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New Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Zn(II), Cd(II), and Hg(II) Gibberellate Complexes: Synthesis, Structure, and Inhibitory Activity Against COVID-19 Protease


Transition metals such as Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Zn(II), Cd(II), and Hg(II) have been reacted with gibberellic acid (HGA) to give novel complexes, and those have been characterized by physical, spectral and analytical methods. The plant hormone gibberellate acts as a deprotonated bidentate ligand in the complexation reaction with central metal ions in the ratio 1 : 2 (Mn+ : GA). The complexes [M(GA)2(H2O)2], where [M = Mn(II), Co(II), and Ni(II)] form octahedral structures, while [M(GA)2] complexes [M = Zn(II), Cd(II), and Hg(II)] display four-coordination geometry. The octahedral structures of Cr(III) and Fe(III) complexes are characterized by the general formula [M(GA)2(H2O)(Cl)]. Computational study carried out has determined possible interactions of the complexes with COVID-19 (6LU7).


Gibberellic acid (HGA) is a tetra-terpenoid compound [1] that acts as a plant hormone stimulating plants growth and development. Understanding the appropriate mechanism of HGA transport and action upon plant growth, flower development, sexual expression, grain development, and seeds germination is the objective of extensive research [2, 3].

So far there are no publications on metals chelation with gibberellic acid, except our published paper devoted to the structural, morphological and biological properties of (NH4)2[PtL(H2O)2]Cl3·2H2O, [AuLCl2]·3H2O, [RuL(NH3)2Cl2]·6H2O, [VL(NH3)2Cl2]·2H2O, and [SeOL(H2O)Cl]·3H2O (where L: GA) complexes with the ions of Pt(II), Au(III), Ru(III), V(III), and Se(IV) [4]. In continuation of that research, we report here new transition metals Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Zn(II), Cd(II), and Hg(II) complexes with gibberellic acid. Influence of different ions nature upon chelation is discussed. Interactions of the complexes with COVID-19 protease (6LU7) by means of molecular docking are considered.


Gibberellic acid and metal chlorides were received from Sigma–Aldrich Chemical Corporation, St. Louis, Mo, USA. Those were of analytical grade and used without further purification.

Melting points of all synthesized complexes were measured on a MPS10-120 melting point apparatus. Molar conductance of the complexes was measured in DMSO (l.0×10–3 mol/dm3) solutions at 30°C on a Jenway 4010 conductivity meter. Magnetic susceptibility measurements were performed on a SHERWOOD SCIENTIFIC magnetic susceptibility balance. IR spectra (KBr discs) were recorded on a Bruker FTIR spectrophotometer. UV-Vis spectra were recorded on a UV2 Unicam UV/Vis spectrophotometer. 1H NMR spectra were measured on a Bruker DRX-250 spectrometer (600 MHz) using DMSO-d6 as a solvent. ESR spectra were measured on a JES-FE2XG EPR spectrometer. Elemental analysis of the complexes was carried out on a PerkinElmer 2400 organic elemental analyzer. Percentage of the metal ions was determined by the gravimetric method.

The complexes of Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Zn(II), Cd(II), and Hg(II) with gibberellic acid were prepared by the general procedure. The desired anhydrous metal chloride salt (1 mmol) was dissolved in 20 mL of distilled water, and the solution was slowly added to 20 mL of 2 mmol methanol (95%) solution of gibberellic acid upon magnetic stirring. The pH of the reaction mixture was maintained ca 7–8 by adding 10% alcoholic ammonia solution, and the mixture was refluxed for ca 2 h. The precipitate was filtered off while hot and washed with hot methanol, diethyl ether and dried over anhydrous CaCl2 in a vacuum desiccator to give the corresponding solid complex.

[Cr(GA)2(H2O)(Cl)]. Dark blue, yield 66%, mp 245°C, Λm = 12 Ω1 cm2 mol1. IR spectrum, ν, cm–1: 1604 νas(COO), 1331 νs(COO). Found, %: С 57.21; Н 5.49; M 6.46. C38H44ClCrO13. Calculated, %: С 57.32; Н 5.57; Cr 6.53. M 796.20.

[Fe(GA)2(H2O)(Cl)]. Reddish brown, yield 69%, mp 272°C, Λm = 17 Ω1 cm2 mol1. IR spectrum, ν, cm–1: 1590 νas(COO), 1330 νs(COO). Found, %: С 57.01; Н 5.50; M 6.93. C38H44ClFeO13. Calculated, %: С 57.05; Н 5.54; Fe 6.98. M 800.05.

[Mn(GA)2(H2O)2]. Light brown, yield 71%, mp 264°C, Λm = 10 Ω1 cm2 mol1. IR spectrum, ν, cm–1: 1565 νas(COO), 1331 νs(COO). Found, %: С 58.32; Н 5.88; M 6.97. C38H46MnO14. Calculated, %: С 58.39; Н 5.93; Mn 7.03. M 781.71.

[Co(GA)2(H2O)2]. Red, yield 68%, mp 257°C, Λm = 11 Ω1 cm2 mol1. IR spectrum, ν, cm–1: 1612 νas(COO), 1379 νs(COO). Found, %: С 58.04; Н 5.87; M 7.44. C38H46CoO14. Calculated, %: С 58.09; Н 5.90; Co 7.50. M 785.71.

[Ni(GA)2(H2O)2]. Green, yield 74%, mp 266°C, Λm = 14 Ω1 cm2 mol1. IR spectrum, ν, cm–1: 1612 νas(COO), 1332 νs(COO). Found, %: С 58.07; Н 5.85; M 7.40. C38H46NiO14. Calculated, %: С 58.11; Н 5.90; Ni 7.47. M 785.47.

[Zn(GA)2]. White, yield 64%, mp 283°C, Λm = 9 Ω1 cm2 mol1. IR spectrum, ν, cm–1: 1621 νas(COO), 1333 νs(COO). Found, %: С 60.21; Н 5.56; M 8.46. C38H42O12Zn. Calculated, %: С 60.36; Н 5.60; Zn 8.65. M 756.12.

[Cd(GA)2]. White, yield 66%, mp 289°C, Λm = 13 Ω1 cm2 mol1. IR spectrum, ν, cm–1: 1561 νas(COO), 1330 νs(COO). Found, %: С 56.77; Н 5.20; M 13.78. C38H42CdO12. Calculated, %: С 56.83; Н 5.27; Cd 14.00. M 803.16.

[Hg(GA)2]. White, yield 65%, mp 222°C, Λm = 11 Ω1 cm2 mol1. IR spectrum, ν, cm –1: 1556 νas(COO), 1329 νs(COO). Found, %: С 51.19; Н 4.72; M 22.43. C38H42HgO12. Calculated, %: С 51.21; Н 4.75; Hg 22.50. M 891.33.


The synthesized Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Zn(II), Cd(II), and Hg(II) complexes were insoluble in common organic solvents such as methanol, ethanol, chloroform, or benzene, but soluble in DMSO and DMF. Molar conductance values of the complexes in DMSO were low (9–17 Ω–1 cm2 mol–1) indicating those as non-electrolytes [5]. The physical and analytical data accumulated for the complexes were in good agreement with the proposed molecular formulae viz. [M(GA)2(H2O)2] [where M = Mn(II), Co(II), and Ni(II)], [M(GA)2] [where M = Zn(II), Cd(II), and Hg(II)] and [M(GA)2(H2O)(Cl)] [where M = Cr(III) and Fe(III)].

IR spectra of free gibberellic acid and its complexes are listed in Table 1. In case of the complexes, the stretching vibrations ν(O–H) bands were recorded in the range of 3330–3396 cm–1 due to deprotonation of the carboxylic group and its involvement in complexation with the central metal ions. The characteristic band of ν(C=O) at 1750 cm–1 of the free ligand was recorded at the same frequency as in IR spectra of the complexes. The band at 1660 cm–1 assigned to the ν(C=O) of free HGA was absent in the spectra of the synthesized complexes. There were recorded two new vibration bands in the ranges of 1621–1556 and 1379–1329 cm–1 assigned to νas(C=O) and νa(C=O) of the carboxylate group. The calculated values of [Δν(COO)] (Table 2) that were in the range of 288– 227 cm–1 confirmed the bidentate coordination modes [57]. The new vibration bands in the range of 644– 537 cm–1 were assigned to ν(M–O) [6].

Table 1. IR spectral data (cm–1) for gibberellic acid and its complexes
Table 2. IR spectral data for the carboxylate group of the complexes

UV-Vis spectra bands recorded for HGA in the range of 200–300 nm were assigned to π–π* transitions. The broad band observed in the visible region of the complexes spectra was attributed to dd transitions of the metal ions.

Electronic spectrum of Cr(III) complex exhibited the spin transitions at 393, 451 and 566 nm due to 4A2g4T1g (P) (ν3), 4A2g4T1g (F) (ν2), and 4A2g4T2g (F) (ν1), respectively, and indicated an octahedral geometry of the complex, which was supported by ν2 to ν1 ratio of 1.25 [7]. At room temperature magnetic moment of the complex was measured to be 3.61 B.M., close to the spin only value suggesting an octahedral geometry around chromium ion [8].

The spectrum of Mn(II) demonstrated the bands at 806 and 823 nm of the electronic transfers 6A1g4T2g(G) and 6A1g4T1g(G), respectively, and proposed the octahedral structure of Mn(II) ion [7]. The effective magnetic moment value of the complex was 5.92 B.M.

The spectrum of Fe(III) complex demonstrated the bands at 652 nm (ν1), 470 nm (ν2) and 447 nm (ν3) assigned to the transitions 6A1g4T1g (D), 6A1g4T1g and 6A1g4T2g, respectively. The magnetic moment value of 5.55 B.M. confirmed the high spin octahedral geometry of the complex [7].

The spectrum of Co(II) complex contained four bands at 308, 381, 680, and 820 nm attributed to C–T mixed with 4T1g(F) → 4T1g(P), 4T1g(F) → 4A2g and 4T1g(F) → 4T2g(F) respectively assigned to octahedral Co(II) ion [912], which was confirmed by the effective magnetic moment value of 4.75 B.M. assigned to three unpaired electrons per Co(II) ion.

The spectrum of Ni(II) complex exhibited three electronic transition bands at 811, 611 and 386 nm assigned to 3A2g3T2g(F) (ν1), 3A2g(F) → 3T1g(F) (ν2) and 3A2g(F) → 3T2g(P) (ν3) transitions, respectively, attributed to octahedral geometry [7]. The μeff value of 3.20 B.M. corresponded to two unpaired electrons per Ni(II) ion with the ideal six-coordinated configuration. The ratio of ν21 (1.32) supported the octahedral structure of the complex [7, 8].

The Zn(II), Cd(II), and Hg(II) complexes were determined to be diamagnetic demonstrating no d-d bands and their spectra demonstrated only charge transfer bands.

1H NMR spectra. Gibberellic acid. 1H NMR spectrum, δ, ppm: 1.07 s (3H, CH3), 1.66 d (1H, J = 6.6 Hz, C11H), 1.71–1.74 m (3H, C4bH, C5H, C6H), 1.84 d (1H, J = 6.6 Hz, C11H), 1.86 m (1H, C6H), 1.91 m (1H, C5H), 2.11 d (1H, J = 16.2 Hz, C9H), 2.17 d (1H, J = 16.2 Hz, C9H), 2.48 d (1H, J = 10.6 Hz, C10aH), 3.02 d (1H, J = 10.2 Hz, C10H), 3.55 d (1H, J = 3.16 Hz, C2H), 3.87 s (1H, C7OH), 4.85 s (1H, C2OH), 5.10 d (1H, J = 8.16 Hz, CmethyleneH), 5.56 d (1H, J = 8.12 Hz, CmethyleneH), 5.78 m (1H, C3H), 6.32 d (1H, J = 9.36 Hz, C4H), 12.55 sb (1H, COOH).

Cd(II) complex. 1H NMR spectrum, δ, ppm: 1.02 s (3H, CH3), 1.57 d (1H, J = 6.6 Hz, C11H), 1.61–1.63 m (3H, C4bH, C5H, C6H), 1.76 d (1H, J = 6.6 Hz, C11H), 1.83 m (1H, C6H), 2.03 m (1H, C5H), 2.11 d (1H, J = 11.96 Hz, C9H), 2.38 d (1H, J = 6.8 Hz, C9H), 2.46 d (1H, J = 10.68 Hz, C10aH), 3.01 d (1H, J = 10.6 Hz, C10H), 3.12 d (1H, J = 13.64 Hz, C2H), 4.78 m (1H, C3H), 5.03 s (1H, C7OH), 5.61 s (1H, C2OH), 5.71 d (1H, J = 3.56 Hz, CmethyleneH), 5.73 d (1H, J = 3.60Hz, CmethyleneH), 6.26 d (1H, J = 9.36 Hz, C4H).

The combination of microanalytical and spectroscopic characteristics of the gibberellic acid (Fig. 1) and its complexes (Fig. 2) indicated that the deprotonated acid acted as a bidentate chelate towards the studied metal ions giving the complexes [M(GA)2(H2O)2] (where M = Mn(II), Co(II), and Ni(II)], [M(GA)2] [where M = Zn(II), Cd(II), and Hg(II)], and [M(GA)2(H2O)(Cl)] [where M = Cr(III) and Fe(III)] (Fig. 2).

Fig. 1.
figure 1

Molecular structure of gibberellic acid (HGA).

Fig. 2.
figure 2

Proposed structures of gibberellic acid complexes with metals.

Molecular docking. In this study Auto Dock (ADT) programming was used for the docking procedure. Optimization of the ligand was performed prior to docking by Avogadro version 1.2. The structure of COVID-19 protease (6LU7) was downloaded from the Protein Data Bank ( ) [10]. In the AutoDock Tools, the 6LU7 was prepared for docking by adding polar hydrogen bonds and Kollman & Gasteiger charges. We characterized the grid size for the receptor, and Lamarckian Genetic Algorithm was appointed to do the molecular docking as portrayed in this study. The output obtained was further analyzed and visualized utilizing the discovery studio program.

It was apparent that the complexes under study might have one-of-a-kind effects on COVID-19 protease. The active sites of 6LU7 were revealed from the PDB files using discovery studio (Table 3). The helical models of the compounds with 6LU7 are presented in Fig. 3, and the most conceivable docking present among 6LU7 and various compounds and interactions with different amino acids are represented in Fig. 4. The highest binding energy was determined for Mn(II) gibberellate complex (Table 3), which might act as a potential inhibitor of 6LU7.

Fig. 3.
figure 3

Helical models of giberelette complexes with (a) Co(II); (b) Cr(III); (c) Cd(II); (d) Mn(II); (e) Hg(II); (f) Fe(III); (g) Zn(II), and (h) Ni(II).

Fig. 4.
figure 4

Molecular docking poses of the gibberellate complexes with COVID-19 protease (6LU7) representing interactions with amino acids: (a) Co(II); (b) Cr(III); (c) Cd(II); (d) Mn(II); (e) Hg(II); (f) Fe(III); (g) Zn(II), and (h) Ni(II).

Table 3. Docking parameters


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Taif University Researches Supporting Project number (TURSP-2020/01), Taif University, Taif, Saudi Arabia.

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Correspondence to Moamen S. Refat.

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Refat, M.S., Altalhi, T., Bakare, S.B. et al. New Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Zn(II), Cd(II), and Hg(II) Gibberellate Complexes: Synthesis, Structure, and Inhibitory Activity Against COVID-19 Protease. Russ J Gen Chem 91, 890–896 (2021).

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  • gibberellic acid; chelation; transition metals
  • COVID-19