DFT Study of Charge Transfer Complexes Between Norfloxacin and Ciprofloxacin Drugs with Picric Acid and 3,5-Dinitrobenzoic Acid Acceptors

doi:10.21203/rs.3.rs-4613769/v1

This work reports density functional theory (DFT) calculations on the molecular structures, electronic distribution, electric moments, thermodynamic parameters, molecular electrostatic map, nonlinear optical activity, and UV-vis and IR spectroscopy analysis of charge transfer complexes between norfloxacin and ciprofloxacin, as electron-donors and π-electron-acceptors, namely picric acid and 3,5-dinitrobenzoic acid, formed in the gas phase at the B3LYP/6-311‏‏G (d,p) method/basis sets. Good correspondence was generally obtained between the calculated parameters and the experimental ones.

Health sciences/Biomarkers

Physical sciences/Chemistry

Charge transfer complex

DFT

electron acceptor

electron donor

norfloxacin

and ciprofloxacin

Quantum mechanical computations, specifically density functional theory (DFT) calculations, have demonstrated their capability to replicate and explain the experimental parameters of charge transfer complex (CTC) formation. The CTC, also known as the donor-acceptor complex, is a combination of two or more molecules in which the bonding is created by an electronic transition to an excited electronic state resulting in the transfer of some electronic charge between the molecules. The donor-acceptor complex is stabilized by the resulting electrostatic attraction. The electron donor is the molecule that transfers the charge, while the electron acceptor is the molecule that receives it. The attraction found in a CTC is not a strong chemical bond like a covalent bond. Numerous research papers, both experimental and theoretical, about CTCs can be found in the literature [1–6]. Ganesh and colleagues studied the computed tomography characteristics of 1,4-benzoquinone compounds incorporating L-phenylalanine in a water-based solution [7]. Several spectral techniques were utilized to experimentally investigate the formation of the complex. The DFT/B3LYP calculations provided strong support for the observed trend in the association constants of these complexes. Mostafa et al. created two novel CT complexes, procainamide-chloranilic acid, and procainamide-DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone), using procainamide as the electron donor and chloranilic acid and DDQ as the electron acceptors [8]. The FTIR, NMR, and various spectroscopic techniques were used to determine the structures of these two CT complexes. A stability study of each complex was carried out for the first time using different spectroscopic parameters. The spectrophotometric determination confirmed the presence of CTCs in the solution. The spectrophotometric titration method was used to determine the molecular composition of each complex, revealing a 1:1 ratio between donor and acceptor. DFT calculations were conducted at the ωB97XD/6-311 + + G (2d, p) level of theory to analyze the non-covalent interactions of the complexes. The interaction energies calculated using DFT and the Gibbs free energies showed a similar order to what was found in experimental observations. Manna et al. utilized quantum mechanical calculations to analyze the structural and electronic characteristics of CTCs formed by fullerene derivatives C60 and C70 with azulene and its derivatives. They determined that the fullerene moiety contains the localized LUMO, whereas the azulene contains the localized HOMO [9]. Shukla and colleagues examined the ground state structure and charge transfer transitions of a paracetamol and chloranil complex through theoretical analysis with DFT and TD-DFT techniques. TD-DFT computations were employed to investigate the observed UV-vis spectrum of this CT compound; these computations validated the CT transition [10].

M. S. Refat and colleagues investigated the formation of CTCs between norfloxacin (nor) and ciprofloxacin (cip) drugs as donors and picric acid (PA) and 3,5-dinitrobenzoic acid (DNBA) as π-acceptors using spectrophotometry in methanol at room temperature [11]. The findings showed the creation of CT complexes with a 1:1 molar ratio between the donor and acceptor at maximum CT bands. Formation constant (K_CT), molar extinction coefficient, standard free energy (ΔG^o), oscillator strength (f), transition dipole moment (l), resonance energy, and ionization potential were all calculated. IR, HNMR, UV-visible spectrophotometry, elemental analysis (CHN), and thermo-analytical techniques (TG-DTG) were employed to analyze the composition of CTCs. It suggests that the charge transfer (CT) process resulted in protons moving from the acceptors to either nor or cip donors, leading to the formation of an intermolecular hydrogen bond. Nonetheless, this research lacked theoretical calculations to explain and enhance the experimental findings. Thus, the present report aims to report quantum chemical calculations including geometric structures, Mulliken electronic charges, thermochemical parameters, number of electrons transferred, difference frontier molecular orbital energies, ∆E_g, molecular electrostatic potential (MEP) plots, vibrational modes, transition energies, average polarizability, and first hyperpolarizability values using DFT/B3LYP and TD-DFT methods with the 6-311G (d, p) extended basis sets for these three CT complexes.

The Gaussian 09 suite of programs was utilized for all calculations [12]. DFT was utilized for conducting geometry optimizations with Becke's three-parameter exchange functional [13, 14], the Lee-Yang-Parr correlation functional (B3LYP), and the 6-311G (d, p) basis set, where d-type orbitals were added to all atoms excluding hydrogen atoms, and p-type orbitals were added to hydrogen atoms. In geometry optimizations, each bond length, bond angle, and dihedral angle was able to relax without any restrictions. Vibrational frequency analysis was used to confirm the nature of the stationary points, making sure that only real frequency values were obtained for all geometries, indicating minima on the potential energy surface. The CTCs' transition energies were computed using single-point TD-DFT with optimized geometries at the B3LYP/6-311G (d, p) level of theory. GuassView program (version 6) was used for visual inspection [15]. Geometry optimizations were carried out on the ground states of the donor and acceptor molecules without any constraints. The geometry of the resulting CTC was built by combining the optimized geometries of donor and acceptor molecules. The final shapes were once more fine-tuned without any limitations using the identical technique and foundation.

Optimized geometries

Figure 1 displays the optimized molecular structures of the CT complexes, free drugs, 3,5-dinitrobenzoic acid (DNBA), and picric acid (PA) in the gas phase, as well as the atomic numbering system utilized in this investigation. The optimized geometries of the donors and acceptors are aligned parallel to each other, re-optimized, and allowed to relax unconstrained. Therefore, the positioning of the two elements within the CTC shows a noticeable discrepancy compared to their initial positioning (before the optimization procedure). The complex formation between the donor and acceptor molecules is due to intermolecular H-bonding when they come close to each other. According to Fig. 1, hydrogen bonds are typically weak (OH bond length is between 1.287–1.574 Å), but the quantity of potential H-bonds influences the stabilization of CTCs. In [(cip)(PA)], [(nor)(PA)], and [(nor)(DNBA)] complexes, only one kind of hydrogen bonding is present. In the CTCs, drug molecules appear to come towards the acceptor molecule via the secondary nitrogen atom. Therefore, the donor molecule's approach through the NH group may indicate that this nitrogen atom serves as the primary donation center for the drugs (as donor molecules). Tables 1 and 2 provide bond distances of nor or cip drugs, PA and DNBA, and CT-complexes optimized in the gas phase using B3LYP/6-311G (d, p). After forming complexes, only a small number of bond lengths stayed constant, while the majority of bond lengths were altered. Certain bonds are lengthened while others are contracted. These findings can be viewed as proof of the CT process, which has been noted in other studies before [16, 17].

The bond lengths of C21N20, C22N21, and C20N21 bonds in [(cip)(PA)], [(nor)(PA)], and [(nor)(DNBA)] complexes are 1.491 Å, 1.477 Å, and 1.476 Å, respectively. The bond length between PA and cip molecules falls within the range of 0.967–1.480 Å. Furthermore, when complexed, more bonds are shortened than bonds that are lengthened, possibly because of the process of charge donation. Table 2 displays the bond lengths of the [(cip)(PA)], [(nor)(PA)], and [(nor)(DNBA)] complexes optimized in the gas phase using B3LYP/6-311G (d, p) method. There was no significant change in bond lengths for donors and acceptors upon complexation, only a few bonds were elongated or shortened. More proof for the CT process was given by calculating the change in Mulliken charge for selected atoms when transitioning from a free donor/acceptor molecule to the complex, as shown in Table 3.

Table 1

Selected optimized bond lengths (Å) of PA, DNBA, cip, nor compounds in the gas phase.
Ligand	Parameter	Bond length (Å)	Ligand	Parameter	Bond length (Å)
cip	C6-O16	1.221	nor	C5-C6	1.477
	C17- N3	1.449		C6-O7	1.377
	C12-F15	1.356		C6-O8	1.202
	C11-N14	1.398		C9-O10	1.221
	C7-O8	1.376		C13-F14	1.358
	C7-O9	1.202		C17-N3	1.405
	C1-C2	1.368		C2-N3	1.472
	C2-N3	1.357		C15-N18	1.396
	C4-N3	1.407		C4-C5	1.370
	C18-N14	1.475		C23-N18	1.467
	C22-N14	1.461		C19-N18	1.468
	C19-N20	1.463		C20-N21	1.460
	C21-N20	1.463		C22-N21	1.462
	N20-H23	1.016		O7-H30	0.967
DNBA	C2-O1	1.353	PA	C6-N8	1.465
	C2-O3	1.205		C1-O7	1.315
	O1-H16	0.967		C4-N14	1.477
	N11-O12	1.229		N14-O15	1.221
	N11-O13	1.226		N14-O16	1.221
	C8-N11	1.477		C2-N11	1.482
	C6-N10	1.480		N11-O12	1.222
	N10-O14	1.228		N11-O13	1.216
	N10-O15	1.227		O7-H19	0.987

Table 2

Selected optimized bond lengths (Å) of [(cip)(PA)], [(nor)(PA)], and [(nor)(DNBA)] complexes in the gas phase.
CT-Complex	Parameter	Bond length (Å)	CT-Complex	Parameter	Bond length (Å)
[(cip)(PA)]	C6-O16	1.219	[(nor)(DNBA)]	C20-N21	1.476
	C17-N3	1.450		C19-N14	1.470
	C12-F15	1.356		C23-N14	1.460
	C11-N14	1.409		C11-N14	1.394
	C7-O8	1.374		C12-F15	1.358
	C7-O9	1.201		C2-N3	1.354
	C1-C2	1.368		C4-N3	1.405
	C2-N3	1.359		C17-N3	1.478
	C4-N3	1.404		C7-O8	1.376
	C18-N14	1.469		C7-O9	1.202
	C22-N14	1.457		C1-C2	1.370
	C19-N20	1.492		C6-O16	1.221
	C21-N20	1.491	[(nor)(PA)]	N38-O40	1.221
	N20-H23	1.098		C22-N21	1.477
	O27-H23	1.444		C27-O26	1.252
	C28-O27	1.259		C32-N33	1.461
	C33-N34	1.472		C28-N36	1.459
	N34-O37	1.225		N33-O34	1.224
	N34-O38	1.222		C7-O8	1.375
	C29-N35	1.454		C7-O9	1.202
	N35-O39	1.222		C1-C2	1.372
	N35-O40	1.239		C1-C7	1.478
	C31-N36	1.463		C2-N3	1.352
	N36-O41	1.225		C4-N3	1.402
	N36-O42	1.225		N33-O35	1.232
	N8-O9	1.243		N36-O37	1.221
	N8-O10	1.212		N36-O38	1.237
[(nor)(DNBA)]	O26-H24	1.287		N39-O40	1.225
	N21-H24	1.091		N39-O41	1.225
	C27-O26	1.323		O26-H24	1.574
	C27-O28	1.216		N21-H24	1.068
	C29-C27	1.502		C10-N3	1.484
	C33-N35	1.485		C14-N18	1.410
	N33-O36	1.221		C23-N18	1.455
	N35-O37	1.221		C19-N28	1.462
	C31-N38	1.485		C15-F17	1.375
	N38-O39	1.221		C6-O12	1.221

Mulliken electronic charge

In small split valence, basis sets like the one in this research, Mulliken population analysis provides chemically intuitive charge signs on atoms and typically gives reasonable charge magnitudes [18]. With only a few exceptions, noticeable differences can be seen in Mulliken charge distribution on various atoms when comparing free species to the created complex. This is a clear indication of the charge transfer process from the donor molecule to the acceptor molecule and from the acceptor back to the donor molecule in the CT back-donation process. Moreover, the electron deficiencies on carbon, nitrogen, oxygen, and fluorine atoms are equal in charge-transfer complexes of [(cip)(PA)], [(nor)(PA)], and [(nor)(DNBA)]. The rise in Mulliken charges in certain atoms of electron-acceptor molecules, coupled with the decline in Mulliken charges in certain atoms of electron-donor molecules, provides strong proof of reactivity traits in these species.

Table 3

Mulliken electronic charge on atoms of [(cip)(PA)], [(nor)(PA)], and [(nor)(DNBA)] complexes.
[(nor)(PA)]		[(cip)(PA)]		[(nor)(DNBA)]
Atom	Charge	Atom	Charge	Atom	Charge
C1	-0.403	C1	-0.400	C1	-0.402
C2	0.268	C2	0.264	C2	0.264
C4	0.297	C4	0.312	C4	0.305
C5	-0.248	C5	-0.261	C5	-0.256
C6	0.397	C6	0.392	C6	0.397
C7	0.421	C7	0.422	C7	0.420
C10	-0.080	C10	-0.114	C10	-0.131
C11	-0.354	C11	0.103	C11	0.145
C13	-0.092	C12	0.282	C12	0.257
C14	0.059	C13	-0.050	C13	-0.056
C15	0.275	C17	-0.075	C17	-0.064
C16	-0.054	C18	-0.086	C18	-0.359
C19	-0.103	C19	-0.091	C19	-0.102
C20	-0.120	C21	-0.095	C20	-0.084
C22	-0.136	C22	-0.082	C23	-0.122
C23	-0.123	C25	-0.202	C27	0.445
C27	0.299	C26	-0.239	C29	-0.258
C32	0.053	C28	0.298	C30	0.044
C31	0.030	C29	0.047	C31	0.109
C30	0.079	C30	0.015	C32	0.015
C29	0.024	C31	0.083	C33	0.108
C28	0.038	C32	0.037	C34	0.053
H25	0.261	C33	0.051	H24	0.306
H42	0.158	H23	0.360	H25	0.223
H43	0.252	H24	0.251	H41	0.155
H44	0.159	H43	0.150	H42	0.251
H46	0.135	H44	0.254	H43	0.122
H47	0.124	H45	0.138	H45	0.136
H48	0.135	H46	0.130	H46	0.136
H49	0.140	H47	0.155	H47	0.129
H50	0.127	H48	0.166	H48	0.136
H51	0.168	H49	0.111	H49	0.136
H52	0.129	H50	0.169	H50	0.155
H53	0.176	H51	0.163	H52	0.132
H54	0.157	H52	0.167	H53	0.132
H55	0.147	H53	0.160	H54	0.133
H56	0.204	H54	0.149	H55	0.124
H57	0.156	H55	0.115	H56	0.133
H58	0.141	H56	0.133	H57	0.137
H59	0.166	H57	0.149	H58	0.156
H60	0.163	H58	0.152	H59	0.173
O8	-0.371	H59	0.143	H60	0.155
O9	-0.302	H60	0.163	O8	-0.375
O12	-0.310	H61	0.161	O9	-0.300
O26	-0.475	O8	-0.371	O16	-0.310
O34	-0.261	O9	-0.296	O26	-0.366
O35	-0.288	O16	-0.302	O28	-0.368
O37	-0.254	O27	-0.476	O36	-0.256
O38	0.331	O37	-0.265	O37	-0.253
O40	-0.275	O38	-0.268	O39	-0.254
O41	-0.274	O39	-0.259	O40	-0.253
N3	-0.517	O40	-0.344	N3	-0.521
N18	-0.415	O41	-0.273	N14	-0.431
N21	-0.333	O42	-0.277	N21	-0.495
N33	0.186	N3	-0.483	N35	0.178
N39	0.171	N14	-0.463	N38	0.177
N36	0.192	N20	-0.373	F15	-0.239
F17	-0.239	N34	0.179
		N35	0.187
		N36	0.170
		F15	-0.235

Thermodynamic parameters

The energy of interaction (the stabilization energy) between two molecular fragments is determined by comparing their combined energy to the sum of their energies when isolated. Isolation can be compared to an endless gap between those fragments. To determine the interaction energy, three energy calculations must be carried out: one on the CTC and one on each fragment. The interaction energy can be determined by subtracting the individual energies from the complex energy. In this formulation, quantum mechanical calculations with basis sets are affected by an error called basis set superposition error (BSSE). When the electron orbitals on separate fragments are not defined using the same basis functions as when they are calculated together, a basis set mismatch occurs, causing higher energies for the isolated fragments due to the use of a smaller basis set. BSSE is typically fixed through counter-poise correction, involving the addition of a second fragment as ghost atoms with basis functions but no charge or electrons, to ensure the basis set aligns with the complete molecule calculation. Table 4 provides a summary of various thermodynamic parameters such as interaction energy, enthalpy, entropy, Gibbs free energy, and correction for vibrational zero point energy for the complex formation in the gas phase as calculated using B3LYP/6-311G(d, p). The complexes [(cip)(PA)], [(nor)(PA)], and [(nor)(DNBA)] exhibit greater stability when compared to their components (ΔE_int<0) for the CTCs. The complexes are more secure than the individual components, with values of -304.190 kcal/mol, -301.082 kcal/mol, and − 305.002 kcal/mol, respectively. [(nor)(DNBA)] has the highest E_int for the formation of the CTCs in this group of complexes. Regarding additional thermodynamic parameters, the interaction enthalpies of the analyzed CT complexes fall within negative values (range − 301.67−(-305.59) kcal/mol).

Based on the calculations conducted on all the complexes examined, the Gibbs free energy change (ΔG°) is a negative value resulting from the exothermic and spontaneous formation of the complex. Furthermore, the presence of negative ΔH° and ΔG° values suggests a significant interaction among the reactants. However, as entropy rises, disorder and the stability of the complex also increase. Hence, the outcomes of thermodynamic factors demonstrate a spontaneous creation of a complex and the ligands' capability to create a firm complex. The favorable entropy values (within 228.91-232.31 kcal/mol) and unfavorable enthalpy values in all complexes are seen as the main reasons for complex formation. The current data reveals a calculated Gibbs free energy, which aligns with findings in previous research [19]. The variances in interaction energies between complexes [(cip)(PA)], [(nor)(PA)], and [(nor)(DNBA)] can be linked to the varying ability of the donor molecule to act as a donor, which can be directly correlated to the ionization potential values of the donors [20].

Table 4

Calculated interaction energy, interaction enthalpy, interaction entropy, interaction Gibbs free energy, and correction for vibrational zero-point energy for the studied complexes in the gas phase (*kcal/mol*).
(D)(A) complex	ΔE_int	ΔH_int	ΔS_int	ΔZPVE	ΔG_int
[(nor)(DNBA)]	-305.002	-305.595	229.472	283.489	-237.178
[(nor)(PA)]	-301.082	-301.675	228.916	279.144	-233.425
[(cip)(PA)]	-304.190	-304.783	232.310	282.056	-235.521

IR analysis

Experimentally studying the IR vibrational frequencies of CTCs can be a long and inaccurate procedure. This is because the resulting spectra contain numerous bands that overlap. Thus, vibrational frequency calculations help identify spectral characteristics [21, 22]. Additionally, the animations of various vibrational modes simplify the process of assigning them. Table 5 and Fig. 2 show the simulated FT-IR absorption spectra of complexes calculated at the B3LYP/6-311G (d, p) level. Typically, the CH stretching vibrations in the region of 3000–3100 cm^− 1 are observed in the aromatic ring for CH vibrations modes. The CH values for the complexes [(cip)(PA)], [(nor)(PA)], and [(nor)(DNBA)] were determined to be in the range of 2918–3205 cm^− 1. The experimental values for vibrations in complexes [(cip)(PA)], [(nor)(PA)], and [(nor)(DNBA)] range from 2752 cm^− 1 to 3200 cm^− 1. Therefore, the average discrepancy between the calculated and experimental values is in the tens of cm^− 1 range. Using scaled vibrations can result in more precise outcomes [23]. In general, the acceptor molecules' IR bands shifted to lower values in their respective complexes. The donor molecules' IR bands were increased in frequency in their respective complexes. This finding mirrors that of previous studies, which attribute the shifts to characteristics of the CT interaction (HOMO_D-LUMO_A) [24].

For instance, CH peaks at 3088 cm^− 1 and 3200 cm^− 1 in electron-donating molecule complexes like [(nor)(DNBA)] and [(nor)(PA)], respectively. The CH helps donate electrons to the cip for the formation of complex [(cip)(PA)] around 3147 cm^− 1. The agreement between the calculated and the existing experimental values is satisfactory. In the 1475–1600 cm^− 1 range, C = C vibrations in aromatic rings are found, with computed wavenumbers ranging from 1531–1562 cm^− 1 and experimental values falling between 1535–1589 cm^− 1 (Refer to Table 5). The GaussView animation package assisted in determining the assignments of wavenumbers associated with the ring breathing mode of vibrations. It demonstrates a strong alignment with the experimental data that is currently accessible. The phenyl CH bending vibrations experimental values fall between 929 cm^− 1 and 961 cm^− 1 for the complexes, while the calculated values range from 926 cm^− 1 to 962 cm^− 1. Furthermore, the computations indicate that there is minimal variation in these quantities between the unbound and the bound forms. The complexation process did not impact these vibrations. The bending vibration modes of NH₂⁺ showed experimental values of 831–897 cm^− 1, while the calculated values for the complexes ranged from 859–939 cm^− 1. In Table 5, the stretching vibrations of the C = O group for [(cip)(PA)], [(nor)(PA)], and [(nor)(DNBA)] complexes are observed between 1622–1618 cm^− 1 experimentally and between 1613–1653 cm^− 1 calculated [25].

Table 5

Calculated and experimental selected modes of vibrations and their assignments for [(cip)(PA)], [(nor)(PA)], and [(nor)(DNBA)] complexes.
Experimental [11]			Calculated			Assignments
(nor)(PA)	(cip)(PA)	(nor)(DNBA)	(nor)(PA)	(cip)(PA)	(nor)(DNBA)	Assignments
3471 vw	3861 vw, br	3744 vw	3779	3771	3779	ν(N-H)+ν(O-H)
3442 w, br	3741 vw	3423 s,br	3481	3471	3461
	3437 w, br
3200 vw	3147 vw	3088 vw	3205	3124	3086	ν(C-H) hydrogen bond
3184 w	3062 w, br	3052 ms	3147	3099	3056
3072 m	2926 w	2972 m	3129	3088	3024
2976 vw	2835 w	2927 vw	3119	2933	3010
2844 w	2752 w	2835 m	3108	2918	2999
2762 w	2485 m	2715 w, br	3080	2215	2608
2718 w	2361 ms	2472 m	3075	1831	1828
2471 m		2368 vw	3042
2363 m			2999
1721 vs	1698 s	1718 vs	1671	1721	1716	ν(C = O): COOH,
1622 vs	1620 vs	1618 vs	1653	1652	1613	C = O + δ_b(H₂O) + δ_def(N-H); NH₂
1557 s	1562 m	1531 s	1589	1581	1535	Ph breathing modes
1476 vs	1500 vs	1488 s	1503	1502	1491	CH; deformation of –CH₂-
1325 s	1392 w		1355	1389	1322
1319 s	1346 vs	δ_b(CH₂)	1309	1357	1263
1262 s	1262 vs	1263 s	1275	1283
1210 vw	ν(C-C)		1205
1169 vw	1160 w	1077 s	1161	1160	1136	(C-O) + ν(C-N) + ν(C-C) + ν_r(CH₂)
1089 w	1073 w	1028 w	1089	1093	1085
1026 mw	1030 m		1034	1039	1029
932 w	961 vw	929 s	932	962	926	CH-bend; phenyl
897 vw	939 vw	831 vw	899	939	859	δ_rock; ⁺NH₂
857 vw	895 m	819 vw	857	869	839
813 w	830 vw	805 vw	815	831	825
797 w	815 vw		793	802
	796 vw			791
749 ms	780 vw	722 vs	746	784	725	COO⁻))δ_b
702 s	746 vw		707	744
	702 ms			699
557 m	545 w	563 ms	558	548	570	Ring deformation
510 n	471 vw	521 ms	511	472	524	δ(ONO); PA
451 vw	431 w	466 vw	450	424	449	CNC deformation
		425 vw			417
ν, stretching; δ, bending ; ^a s = strong, w = weak, m = medium, sh = shoulder, v = very, br = broad;

Electronic absorption transitions and FMOs

Figure 3 displays an example of the determined spatial alignment of the frontier molecular orbitals (FMO) examination of the investigated (nor)(DNBA), (nor)(PA), and (cip)(PA) complexes. The HOMO orbitals of these complexes are only distributed over the extensive area of the donor molecules (nor and cip). The LUMO orbitals are only found on the acceptor molecules DNBA and PA. This outcome provides strong proof of the charge transfer process occurring from the donor part (mainly HOMO) to the acceptor part (mainly LUMO), leading to the formation of the CT complex [26].

Table 6 outlines calculated the energy levels of the HOMO and LUMO for the donors and acceptors, as well as the complexes formed in the gas phase using B3LYP/6-311G (d, p) method. The key electronic transition is from the HOMO orbital of the donor to the LUMO orbital of the acceptor, so increasing the HOMO energies of the donor molecules (cip and nor) and decreasing the LUMO energies of the acceptor molecules (PA and DNBA) should improve their interaction. This is because of the creation of a complex with a smaller band gap (∆E_g). In the gas phase, the ∆E_g values for the complexes of [(nor)(DNBA)], [(nor)(PA)], and [(cip)(PA)] are 2.849 eV, 3.198 eV, and 3.676 eV, respectively.

The energy values of the complex FMO levels are generally closer to the energy values of the FMO levels of the specific donor in that CT complex. Similarly, the energy values of the CT complex LUMO and HOMO levels are generally closer to the energy values of the LUMO and HOMO levels of the specific acceptor in that CT complex. This result matches well with the reported results and confirms the nature of the reaction that takes place between these two components [27]. For example, the HOMO energy of the [(cip)(PA)] complex (-6.69 eV) agrees well with the HOMO energy of cip (E_HOMO = -5.95 eV) and is significantly different from that of PA (E_HOMO = -8.41 eV). Correspondingly, the LUMO energy of the [(cip)(PA)] complex (− 3.02 eV) agrees well with the LUMO energy of cip (E_LUMO = -1.51 eV) and is significantly different from that of PA (E_LUMO = -4.05 eV). This observation could be generalized to all HOMO and LUMO levels of the CT complexes (see Table 6).

Table 6

Calculated energies of frontier molecular orbitals of free drugs (cip and nor), free–acceptors (PA, DNBA), and three complexes in the gas phase.
Compound	E_HOMO (eV)	E_LUMO (eV)	∆E_g (eV)
DNBA	-8.34	-3.55	4.97
nor	-5.88	-1.53	4.35
PA	-8.41	-4.05	4.36
cip	-5.95	-1.51	4.44
[(nor)(DNBA)]	-6.16	-3.31	2.85
[(nor)(PA)]	-6.38	-3.18	3.20
[(cip)(PA)]	-6.69	-3.02	3.68

Molecular electrostatic map (MEP)

Numerous articles have highlighted the simplicity of utilizing the molecular electrostatic potential (MEP), which combines total electron density with electrostatic potential (ESP) to show the relationship between the acceptor and donor molecules in CT complexes [28]. Figure 4 displays calculated maps for [(nor)(PA)], [(nor)(DNBA)], and [(cip)(PA)] complexes. A CT complex forms when there is an electrostatic interaction between two pairs with opposite charges, i.e. one with high density and one with low density [29]. In Fig. 4, red represents high electron density while blue represents low electron density; the electron density decreases in the order of orange, yellow, green, and blue. The MEP of these compounds indicates that there is a lack of electron density (green shade) spread out along the C = C bonds of the aromatic ring. The yellow color indicates the presence of high electron density, which is spread out across the edges of the molecule at the oxygen atoms. This outcome confirms the Mulliken charges present on these atoms. The electron density distribution aligns with the charges determined by Mulliken population analysis for each atom. The donor and acceptor interaction in the CT complex can be illustrated as electron resonance. This resonance occurs between two areas: one having a high electron concentration and the other with a low electron concentration.

The CT complexes attract the cip, nor, PA, and DNBA molecules to this area because of their low electron density. This is comparable to having a cavity filled. This confirms the CT process and shows that the alignment of the two parts was precise.

UV-Vis spectral analysis

To understand electronic transitions in these complexes better, calculations were done in the gas phase using the DFT/B3LYP method and 6-311G (d, p) basis set. Table 7 contains a summary of the absorption parameters, including wavelengths and oscillator strengths, that were calculated. As shown in Fig. 5, the absorption spectra of [(cip)(PA)], [(nor)(PA)], and [(nor)(DNBA)] complexes exhibit a peak absorption band at 380 nm, 387 nm, and 379 nm, respectively. Similar findings were noted for cip, nor, PA, and DNBA in the gas phase. All these species exhibit absorptions that can be measured between 239–334 nm (refer to Table 7). For example, the [(nor)(PA)] complex showed a new band at a higher wavelength of 387 nm, while the [(nor)(DNBA)] complex showed a new band at 379 nm. Therefore, the emergence of the new range of absorption bands (besides the color change) was regarded as proof of the electronic transition resulting from the creation of the complex. The 379 nm band in the [(nor)(DNBA)] complex represents a single electronic transition from the HOMO orbital (associated with nor) to the LUMO orbital (associated with DNBA). The molecular orbitals involved in transferring the other two complexes are the same as those in the [(nor)(DNBA)] complex.

Table 7

The calculated and experimental maximum absorption wavelengths (λ_max, nm) of free donors (cip and nor), free-acceptors (PA, DNBA), and complexes
Compound	Calculated	Experimental [11]	Oscillator Strength
DNBA	240	-	0.106
nor	242	-	0.097
PA	334	-	0.078
Cip	251	-	0.045
[(nor)(DNBA)]	379	297	0.2493
[(nor)(PA)]	387	300	0.1224
[(cip)(PA)]	380	278	0.1027

Electric moments

Table 8 provides the calculated electric moments, including dipole moments, mean polarizability, and first static hyperpolarizability, for the free donors, free acceptors, and complexes. The dipole moments of CT complexes typically vary from those of their individual donor and acceptor molecules. This outcome clearly shows the transfer of charge from the donor molecule to the acceptor molecule, as previously mentioned in reference [30]. For instance, the dipole moments of the unbound cip, nor, PA, and DNBA are 9.72, 10.23, 1.72, and 3.67 D, while the dipole moments of their respective CT complexes [(cip)(PA)], [(nor)(PA)], and [(nor)(DNBA)] are 12.80 D, 7.66 D, and 5.52 D, as shown in Table 8. This suggests that the difference in charge separation in the CT complex is higher than in the individual parts. Similarly, the donor having a greater dipole moment (more polar) creates a complex with a larger dipole moment as well. However, the acceptor that has a greater dipole moment does not necessarily create a complex with a greater dipole moment. This could validate the type of interaction between the electron-donor species (with a higher dipole moment) and the electron-acceptor species (with a lower dipole moment).

The growing use of electro-optic modulation, harmonic generation, frequency mixing, and higher data rates in communication technology requires research into finding materials with improved nonlinear optical (NLO) properties [31]. A review of the literature indicates that the energy gap between the LUMO and HOMO has an impact on the polarizability of a molecule. Molecules with small energy gap values exhibit significant linear polarizability. In our system under study, the highest linear polarizability value of 53.790×10^− 24 is exhibited by [(cip)(PA)], whereas the lowest linear polarizability value of 50.353×10^− 24 is observed in [(nor)(DNBA)]. The hierarchy of linear polarizability values [(cip)(PA)] > [(nor)(PA)] > [(nor)(DNBA)] is consistent with the energy gap order.

The first hyperpolarizability parameter was used to investigate NLO activity in great detail. A high first hyperpolarizability, β_total, suggests a favorable NLO material. In this research, the CT complexes exhibit notably high β_total values, falling within the range of 8.844×10^− 30 to 17.088×10^− 30 esu. Hence, these CT complexes are suitable options for NLO materials. The [(nor)(DNBA)] complex exhibits the highest total value, whereas the [(cip)(PA)] complex shows the lowest value (refer to Table 8). These CTCs exhibit β_total values that are multiple times higher than urea, a standard compound.

β_total = [(β_xxx + β_xyy + β_xzz)² + (β_yyy + β_yzz + β_yxx)² + (β_zzz + β_zyy + β_zxx)²]^1/2 (1)

Table 8

Calculated dipole moment (µ/Debye), average polarizability, and first-order hyperpolarizability in the gas phase of the free species and complexes
Compound	µ (D)	α_ave (a.u.)	α_ave (esu)	β_total (a.u.)	β_total (esu)
DNBA	3.67	108.474	16.076×10^− 24	54.030	0.467×10^− 30
nor	10.23	222.934	33.039×10^− 24	2814.511	24.320×10^− 30
PA	1.72	114.360	16.948×10^− 24	477.689	4.128×10^− 30
cip	9.72	229.048	33.945×10^− 24	1885.492	16.293×10^− 30
[(nor)(DNBA)]	5.52	339.762	50.353×10^− 24	1977.504	17.088×10^− 30
[(nor)(PA)]	7.66	349.713	51.827×10^− 24	1518.135	13.118×10^− 30
[(cip)(PA)]	12.80	362.957	53.790×10^− 24	1023.451	8.844×10^− 30
Urea	3.62	28.003	4.150 ×10^− 24	69.95	0.600×10^− 30
β: 1 atomic unit (a.u.) or Hartree = 8.641×10^− 33 cm⁵.esu^− 1= esu
α: 1 a.u. = 0.1482×10^− 24 esu

The study finds a good correspondence between calculated parameters and experimental data. The formation of CTCs is characterized by the transfer of electronic charge between molecules, stabilized by electrostatic attraction. Quantum mechanical computations, specifically DFT calculations, have been used to replicate and explain the experimental parameters of CTC formation. Also, shows evidence of charge transfer through changes in bond lengths and Mulliken electronic charges upon complex formation. Thermodynamic parameters, such as interaction energy, enthalpy, entropy, and Gibbs free energy, indicate that the complexes are stable and their formation is spontaneous and exothermic.

The IR analysis shows that the vibrational frequencies of the complexes are in agreement with experimental values, with shifts in IR bands attributed to the characteristics of the CT interaction. The electronic absorption transitions and frontier molecular orbitals (FMOs) analysis revealed that the HOMO orbitals are distributed over the donor molecules, while the LUMO orbitals are located on the acceptor molecules, confirming the charge transfer process.

The MEP analysis visualizes the electron density distribution and confirms the electrostatic interaction between the donor and acceptor molecules. The UV-vis spectral analysis shows new absorption bands for the complexes, indicating electronic transitions resulting from complex formation. The electric moments, including dipole moments, mean polarizability, and first static hyperpolarizability, demonstrate significant charge separation in the complexes, with the potential for nonlinear optical applications.This correspondence is important as it validates the computational methods used in the study and confirms the accuracy of the theoretical predictions regarding the molecular structures, electronic distribution, electric moments, and spectroscopic properties of the charge transfer complexes between norfloxacin/ciprofloxacin and picric acid/3,5-dinitrobenzoic acid. The agreement between theory and experiment provides confidence in the results and suggests that the DFT calculations can reliably model and explain the experimental observations for these systems.

Ethical Approval

This declaration is “not applicable”.

Competing interests

The authors declare they have no financial interests.

Authors contributions

Both authors have participated in (a) conception and design, or analysis and interpretation of the data; Dr. Rezvan has participated in drafting the article or revising it critically for important intellectual content; and (c) approval of the final version.

Funding

The authors have no financial or proprietary interests in any material discussed in this article.

Availability of data and materials

The data can be accessed by email ([email protected]) upon request from the corresponding author of the article, Dr. Hadigheh Rezvan.

F. Yakuphanoglu, M. Arslan, Opt. Mater. 27 (2004) 29.
S.M. Andrade, S.M.B. Costa, R. Pansu, J. Colloid Interf. Sci. 226 (2000) 260.
F. Yakuphanoglu, M. Arslan, Solid State Commun. 132 (2004) 229.
B. Chakraborty, A.S. Mukherjee, B.K. Seal, Spectrochim. Acta Part A 57 (2001) 223.
F. Yakuphanoglu, M. Arslan, M. Kucukislamoglu, M. Zengin, Sol. Energy 79 (2005) 96.
V. Hadigheh-Rezvan, DFT study of Molecular structure, and optical properties of charge transfer complexes derived from Tetrathiafulualene and Tetracyanoquinodimethane derivatives, J. Chem. Reactivity Synthesis, 2021 11, 1, 6–11
K. Ganesh, C. Balraj, A. Satheshkumar, K. P. Elango, Spectroscopic studies on the formation of charge transfer complexes of L-phenylalanine with 2,3, 5-trichloro-6-alkoxy-1,4-benzoquinones in aqueous medium, Arab. J. Chem. 12 (2019) 503–514. http://dx.doi.org/10.1016/j.arabjc.2014.10.020
A. F. M. Motiur Rahman, Ahmed H. Bakheit, S. Rahman, G.A. E. Mostafa, H. Alrabiah, Procainamide Charge Transfer Complexes with Chloranilic Acid and 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone: Experimental and Theoretical Study, Processes, 2023, 11, 711. https://doi.org/10.3390/pr11030711
T. Manna, S. Banerjee, S. Bhattacharya, Electronic structures of the electron donor-acceptor complexes of fullerenes C<background-color:#CCCCFF;usub>60</background-color:#CCCCFF;usub> and C<background-color:#CCCCFF;usub>70</background-color:#CCCCFF;usub> with azulene and some of its derivatives employing ab initio and DFT, Indian J. Chem., 94A, 1461(2010).
M. Shukla, N. Srivastava, S. Saha, Investigation of ground state charge transfer complex between paracetamol and p-chloranil through DFT and UV–visible studies, J. Mole. Struc., 1021, 15, 2012, 153–157. https://doi.org/10.1016/j.molstruc.2012.04.075
Refat MS, Elfalaky A, Elesh E., Spectroscopic and physical measurements on charge-transfer complexes: Interactions between norfloxacin and ciprofloxacin drugs with picric acid and 3, 5-dinitrobenzoic acid acceptors. J. mole. struc. 2011; 990 (1–3): 217–226. http://dx.doi.org/10.1016/j.molstruc.2011.01.049
M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G.A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H.P. Hratchian, A.F. Izmaylov, J. Bloino, G. Zheng, J.L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J.A. Montgomery Jr., J.E. Peralta, F. Ogliaro, M. Bearpark, J.J. Heyd, E. Brothers, K.N. Kudin, V.N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J.C. Burant, S.S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J.M. Millam, M. Klene, J.E. Knox, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, R.L. Martin, K. Morokuma, V.G. Zakrzewski, G.A. Voth, P. Salvador, J.J. Dannenberg, S. Dapprich, A.D. Daniels, Ö. Farkas, J.B. Foresman, J.V. Ortiz, J. Cioslowski and D.J. Fox, Gaussian 09, Revision D.01, Gaussian, Inc., Wallingford CT (2009).
A.D. Becke, Phys. Rev. A, 38, 3098 (1988).
B. Lee, W. Yang and R.G. Parr, Phys. Rev. B, 37, 785 (1988).
R. Dennington, T. Keith, and J. Millam, in ed.: S. Mission, Version 5, Semichem Inc., KS (2009).
Abdel Majid A. Adam1, Mahmoud Salman, T. Sharshar, Moamen S. Refat, Chemical, and Physical Studies on the Reaction Mechanism of Charge-Transfer Complexes Between Narcotic Drugs and Electronic Acceptors, Int. J. Electrochem. Sci., 8 (2013) 1274–1294
Haoyu Gong, Sicong Geng, Qi Zheng, Puxiu Wang, Lifeng Luo, Xiuzhi Wang, Yan Zhang, Yu Zhang, Haibing He, Xing Tang, An intravenous clarithromycin lipid emulsion with a high drug loading, h-bonding and a hydrogen-bonded ion pair complex exhibiting excellent antibacterial activity, Asian J. Pharmaceutical Sciences (2016) http://dx.doi.org/10.1016/j.ajps.2016.04.002.
Mulliken, R. S. (1955). "Electronic Population Analysis on LCAO-MO Molecular Wave Functions. I". The J. Chem. Physics. 23 (10): 1833–1840. http://dx.doi.org/10.1063/1.1740588.
G. Briegleb, J. Czekalla, Z. Physikchem. (Frankfurt) 24 (1960) 237.
Rahman, A.F.M.M.; Bakheit, A.H.; Rahman, S.; Mostafa, G.A.E.; Alrabiah, H. Procainamide Charge Transfer Complexes with Chloranilic Acid and 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone: Experimental and Theoretical Study. Processes 2023, 11, 711. http://dx.doi.org/10.3390/pr11030711
Pankin, D.; Smirnov, M.; Roginskii, E.; Savin, A.; Kolesnikov, I.; Povolotckaia, A. Density Functional Study of Structural and Vibrational Properties of _β-Moganite. Photonics 2023, 10, 1346. http://dx.doi.org/10.3390/photonics10121346
D.A. Skoog, Principle of Instrumental Analysis, third ed., Saunders College Publishing, New York, USA, 1985 (Chap. 7).
Hamza El Hadki, Mohammed Salah, Abdallah Zrineh, Khadija Marakchi, Hassna AbouEl Makarim, Najia Komiha, Oum Keltoum Kabbaj, Spectral characteristics and DFT Study of vanadyl octaethylporphyrin complex, Mediterranean J. Chem. 2019, 8(2), 132–139. DOI: http://dx.doi.org/10.13171/mjc8219043008heh
G.V. Girichev, N.I. Giricheva, O.I. Koifman, Y.V. Minenkov, A.E. Pogonin, A.S. Semeikind, S.A. Shlykov, Molecular structure and bonding in octamethylporphyrintin(II), SnN4C28H28, Dalton Trans., 2012, 41, 7550–7558.
L.J. Bellamy, The Infrared Spectra of Complex Molecules, Chapman & Hall, London, 1975.
A.Zrineh., K.Bahja.M., Ferhat., J.M. Barbe, R. Guilard; Metal elements present in black phosphate minerals of Youssoufia (Morocco), characterization of vanadyl and nickel porphyrins, Analysis, 1995, 23(5), 222–22
Selvam, L.; Vasilyev, V.; Wang, F. Methylation of zebularine: a quantum mechanical study incorporating interactive 3D PDF graphs. J. Phys. Chem. B 2009, in press.
G. Aloisi, S. Pignataro, J. Chem. Soc. Faraday Trans. 69 (1972) 534.
Van Leeuwen, R.; Baerends, E.J. Exchange-correlation potential with correct asymptotic behavior. Phys. Rev. A 1994, 49, 2421.
E.M. Breitung, C.-F. Shu, R.J. McMahon, Thiazole and thiophene analogs of donor-acceptor stilbenes: molecular hyperpolarizabilities and structure-property relationships, J. Am. Chem. Soc. 122(6) (2000) 1154–1160.
G. Smith, R.C. Bott, A.D. Rae, A.C. Willis, Aust. J. Chem. 53 (2000) 531.

No competing interests reported.

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DFT Study of Charge Transfer Complexes Between Norfloxacin and Ciprofloxacin Drugs with Picric Acid and 3,5-Dinitrobenzoic Acid Acceptors

Status:

Version 1

Abstract

Figures

Introduction

Computational method

Results and discussion

Optimized geometries

Mulliken electronic charge

Thermodynamic parameters

IR analysis

Electronic absorption transitions and FMOs

Molecular electrostatic map (MEP)

UV-Vis spectral analysis

Electric moments

Conclusion

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1