*3.1. Preapprehension*

The attachment of the receptor to drugs does not affect the efficiency of its work, in fact, it improves it. However, it should be noted that different drugs have varying efficacy when they are connected with the receptor's site [41–45]. Several reports showed differences in the efficacy of two drugs targeting the same receptor because the activation of the receptor is dependent on the rate of drug interaction with the receptor [43,44].

This drew pharmacologists' attention to the importance of knowing the relationship between drug chemical composition and physiological action. These findings may aid our understanding of the molecular nature of drug–receptor interactions [43,44].

In many cases, the drug's binding to the receptor seems to have low energy, certainly lower than that involved in conventional covalent bonding [45]. Ionic association, particularly hydrogen bonding, and other weaker forces such as charge–transfer forces, or a combination of many of these forces, can produce what is termed "receptor-drug complexing". The capacity of drugs and related compounds to form charge–transfer complexes with well-defined electron acceptors or electron donors, primarily in non-aqueous circumstances, is used as a primary criterion for determining whether charge–transfer forces are manipulated in any way [46–49].

The λmax of UV–Vis spectra of the synthesized charge–transfer complexes were found to be at 340 and 436 nm for (SRX)(PA), 351 nm for (SRX)(DNB), 353 nm for (SRX)(*p*BBA), 528 nm for (SRX)(DCQ), 540 nm for (SRX)(DBQ), and lastly 745 and 833 nm for (SRX)(TCNQ). According to photometric titration measurements, the produced charge–transfer complexes between SRX and corresponding π-acceptors had a 1:1 molar ratio. The dative structure D+–A of charge–transfer complexes in polar solvents were shown to be destabilized by the dissociation of charge–transfer complexes into D+ and A [50–53].

In pharmacokinetics, examining the physical and chemical properties of pharmacological substances in solution, as well as their mechanism of action, is critical. Spectroscopic and thermodynamic approaches are used to assess the binding strength of pharmaceutical compounds to other substances in living systems [41]. In biological and bioelectrochemical energy transfer processes, electron acceptor complexes (EDA) are a common occurrence [42]. The development of highly colored charge–transfer complexes is often related to molecular interactions between electron donors and acceptors, which absorb light in the visible area [48].

Electron acceptor complexes with ionic bands are the most prevalent. Ionic interactions and structural recognition are two crucial mechanisms in biological systems. For example, drug action, enzyme activation, and ion transport across lipophilic membranes are all intricate [45]. Ionic interactions are the fundamental outputs of selectivity, rate control, and reversibility in many biological systems [46].

The most commonly used procedures for assessing various drugs and sophisticated charge transfer investigations include UV direct spectrophotometry [47], colorimetry [48], and HPLC [49]. EDA compounds, as previously reported, have good nonlinear optical properties and electrical conductivity [54].

The six charge–transfer complexes were expected to have particle sizes of 50 nm for (SRX)(PA), 25 nm for (SRX)(DNB), 5 nm for (SRX)(*p*NBA), 10 nm for (SRX)(DCQ), 20 nm for (SRX)(DBQ), and 5 nm for (SRX)(DBQ) (TCNQ). These findings were based on TEM

scans, which showed that the particles of the manufactured charge–transfer were nanoscale in size. The simultaneous thermal stability on the TG/DTG curves of all charge–transfer complexes at a heating rate of 10 °C/min in a static nitrogen atmosphere are shown in Figure 3. The overall mass loss from the TGA curves was 78.17% for SRX–PA, 58.38% for SRX–

scans, which showed that the particles of the manufactured charge–transfer were na-

*Molecules* **2022**, *27*, x 6 of 21

noscale in size.

The simultaneous thermal stability on the TG/DTG curves of all charge–transfer complexes at a heating rate of 10 ◦C/min in a static nitrogen atmosphere are shown in Figure 3. The overall mass loss from the TGA curves was 78.17% for SRX–PA, 58.38% for SRX–DNB, 50.45% for SRX-p-NBA, 69.40% for SRX–DCQ, 77.58% for SRX–DBQ, and 75.69% for the SRX–TCNQ complexes. The complexes had mass losses of one to three maxima peaks. The thermal analysis of the curves of the [(SRX)(π-acceptor)] CT complexes clearly shows that the maximum DTG peaks are located at 415, 230, 357, 383, 343, and 370 ◦C, respectively. DNB, 50.45% for SRX-p-NBA, 69.40% for SRX–DCQ, 77.58% for SRX–DBQ, and 75.69% for the SRX–TCNQ complexes. The complexes had mass losses of one to three maxima peaks. The thermal analysis of the curves of the [(SRX)(π-acceptor)] CT complexes clearly shows that the maximum DTG peaks are located at 415, 230, 357, 383, 343, and 370 °C, respectively.

**Figure 3.** TGA curves of (1:1) charge-transfer complexes [(SRX)(π-acceptor)].

**Figure 3.** TGA curves of (1:1) charge-transfer complexes [(SRX)(π-acceptor)].

The Coats-Readfern and Horowitez-Metzegar methods [55,56] were used to collect the kinetic thermodynamic data of the maximal DTG peak decomposition steps of all charge– transfer complexes. The kinetic parameters, *E*, *A*, ∆*S*, ∆*H*, ∆*G*, and *r* were calculated, and the data are listed in Table 1 and displayed in Figure 4.


**Table 1.** Kinetic thermodynamic parameters for the six charge–transfer complexes based on Coats– Redfern (CR) and Horowitz–Metzger (HM) methods.

**Figure 4.** Kinetic curves of (1:1) charge-transfer complexes [(SRX)(π-acceptor)] using (**a**) Coats-Readfern and (**b**) Horowitez-Metzegar methods. **Figure 4.** Kinetic curves of (1:1) charge-transfer complexes [(SRX)(π-acceptor)] using (**A**) Coats-Readfern and (**B**) Horowitez-Metzegar methods.

**Δ***G* **(kJ mol−1)**

**Δ***H* **(kJ mol−1)** 

**Table 1.** Kinetic thermodynamic parameters for the six charge–transfer complexes based on Coats–

*E* **r** 

**Parameter** 

**(J mol−1 K−1)** 

HM 11.2 × 104 5.60 × 109 −6.32 × 101 1.12 × 105 1.50 × 105 0.9989

HM 8.65 × 104 1.34 × 105 −1.30 × 102 8.12 × 104 1.44 × 105 0.9989

HM 7.23 × 104 1.22 × 104 −1.56 × 102 6.71 × 104 1.54 × 105 0.9985

HM 5.22 × 104 1.85 × 106 −1.32 × 102 4.68 × 104 9.22 × 104 0.9987

HM 6.35 × 104 2.75 × 104 −1.72 × 102 5.90 × 104 1.40 × 105 0.9994

(SRX)(PA) CR 11.5 × 104 4.00 × 108 −8.52 × 101 1.12 × 105 1.54 × 105 0.9990

(SRX)(DNB) CR 7.80 × 104 1.50 × 105 −1.55 × 102 7.25 × 104 1.47 × 105 0.9980

(SRX)(*p*NBA) CR 6.38 × 104 1.32 × 104 −1.72 × 102 5.90 × 104 1.51 × 105 0.9995

(SRX)(DCQ) CR 4.80 × 104 1.25 × 105 −1.45 × 102 4.43 × 104 9.40 × 104 0.9943

(SRX)(DBQ) CR 5.77 × 104 5.12 × 103 −1.85 × 102 5.22 × 104 1.45 × 105 0.9890

Redfern (CR) and Horowitz–Metzger (HM) methods.

**(kJol−1)** *A* **(s−1) Δ***<sup>S</sup>*

**Complex Method** 

The activation energies of the [(SRX)(π–acceptor)] CT complexes in the case of the maximum DTG peak decomposition step were as follows: (SRX)(TCNQ) > (SRX)(PA) > (SRX)(DNB) > (SRX)(*p*NBA) > (SRX)(DBQ) > (SRX)(DCQ). Among the six π–acceptors, it was found that the SRX–TCNQ and SRX–PA complexes had greater activation energies than the other charge–transfer complexes. This is

The activation energies of the [(SRX)(π–acceptor)] CT complexes in the case of the

#### (SRX)(TCNQ) > (SRX)(PA) > (SRX)(DNB) > (SRX)(*p*NBA) > (SRX)(DBQ) > (SRX)(DCQ). owing to the presence of cyano and nitro groups in the TCNQ and PA acceptors [57].

Among the six π–acceptors, it was found that the SRX–TCNQ and SRX–PA complexes had greater activation energies than the other charge–transfer complexes. This is owing to the presence of cyano and nitro groups in the TCNQ and PA acceptors [57]. *3.2. UV–Vis Spectra and Photometric Titration*  The UV-Vis spectra of the six charge–transfer complexes in methanol solvent were investigated in the 200–900 nm range (Figure 5) [4]. These charge–transfer complexes are

formed by combining 1.00 mL of 0.5 mM from the SRX drug donor with different volumes

#### *3.2. UV–Vis Spectra and Photometric Titration* of the six π-electron acceptors to reach a final concentration of 0.5 mM. With methanol as

*Molecules* **2022**, *27*, x 8 of 21

(SRX)(TCNQ) CR 11.1 × 104 6.22 × 108 −8.14 × 101 9.72 × 104 1.33 × 105 0.9984

maximum DTG peak decomposition step were as follows:

HM 11.8 × 104 5.50 × 109 −6.35 × 101 1.12 × 105 1.42 × 105 0.9996

The UV-Vis spectra of the six charge–transfer complexes in methanol solvent were investigated in the 200–900 nm range (Figure 5) [4]. These charge–transfer complexes are formed by combining 1.00 mL of 0.5 mM from the SRX drug donor with different volumes of the six π-electron acceptors to reach a final concentration of 0.5 mM. With methanol as the solvent, each charge–transfer system had a total volume of 5 mL. Absorption bands for [(SRX)(PA), [(SRX)(DNB)], [(SRX)(p-NBA)], [(SRX)(DCQ)], [(SRX)(DBQ)], and [(SRX)(TCNQ)] donor–acceptor interaction systems appeared at λmax of 436 nm, 351 nm, 353 nm, 528 nm, 540 nm, and 745 nm, respectively. At 25 ◦C, photometric titrations were performed with the SRX medication as an electron donor and the six π–electron acceptors. The molar ratio of the produced charge–transfer complexes between SRX and the corresponding π–electron was 1:1. The photometric titration curves for the maximal charge–transfer absorption bands (λmax) are shown in Figure 6 [4]. the solvent, each charge–transfer system had a total volume of 5 mL. Absorption bands for [(SRX)(PA), [(SRX)(DNB)], [(SRX)(p-NBA)], [(SRX)(DCQ)], [(SRX)(DBQ)], and [(SRX)(TCNQ)] donor–acceptor interaction systems appeared at λmax of 436 nm, 351 nm, 353 nm, 528 nm, 540 nm, and 745 nm, respectively. At 25 °C, photometric titrations were performed with the SRX medication as an electron donor and the six π–electron acceptors. The molar ratio of the produced charge–transfer complexes between SRX and the corresponding π–electron was 1:1. The photometric titration curves for the maximal charge– transfer absorption bands (λmax) are shown in Figure 6 [4]. The photometric titration findings were obtained by graphing the absorbance (Yaxis) against the ratio of indicated acceptors (X-axis) using established procedures [4]. The molar ratio of the produced charge–transfer complexes between SRX medication and identified–acceptors is 1:1 (Figure 6).

**Figure 5. Figure 5.** UV–Vis spectra curves of the SRX with the six π–acce UV–Vis spectra curves of the SRX with the six π ptors complex [4]. –acceptors complex [4].

The photometric titration findings were obtained by graphing the absorbance (Y-axis) against the ratio of indicated acceptors (X-axis) using established procedures [4].

The molar ratio of the produced charge–transfer complexes between SRX medication and identified–acceptors is 1:1 (Figure 6).
