Phenyl Conjugation Effect on Fe 3+/2+ Formal Potential of FeN 4 -macryclic Complex

doi:10.21203/rs.3.rs-2148188/v1

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Phenyl Conjugation Effect on Fe 3+/2+ Formal Potential of FeN 4 -macryclic Complex

https://doi.org/10.21203/rs.3.rs-2148188/v1

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published 13 Jun, 2023

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The monitoring of shifting of the redox potential of macrocyclic complexes towards anodic or cathodic regions, which acts as a mediator in many electrocatalytic events, is made possible by inserting electron donating or withholding groups into their frameworks. Herein, using a template strategy, two [14]-membered N₄-macrocyclic complexes (denoted as complex A and complex B) with similar molecular cores but different phenyl moieties were prepared and characterized using multiple characterization techniques. The characterization results suggested a saddle-shaped geometry for these complexes, which might be due to the steric repulsions between the benzenoid and amidic moieties on the macrocyclic framework, as also supported by theoretical computations. Further, to investigate the electrochemical behaviors of these complexes, cyclic voltammetry was used and found that the Fe^3+/2+ redox potential was systematically shifted in anodic direction with the increment of phenyl moieties on the [14]-membered N₄-macrocyclic core. DFT calculations indicated the down-shifting in the most occupied molecular orbital due to the increased phenyl conjugation, which could be correlated with the shifting of Fe^3+/2+ redox potential. Biological evaluation of these complexes has also been carried out.

FeN4-macrocyclic complexes

spectral characterization

cyclic voltammetric studies

antibacterial activity

The functions of macrocyclic complexes cover biological, therapeutic, [1] electrochemical [2], electrocatalytic, and energy-related applications [3]. However, it is difficult to design and fabricate a suitable molecular model for a specific application. Macrocyclic chemistry provides fascinating strategies [4] to formulate a chemical design involving metals and ligands in the form of macrocyclic complexes for chemical, biological, therapeutic, and electrochemical applications [5, 6]. Due to their structural diversity and potential applications in electrochemistry, macrocyclic complexes have attracted a great deal of attention following chemical modifications [7]. This includes substitution in the molecular framework and the replacement of core metal ions. In addition, these complexes possess distinct highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels. The chemical modification of the complexes offers well-tuned HOMO and LUMO energy levels, which can be correlated to their stability and reversibility during electrochemical processes [8].

Besides, several electrocatalytic processes rely on the macrocyclic complexes' M(III)/M(II) redox potential (M = Mn, Fe, and Co). The HOMO and LUMO energy levels of macrocyclic complexes are believed to be largely dependent on the MN_x-environment, which determines the metal ion's redox potential. For instance, either electron-donating groups or electron-withdrawing groups can change the M(III)/M(II) redox potential [9, 10]. Typically, a negative M(III)/M(II) redox potential makes the metal center easier to get oxidized, whereas an increasing positive formal potential makes the metal center getting oxidized more difficult. Moreover, the M(III)/M(II) redox couple potential was believed to represent the eg-orbital energy [11]. Therefore, a deep understanding of the mode of interaction between the ligand and metal ion is essential to compute quantum parameters in order to determine the nature of the ligand, stability, and reactivity of these complexes. As for living systems, the importance of metal ions rests on their confinement inside roughly planar tetra-dentate and enclosed macrocyclic frameworks with substantial conjugation [12].

In this work, two [14]-membered N₄-macrocyclic complexes with similar molecular cores but a difference in the number of phenyl moieties (denoted as complex A and complex B), are prepared using a template method. The characterization and theoretical results agreed with their saddle-shaped geometry. Cyclic voltammetric studies suggested that the Fe(III)/Fe(II) redox potential was systematically shifted in anodic direction with the increase in phenyl moieties on [14]-membered N₄-macrocyclic core as also supported by theoretical calculations.

2.1. Materials and methods

3,4-diaminobenzene (DAB), 2,3-diamino-naphthalene (DAN), acetyl acetone (AA), hexa-hydrated iron (II) chloride, and tetraethyl-ammonium perchlorate (TEAP) were procured from TCI India. The solvents including, ethyl alcohol, methyl alcohol, diethyl ether, acetone, dimethyl sulfoxide used were of AR grade. The microanalysis (C, H, N) and mass spectral studies of these compounds were carried out at CIL Panjab University Chandigarh (Eager Xperience and TOF MS ES + 6018e3). Infrared spectra were recorded using KBr DRS system (Shimadzu 8400S). The electronic spectra were recorded on Double Beam Spectrophotometer (Perkin Elmer 2550) in ethanol. The conductivity measurements were carried out in DMSO solution using an Auto-ranging Conductivity/TDS Meter (TCM 15+). The magnetic moment of the complexes was determined at room temperature using a magnetic susceptibility balance (JMC System Division).

2.1. Preparation of the macrocyclic complexes A and B

The macrocyclic complexes A and B have been synthesized following a reported strategy [13, 14]. To prepare complex A, typically, 2 moles of DAB (0.244 g), 2 moles of AA (0.420 g) and 1 mole of hexa-hydrated iron (II) chloride (0.234 g) were mixed in 60 mL ethanol in a round bottom flask, followed by refluxing at 70°C for 12 hr. The dark brown slurry produced was concentrated in a rotatory evaporator. The crude material thus obtained was washed several times with methanol, diethyl ether, acetone, and finally with methanol, and re-crystalized in ethyl alcohol. Finally, the crystals were dried over night at 60°C in a hot-air oven. The similar strategy was adopted except that 2 moles of DAN (0.158 g) were taken in place of 2 moles of 3,4-diaminotoluene (0.244 g) for synthesis of complex B. The characterization data of these complexes is provided in Table 1.

3.1. Synthesis and Characterization

These complexes were prepared by reflux-reaction using 2 mole of diamine, 2 mole of ketone and 1 mole of metal salt at 70°C. In this reaction, metal ion plays key role to direct the reactant components to make macrocyclic framework directly. A systematic synthesis scheme for both the complexes A and B is shown in Fig. 1. Further these synthesized complexes were characterized systematically using various analytical techniques.

For characterization of functionalities in the prepared macrocyclic complexes, FTIR spectral analysis were carried out. The FTIR spectra of these complexes (Fig. 2a) showed a strong band in the range of 1645–1650 cm^− 1, which can be assigned due to C = N stretching frequency (v_(C=N)).

Whereas, other characteristic bands in the region 2830–2860 cm^− 1, 1030–1130 cm^− 1, and 750–755 cm^− 1 may be allocated to C-H bond stretching of CH₃ group and vibrations of aromatic C-H, respectively [15, 16]. In addition, a band also appeared in the region 610–620 cm^− 1 corresponding to ν(Fe-N) vibrations for these complexes.

Further, the magnetic moments of both the complexes A and B was found to be 5.87 B.M. at ambient temperature. This value corresponds to high spin configuration for Fe(II) metal ion, demonstrating the presence of an D_4h-symmetry around Fe-metal ion (with t_2g⁴e_g² electronic configuration). In order to assess the effect of addition of phenyl moieties on parent macrocyclic complex A, the UV-Vis spectra of complex A and B was recorded in ethanol using 10^− 3 M concentration of each complex, separately (Fig. 2b). The complex A demonstrated two absorption bands at 30487 and 27624 cm^− 1, which can be attributed to ⁵E_g(D) → ⁵B^1g(F) and ⁵E_g(D) → ⁵A_1g electronic transitions, respectively. While complex B also showed two absorption bands at 30120 and 25839 cm^− 1 corresponding to ⁵E_g(D) → ⁵B^1g(F) and ⁵E_g(D) → ⁵A_1g electronic transitions, respectively. However, the band at 387 nm displayed remarkable bathochromic shift with simultaneous increment in macrocyclic framework conjugation (i.e. increase in number of phenyl moieties).

Table 1

Analytical data and physical properties of complex A and B
Macrocyclic complex	Color	M.P. (^oC)	% Analysis (Calc. &Obsd.)			Molar Cond. (ohm^− 1cm² mol^− 1)	M. Wt.
Macrocyclic complex	Color	M.P. (^oC)	C	H	N	Molar Cond. (ohm^− 1cm² mol^− 1)	M. Wt.
[FeN₄C₂₂H₂₄] (A)	dark brown	178	66.01 (66.17)	6.04 (6.15)	14.00 (14.04)	46	400.3
[FeN₄C₃₀H₂₈] (B)	brown	175	72.00 (71.77)	5.64 (5.48)	11.22 (11.02)	51	500.4

In addition, both the complexes displayed molar conductance in the range of 45–52 ohm^− 1cm^− 2 mol^− 1 in DMSO solution (10^− 3 mole dm^− 3) at room temperature, indicating their electrolytic nature [17–19].

Furthermore, the molecular ion peak in positive mode of the complexes A and B was found to be at m/z 400, and 500 m/z, respectively, as shown in their corresponding mass spectra Fig. 2c. The results of the above analytic techniques are in well-agreement with the proposed structure of the complexes with the molecular formula [ML]X₂, where M = Fe(II), L = macrocyclic ligand, and X = Cl [19].

3.2. Theoretical Calculations

Density functional theory (DFT) was exploited in order to elaborate and establish the structure of complex A and B. Geometry optimization in the gaseous state was performed using default convergence circumstances using the hybrid functional B3LYP and the basis sets 6-31G* for C, H, N, and SDD for the Fe-atom [20]. The suggested structure of the complexes was theoretically simulated to determine its ground state conformation for every possible spin state. In the beginning, we worked on optimizing the geometry of these complexes, and found that they had a saddle shape geometry (D_4h). The optimized structures of complex A and B are illustrated in Fig. 3(a-b). The steric repulsion between the benzene rings and methyl units of acetyl acetone backbone might have the significant role for the "saddle shape" structure of the complexes. To alleviate the steric repulsion, the macrocyclic framework's most easily deformed C-N bonds got twisted, thus a nonplanar structure was generated due to modification of ring shape. In addition, the highest occupied molecular orbital (HOMO) of the complex A and B has an energy of -6.313 eV and − 6.621 eV, respectively. The optimized HOMO structures of the complexes are shown in Fig. 3(a-b).

3.3. Electrochemical Investigations

The prepared complexes A and B were then subjected to electrochemical evaluation in ethanol containing 0.1 M TEAP (as supporting electrolyte) and 10^− 3 M of complex A and B, separately, using cyclic voltammetry [21, 22]. Both the complexes exhibited nearly similar voltammetric responses as shown in Fig. 4. The cyclic voltammogram (CV) of complex A displayed one redox response corresponding to the Fe^+ 3/Fe^+ 2 redox transition with formal potential of -0.51 V vs Ag/AgCl (Fig. 4a). The peak current ratio (i_pa/i_pc) of 0.96 for this redox couple indicated that it was a quasi-reversible redox process. On the other hand, the CV of complex B displayed Fe^+ 3/Fe^+ 2 redox couple at a formal potential of -0.48 V vs Ag/AgCl, having the i_pa/i_pc value of 0.98, followed by quasi-reversible redox process (Fig. 4b). However, complex B displayed the anodic shift of 30 mV for the Fe^+ 3/Fe^+ 2 redox potential as compared to complex A.

To justify the anodic shift in the formal potential of Fe^+ 3/Fe^+ 2 redox transition for complex B, we investigated the charge density profile of both complexes (A and B) via DFT calculations. The results indicated that the electron density on Fe-atom was higher in complex B compared to complex A, as illustrated in Fig. 4(c-d). This fact can be explained by the concept of delocalization of pi electrons in the macrocyclic frameworks. The complex A was simple one and was having [14]-membered macrocyclic core, but in the complex B, two phenyl moieties got introduced, leading to extended conjugation. The aromatic moieties in complex A resulted higher electron density on metal ion through N-atoms via conjugation of pi electrons in comparison to complex B [23]. However, complex B possessing two additional benzene ring in its macrocyclic framework should have higher electron density on metal than complex A, but benzene ring being more aromatic than naphthalene, the metal atom of complex B would have less electron density [24]. On the other hand, it is known fact that Fe^+ 3/Fe^+ 2 redox couple represent ‘eg energy level’ of Fe metal ion, therefore less electron density on Fe-central metal ion of macrocyclic complex B would result to down-shift in ‘eg orbital energy’ (as supported by DFT calculations), displaying anodic shift in Fe^+ 3/Fe^+ 2 formal potential [11].

3.4. Biological activity:

All the prepared complexes were evaluated for their antimicrobial potential using agar well diffusion (AWD) method. These complexes along with microbial culture were accustomed to 0.5 McFarland standard equivalent to 1.5 × 10⁸ cfu/mL microbial pathogen suspension (approx.). Each petri plate received 25 mL of Agar media and was swabbed with 100 µL inoculums of the test microorganisms. After 20 min, a 6 mm well got cut at the center of agar plates and each well were filled with prepared samples of synthesized complexes, keeping solvent media having Gentamycin as + ive control and solvent media alone as –ive control. Each plate was analyzed for measuring the zone of inhibition after 20 hr of incubation at 37 ^ᵒC and for fungus, zone of inhibition was measured after incubation for 48 hr at 28^ᵒC [25–27].

Antimicrobial activity of synthesized complexes was calculated by measuring the zone of inhibition against the test organisms with zone reader (Hi Antibiotic Zone Scale). The complex A (with 1000 ppm concentration %) showed maximum zone of inhibition against B. subtilis (22 mm) followed by S. aureus (14 mm), E. coli (15 mm) and P. aeruginosa (16 mm). Similarly, complex B (with 1000 ppm concentration %) also exhibited maximum zone of inhibition against B. subtilis (21 mm) followed by E. coli (16 mm) and S. aureus (16 mm), P. aeruginosa (15 mm). Against fungal pathogen C. albicans, complex A was found to be the most effective (20 mm) followed by complex B (18 mm). Figure 5a and 5b showed the concentration-dependent antimicrobial activity inhibition zone against the B. subtilis pathogen for complex A and complex B. Table 2 shows a comparison of the antibacterial activity of the complex A and B with previously reported potential macrocyclic complexes.

Table 2

A comparison of the antibacterial activity of the complex A and B with previously reported macrocyclic complexes.
Macrocyclic Complexes	Diameter of the zone of inhibition (mm) (conc. in µg.mL^− 1)					Ref.
Macrocyclic Complexes	E. coli	P. aeruginosa	B. subtilis	S. aureus	C. albicans	Ref.
Tetraaza-complex	13	13	12	13	12	[28]
Tetraaza-complex	19	24	18	28	-	[29]
Tetraaza-complex	12	12	12	12	11	[30]
Tetraaza-complex	14	12	14	10	18	[31]
Tetraaza-complex	9	9	10	12	13	[32]
Tetraaza-complex	18	12	18	15	12	[33]
Tetraaza-complex	-	22	-	14	24	[34]
Tetraaza-complex-A	15	16	22	14	20	This Work
Tetraaza-complex-B	16	15	21	16	18	This Work

In this work, two N₄-macrocyclic complexes A and B with comparable molecular cores but distinct phenyl moieties were synthesized utilizing a template procedure and characterized using several characterization techniques. Characterization studies revealed that both the complexes had a saddle-shaped octahedral structure. According to theoretical studies, the nonplanar structure of the macrocyclic framework was created by the interactions between benzenes and amidic moieties in the macrocyclic framework, resulting in the twisting of torsional angles around the C-N moieties. The results of electrochemical investigation showed the interesting correlation between both the complexes, in terms of anodic shift of Fe^3+/2+ redox potential with the increment in conjugation. A 30 mV anodic shift in Fe^3+/2+ redox potential for complex B was observed as compared to complex A. Because of enhanced phenyl conjugation, the highest occupied molecular orbital was found to move down, that might be linked back to the anodic shift in the redox potential of Fe^3+/2+, as supported by DFT calculations. Therefore, both the complexes can be used as redox models in a variety of electrochemical applications. In addition, biological studies suggest that complex A and B have significant promise against a variety of pathogens.

Acknowledgments

The authors are thankful to GLA University, Mathura to provide the infrastructural support for the completion of this study.

Conflict of Interest

We have no conflict of interest

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No competing interests reported.

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Editorial decision: Major revision
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You are reading this latest preprint version

Phenyl Conjugation Effect on Fe 3+/2+ Formal Potential of FeN 4 -macryclic Complex

Status:

Journal Publication

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Abstract

Figures

Introduction

Experimental Section

2.1. Materials and methods

2.1. Preparation of the macrocyclic complexes A and B

Result And Discussion

3.1. Synthesis and Characterization

3.2. Theoretical Calculations

3.3. Electrochemical Investigations

3.4. Biological activity:

Conclusions

Declarations

References

Additional Declarations

Status:

Journal Publication

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