S), electrophilicity index (χ), and chemical potential (μ) have been calculated using HOMO and LUMO energies [31], as previously shown in Table 3. At the same time, the electronic charge (∆N max) was calculated for molecules (Table 4). The high ω value of two Co(II) complexes indicates a strong potential for biological activity, which is further confirmed by the experimental data.

The minimum electrophilicity theory can be used to estimate the reactivity of the ligand and metal complexes. According to the theory of minimum electrophilicity (ω), compounds with the lowest electrophilicity exhibit the highest stability [31,32], as previously shown in Table 4.

Figure 8. HOMO and LUMO orbitals of the synthesised ligands.

Figure 8. HOMO and LUMO orbitals of the synthesised ligands.

Figure 9. Optimized geometry of some synthesized L₁ and L₂-Coordination compounds.

Figure 9. Optimized geometry of some synthesized L₁ and L₂-Coordination compounds.

Figure 10. HOMO and LUMO orbitals of some synthesised complexes Mn(II) and Co(II) through L₁.

Figure 10. HOMO and LUMO orbitals of some synthesised complexes Mn(II) and Co(II) through L₁.

Figure 11. HOMO and LUMO orbitals of some synthesised complexes Mn(II) and Co(II) through L₂.

Figure 11. HOMO and LUMO orbitals of some synthesised complexes Mn(II) and Co(II) through L₂.

4. Conclusions

Biological mixed ligands based on escitalopram–eugenol and escitalopram–curcumin were prepared, coordinated with transition metal ions and characterised successfully. The coordination Mn(II), Cu(II), Zn(II), Fe(II), and Co(II) complexes showed predominantly octahedral geometries. The stable coordination occurs through oxygen and nitrogen as donor sites. The magnetic measurement exhibits high-spin states for Mn(II), Co(II), and Ni(II) complexes. This is consistent with their electronic configurations, while Cu(II) complexes showed distorted octahedral geometry with broad d–d bands. Biological investigation demonstrated that cobalt(II) complexes have promising antimicrobial activity, which enhances their potential as therapeutic agents. DFT reported results provide additional structural information with minimised energy confirmation. It is also revealed to be a strong foundation for future investigations into the pharmacological applications. Further investigations are recommended, including in vivo practical experiments and comprehensive biological scanning, to confirm their therapeutic potential or their clinical applicability.