Molecular structure-associated pharmacodynamic investigation on benzoyl peroxide using spectroscopic and quantum computational tools

ABSTRACT

The pharmacodynamic activity on the organic structure of benzoyl peroxide has been analysed by molecular spectroscopical tools (IR, Raman, nuclear magnetic resonance and UV–visible). Simultaneously, the results obtained in the experimental process are verified by performing Quantum Gaussian computational calculations with higher-order basis sets. The actual positions of internal compositions and purity of the compound are verified with the observations of fundamental and group frequency of the recorded pattern of the FT-IR and FT-Raman spectra. The chemical environment of different carbons existing in various entities for approving a drug property is keenly identified and distinguished. The energy level degeneracy among different Frontier molecular orbitals is viewed from the orbital overlapping interaction contour. The biological activity of the present compound is emphasized and correlated with the hyperpolarizability profile of the internal coordinate system of a molecular structure arrangement. The involvement of non-bonding molecular orbital for the inducement of drug reactivity is monitored from the observation of cluster electron transitions. The Gibbs energy for chemical reaction with augmented temperature is relatively discussed, and the continuum of chemical reaction is observed.

KEYWORDS:

• Benzoyl peroxide
• non-bonding molecular orbital
• orbital overlapping interaction
• Gibbs energy
• cluster electron transitions

1. Introduction

Benzoyl peroxide [(C₆H₅CO)₂O₂] (BP) is an organic compound belonging to the peroxide family and it consists of two benzyl rings which are coupled by a peroxide group. It is a colourless crystalline solid and its melting point lies between 104°C and 106°C, and it will explode when its boiling point is at 107°C. It is easily soluble in alcohol, ether and water and its solubility value is 9.1 mg/lit at 25°C in water. BP is widely used as an initiator and catalyst in the food preservative industry [1]. BP is a vital therapeutic agent for acne vulgaris due to its in vitro antimicrobial activity against Propionibacterium acnes [2]. Owing to the use of topical and systemic antibiotics for acne vulgaris, the incidence of antibiotic-resistant Propionibacterium acnes is increasing worldwide.

The efficacy of BPO can be enhanced when used in combination with topical retinoids, antibiotics and tertiary amines. It contains combinations that induce effective bacterial resistance and that are important in bacterial infections’ treatment for moderate to heavy acne vulgaris. Of late, BPO has been commonly used as a topical drug for the treatment of acne vulgaris worldwide [3–4]. In addition to that, BP also has antimicrobial activity against P. acnes and moreover possesses keratolytic/comedolytic and anti-inflammatory effects [5]. BP data compiled from recent research [6,7] indicate that it is a safe drug.

In spite of its important antibiotic and anti-inflammatory applications, BP has not been subjected to systematic investigation on the structure activity associated with its pharmaceutical potential. Therefore, the present investigation was conducted for the strong interpretation of the structure activity connected with the inducement of active drug property of the compound using spectroscopic data and computational results.

2. Experimental profile

Physical state

• The prepared compound is in the solid phase and is found to be pure and of spectroscopic grade.

Recording profile

• The FT-IR and FT-Raman spectra of the compound were recorded using a Bruker IFS 66V spectrometer and the instrument adopted with an FRA 106 Raman module equipped with aNd : doped yttrium aluminum garnet laser source operating at 1.064 µm line widths with 200 mW power [8]. A standard optical system was used with KBr windows for data collection over a spectral range of 8300–350 cm⁻¹ at the best resolution of 0.5 cm⁻¹. Which is standard, high-performance, room-temperature LiTaO₃ (lithium tantalate) MIR detector with an signal to noise ratio of 9300 : 1.

• The high-resolution hydrogen nuclear magnetic resonance (¹HNMR) and carbon nuclear magnetic resonance (¹³CNMR) spectra were recorded using the 300 MHz and 75 MHz FT-NMR spectrometer [9]. The instrument was provided with Standard 5 mm nuclear magnetic resonance (NMR) tubes and less than 1.0 Hz (20 ppb) at full width at half maximum.

• The UV–visible spectrum was recorded in the range of 200 to 800 nm, with the scanning interval of 0.2 nm, using the UV-1700 series instrument [10].

3. Computational profile

In order to design the structure precisely, calculate geometrical parameters, display the Mulliken charge levels, study the vibrational spectral properties, observe the molecular orbital interactions, examine the frontier molecular transitions on the electronic structure, the entire quantum chemical computations were performed using the Gaussian 09 D. 01.version software program in a core i7 computer [11]. The computational calculations were performed over all the geometrical parameters, vibrational frequencies, simulation of molecular structure and spectra using B3LYP and B3PW91 methods adopted with 6–31++G(d, p) and 6-311++G(d,p) basis sets.

Particularly, for aromatic polyatomic complex molecules, the density functional theory (DFT) methods lead the prediction for finding more accurate molecular structure and vibrational frequencies. In DFT methods, Becke’s three-parameter hybrids’ function combined with the Lee–Yang–Parr correlation function (B3LYP) precisely gives good molecular structures, vibrational frequencies and charge densities in strongly bounded systems. Becke’s three-parameter exact exchange function (B3) combined with the gradient-corrected correlational function of Lee, Yang and Parr (LYP) and Perdew and Wang (PW91) predicts the best results for molecular geometry and vibrational wave numbers for a moderately larger molecule.

The optimized molecular structure is presented in three different forms in Figure 1. The energy absorbance by the present compound related with electronic spectra and the non bonding orbital (NBO) calculation are performed by using the NBO 6.1 program and HOMO–LUMO high occupied molecular orbitals (HOMO)–low unoccupied molecular orbitals (LUMO) depletion energies were calculated using the time-dependent self consistent field method with the best fit basis set. In the same way, the ¹H and ¹³C NMR chemical shifts with respect to tri methyl saline (TMS) were calculated by the gauge independent atomic orbital method using the integral equation formalism variant polarizable continuum model in combination with B3LYP/6-311++G(2d,p). The Mullikan charge assignment on different parts of the compound was calculated and was purposely elucidated for the determination of the key factor for pharmaceutical activity of the compound. The dipole moment, linear polarizability and the first-order hyper polarizability in different coordinates of the compound were computed using the B3LYP method with the 6-311++G(d,p) basis set. The electronic circular dichroism and vibrational circular dichroism (VCD) spectra were simulated from available frequencies, the optical chirality was studied and the mechanism for masking the toxicity was interpreted.

Figure 1. The optimized molecular structure of benzoyl peroxide.

4. Results and discussion

4.1. Structural property and molecular geometry deformation analysis

The molecular properties of the present compound have been studied by the calculated specific absorption rate parameters, obtained using HyperChem 8.0.6 software which is depicted in Table 1. Topological polar surface area of the compound is a significant parameter which is used to predict the ability of drug transport properties. This factor is basically associated with the rate of human intestinal membrane penetration and the Caco-2 monolayer’s permeability. Here, the parameter value was found to be 52.60 A², due to which it possessed enhanced intestinal absorption. If the molecular mass is less than 500 Da, it will be able to pass through the cell membrane. Here, the value was identified to be 242.05 g/mol, which is half of the limit and was permeable with the cell membrane. The present molecule has H-bond donor and acceptor count 0 and 4, respectively, and consequently the present drug conformed to Lipinski's rule and success to display drug likeness.

Table 1. Physical parameters of benzoyl peroxide.

Parameters	Values
Hydrogen bond donor count	0
Hydrogen bond acceptor count	4
Rotatable bond count	5
Topological polar surface area	52.6 A^2
Mono isotopic mass	242.058 g/mol
Exact mass	242.058 g/mol
Heavy atom count	18
Covalently bonded unit count	1

The molecular deformation view is shown in Figure 2 and the present molecule possesses bi-symmetry by which it belongs to the C_2V point group symmetry. The optimized geometrical parameters have been presented in Table 2. The two phenyl rings are connected with one another by peroxide groups. In order to equal the existing electrochemical moment, both the benzene rings are placed perpendicular to each other with respect to the ligand groups. Normally, the migration of electrons from the bonds makes the covalent to coordinate with the covalent bond. This effect induces some peculiar chemical property in the compound [12]. Here, after attaining the optimized molecular structure, the covalent bond between O₁ and O₂ is observed to be coordinate covalent bond. Such a change in the compound is the root cause of inducement of effective bacterial resistance in the compound. At the centre, two phenyl rings are conjugated by the symmetrical ligand groups of C=O–O and thus two carbonyls strongly coupled with two benzene rings. In the left moiety, the bond lengths C6–C8 and C6–C10 are stretched by 0.009 Å than C8–C12 and C10–C14. Simultaneously, the bond lengths C12–C16 and C14–C16 are stretched by 0.005 Å than the others in the right moiety of the ring.

Figure 2. Molecular structure in the Cartesian coordinate system.

Table 2. Optimized geometrical parameters for benzoyl peroxide (BPO) computed at HF/DFT (B3LYP&B3PW91) with 6-31++G(d,p) and 6-311++G(d, p) basis sets.

Geometrical parameters	Methods
	HF	B3LYP		B3PW91
	6-311+G (d, p)	6-31++G (d, p)	6-311++G (d, p)	6-311+G (d, p)
Bond length (Å)
O1–2O	1.359	1.4173	1.4276	1.4131
O1–C17	1.3562	1.383	1.3897	1.3807
O2–C18	1.3562	1.383	1.3897	1.3807
O3–C17	1.1737	1.2028	1.1965	1.1944
O4–C18	1.1737	1.2028	1.1965	1.1944
C5–C7	1.3896	1.4005	1.4	1.3945
C5–C9	1.3898	1.4014	1.4008	1.3954
C5–C17	1.4876	1.485	1.4877	1.4831
C6–C8	1.3896	1.4005	1.400	1.3945
C6–C10	1.3898	1.4014	1.4008	1.3954
C6–C18	1.4875	1.485	1.4876	1.4831
C7–C11	1.3822	1.3911	1.39	1.3852
C7–H19	1.0735	1.0854	1.0828	1.0835
C8–C12	1.3822	1.3911	1.3901	1.3852
C8–H20	1.0735	1.0854	1.0828	1.0835
C9–C13	1.384	1.3925	1.3914	1.3867
C9–H21	1.0727	1.0844	1.0818	1.0825
C10–C14	1.384	1.3925	1.3914	1.3867
C10–H22	1.0727	1.0844	1.0818	1.0825
C11–C15	1.3867	1.3964	1.3951	1.3904
C11–H23	1.0748	1.0861	1.0838	1.0842
C12–C16	1.3867	1.3964	1.3951	1.3904
C12–H24	1.0748	1.0861	1.0838	1.0842
C13–C15	1.3855	1.3958	1.3946	1.3897
C13–H25	1.0748	1.0861	1.0838	1.0842
C14–C16	1.3855	1.3958	1.3944	1.3897
C14–H26	1.0748	1.0861	1.0838	1.0842
C15–H27	1.0756	1.0865	1.0843	1.0847
C16–H28	1.0756	1.0865	1.0843	1.0847
Bond angle (°)
O2–O1–C17	112.527	110.9056	111.3155	110.9182
O1–O2–C18	112.5328	110.9056	111.3024	110.9182
C7–C5–C9	120.1467	120.1098	119.9958	120.0512
C7–C5–C17	117.208	116.8944	117.003	116.8783
C9–C5–C17	122.645	122.9943	122.9995	123.0685
C8–C6–C10	120.1471	120.1098	119.9955	120.0512
C8–C6–C18	117.2091	116.8944	117.0035	116.8783
C10–C6–C18	122.6435	122.9943	122.9993	123.0685
C5–C7–C11	119.9596	119.9148	119.971	119.9674
C5–C7–H19	119.2063	118.8173	118.9077	118.7388
C11–C7–H19	120.8341	121.2678	121.1212	121.2937
C6–C8–C12	119.9595	119.9148	119.9688	119.9674
C6–C8–H20	119.2063	118.8173	118.9092	118.7388
C12–C8–H20	120.8342	121.2678	121.1219	121.2937
C5–C9–C13	119.7069	119.645	119.7038	119.686
C5–C9–H21	120.2684	120.1338	120.0911	120.1275
C13–C9–H21	120.024	120.2193	120.2034	120.184
C6–C10–C14	119.7064	119.645	119.7038	119.686
C6–C10–H22	120.2683	120.1338	120.0908	120.1275
C14–C10–H22	120.0247	120.2193	120.2037	120.184
C7–C11–C15	119.8527	119.9914	120.0013	119.9644
C7–C11–H23	119.9413	119.8367	119.8525	119.8787
C15–C11–H23	120.2059	120.1718	120.1461	120.1568
C8–C12–C16	119.8529	119.9914	119.9987	119.9644
C8–C12–H24	119.9413	119.8367	119.8532	119.8787
C16–C12–H24	120.2057	120.1718	120.1479	120.1568
C9–C13–C15	120.0459	120.1904	120.1989	120.1741
C9–C13–H25	119.7775	119.698	119.7083	119.73
Dihedral angles (°)
C17–O1–O2–C18	89.6954	88.4662	88.3928	−88.0502
O2–O–C17–O3	−1.5807	−0.5275	−0.9525	0.3776
O2–O1–C17–C5	177.9108	178.7867	178.4381	−178.9187
O1–O2–C18–O4	−1.591	−0.5275	−0.9549	0.3776
O1–O2–C18–C6	177.9091	178.7867	178.4403	−178.9187
C9–C5–C7–C11	−0.1899	−0.3081	−0.2926	0.3191
C9–C5–C7–H19	179.7568	179.6063	179.6156	−179.563
C17–C5–C7–C11	−179.99	−179.8875	−179.8351	179.8333
C17–C5–C7–H19	−0.0434	0.0269	0.0732	−0.0487
C7–C5–C9–C13	0.1107	0.1477	0.1214	−0.1188
C7–C5–C9–H21	−179.6012	−179.3454	−179.3999	179.3066
C17–C5–C9–C13	179.8996	179.7004	179.6353	−179.6017
C17–C5–C9–H21	0.1877	0.2073	0.114	−0.1764
C7–C5–C17–O1	−176.9834	−173.6794	−173.9123	172.7191
C7–C5–C17–O3	2.4883	5.609	5.4524	−6.5516
C9–C5–C17–O1	3.2219	6.7544	6.5602	−7.7826
C9–C5–C17–O3	−177.3064	−173.9572	−174.0751	172.9466
C10–C6–C8–C12	−0.191	−0.3081	−0.2903	0.3191
C10–C6–C8–H20	179.7544	179.6063	179.6192	−179.563
C18–C6–C8–C12	−179.9882	−179.8875	−179.8378	179.8333
C18–C6–C8–H20	−0.0428	0.0269	0.0717	−0.0487
C8–C6–C10–C14	0.1108	0.1477	0.122	−0.1188
C8–C6–C10–H22	−179.6014	−179.3454	−179.4024	179.3066
C18–C6–C10–C14	179.8966	179.7004	179.6412	−179.6017
C18–C6–C10–H22	0.1844	0.2073	0.1168	−0.1764
C8–C6–C18–O2	−176.9738	−173.6794	−173.9732	172.7191
C8–C6–C18–O4	2.5068	5.609	5.3964	−6.5516
C10–C6–C18–O2	3.2345	6.7544	6.4941	−7.7826
C10–C6–C18–O4	−177.2849	−173.9572	−174.1363	172.9466
C5–C7–C11–C15	0.1334	0.2322	0.2378	−0.2547
C5–C7–C11–H23	−179.9648	−179.9097	−179.9013	179.8875
H19–C7–C11,C15	−179.8123	−179.6801	−179.6684	179.6242
H19–C7–C11–H23	0.0894	0.178	0.1926	−0.2335
C6–C8–C12–C16	0.1352	0.2322	0.2344	−0.2547
C6–C8–C12–H24	−179.9655	−179.9097	−179.9029	179.8875
H20–C8–C12–C16	−179.8094	−179.6801	−179.6731	179.6242
H20–8–C12–H24	0.09	0.178	0.1897	−0.2335
C5–C9–C13–C15	0.0242	0.0879	0.104	−0.145
C5–C9–C13–2H5	−179.8609	−179.76	−179.7568	179.7163
H21–C9–C13–C15	179.7367	179.5806	179.6248	−179.57
H21–C9–C13–H25	−0.1483	−0.2673	−0.236	0.2913
C6–C10–C14–C16	0.0244	0.0879	0.1016	−0.145
C6–C10–C14–H26	−179.8621	−179.76	−179.7588	179.7163
H22–C10–C14–C16	179.7373	179.5806	179.6255	−179.57
H22–C10–C14–H26	−0.1492	−0.2673	−0.235	0.2913

Similarly, in the second ring, the bond lengths C5–C9 and C7–C5 are 0.009 Å greater than C11–C7 and C9–C13 of the left moiety and the bond lengths C13–C15 and C11–C15 are 0.004 Å greater than C7–C11 of the right moiety. Here, the substitutional groups are peroxide ligand, due to the insertion of the groups in both the benzene rings, the hexagonal frame is found to be little contravention. The reception of the peroxide groups is evidenced from the semicircular distortion in the rings. The bond length of C5–C17 and C6–C18 are 0.087 Å greater than carbon carbon (CC) of the ring. The bond lengths of the peroxide groups are consistently same since the ligand groups are highly symmetrical. Due to the injection of substitutions, the bond angles C9–C5–C7 and C8–C6–C10 are squeezed by 0.29° since both the rings pulled away from the substitutions. Thus, the bond length and bond angle changes in the compound, emphasizing that the exchange of electron clouds between the rings via peroxide groups causes the drug property in the compound.

4.2. Mulliken charge distribution

The charge distribution among the molecular orbitals described the energy transitions for generating the desired molecular properties such as physical as well as chemical properties. The consumption of energy during the vibrations showed the orientation of electron potential in different parts of the compound. Normally, the electron cloud is oriented on the side of the peroxide group since it contains four oxygens. Here, the electron clouds are directly concentrated over the carbons of the benzene rings and are directed from the peroxide groups via the peroxide-connected carbon of the top moiety of the ring to create the wonderful drug property for the title compound. Due to the orientation, the carbons of the peroxide groups become neutral, whereas the electron cloud remains concentrated on π-bonded 3O and 4O in order to maintain the chemical equilibrium. In addition to that, strong dipole bonds (C=O) are created symmetrically on the peroxide groups. The negative charge distribution appears on both sides of the molecule and the depletion zone is centred at the peroxide group due to which the strong drug property is consistently emphasized. The protonic content is richer in one of the carbons of both benzene rings than the others since the electronic charges oscillate back and forth with respect to the peroxide group. This form of asymmetric charge orientation causes the anti-inflammatory application. The asymmetric is charge a separation in the present compound is clearly shown in Figure 3.

Figure 3. The asymmetric Mulliken charge separation of benzoyl peroxide.

4.3. Vibrational assignments

The fundamental group frequencies of organic complex: benzoyl peroxide has been assigned according to its characteristic vibrational regions with a high degree of accuracy. Since the entire molecule belongs to multiple planes due to the different breaking regions, the point group is supposed to change from C_2V to C_S. Due to this the molecule belongs to the C_S point group symmetry which contains 28 atoms in different planes; so it has 78 normal vibrational modes. Out of that, the fundamental vibrations of the present molecule are distributed as 53 in-plane vibrations denoted by A′ species and 25 out-of-plane vibrations denoted by A″ species, i.e. Γ_vib = 53A′ + 25A″. The observed FT-IR and FT-Raman frequencies and calculated fundamentals have been presented in Table 2. Comparing the calculated frequencies with the experimental values showed the over-estimation of the calculated vibrational modes due to the violation of the state of the real system. Inclusion of electron correlation in the DFT makes the frequency values smaller in comparison with the Hartree Fock (HF) calculated data. The vibrational pattern generated by the FT-IR and FT-Raman spectrometer is presented in Figures 4 and 5, respectively (Table 3).

Figure 4. FT-IR vibrational spectral pattern of benzoyl peroxide.

Figure 5. The FT-Raman spectra of benzoyl peroxide.

Table 3. Observed and HF and DFT (B3LYP & B3PW91) with 6-31++G(d,p) and 6-311++G (d,p) level calculated vibrational frequencies of benzoyl peroxide (BPO).

S. no	Symmetry species CS	Observed frequency (cm^−1)		Methods				Vibrational Assignments
				HF	B3LYP		B3PW91
		FT-IR	FT-Raman	6-311++G (d,p)	6-31++G (d,p)	6-311++G (d,p)	6-31++G (d,p)
1	A^′	−	3090vs	3068	3006	3001	2993	(C–H) υ
2	A^′	−	3080vs	3068	3006	3001	2993	(C–H) υ
3	A^′	−	3070vs	3062	3000	2993	2986	(C–H) υ
4	A^′	−	3060vs	3062	3000	2993	2986	(C–H) υ
5	A^′	3050w	−	3044	2986	2980	2986	(C–H) υ
6	A^′	−	3040vw	3044	2986	2980	2975	(C–H) υ
7	A^′	−	3010vw	3034	2978	2972	2967	(C–H) υ
8	A^′	−	2980w	2844	2978	2972	2967	(C–H) υ
9	A^′	−	2940w	2831	2966	2959	2956	(C–H) υ
10	A^′	−	2900w	2954	2966	2959	2956	(C–H) υ
11	A^′	1790s	−	1728	1713	1717	1718	(C=O)υ
12	A^′	1770vs		1703	1581	1565	1697	(C=O)υ
13	A^′	1600vs	1600m	1522	1536	1533	1435	(C=C)υ
14	A^′	1590m	−	1522	1535	1533	1538	(C=C)υ
15	A^′	1490w	1490w	1503	1419	1399	1418	(C=C)υ
16	A^′	1445s	1445w	1503	1419	1399	1418	(C=C)υ
17	A^′	1400w	−	1404	1423	1422	1422	(C=C)υ
18	A^′	1380w	−	1403	1423	1422	1422	(C=C)υ
19	A^′	1370w	−	1360	1383	1383	1382	(C–C)υ
20	A^′	1320m	1320w	1359	1292	1277	1289	(C–C)υ
21	A^′	1280w	1280w	1243	1271	1265	1268	(C–C)υ
22	A^′	1230vs	1230vs	1242	1270	1265	1268	(C–C)υ
23	A^′	1220vs	1220vs	1205	1254	1252	1251	(C–C)υ
24	A^′	−	1190m	1158	1171	1154	1250	(C–C)υ
25	A^′	1180m	1180m	1138	1168	1164	1173	(C–O)υ
26	A^′		1165m	1137	1159	1156	1165	(C–O)υ
27	A^′	−	1150w	1104	1122	1124	1118	(C–C)υ
28	A^′	1100w	−	1096	1119	1121	1115	(C–C)υ
29	A^′	1070w	−	1091	1105	1108	1101	(C–H) δ
30	A^′	1030m	−	1036	1033	1107	1027	(C–H) δ
31	A^′	1005s	−	1035	1036	1037	1035	(C–H) δ
32	A^′	1000vs	1000vs	999	1034	1035	1032	(C–H) δ
33	A^′	−	950w	996	925	985	930	(C–H) δ
34	A^′	940w	940vw	976	919	908	919	(C–H) δ
35	A^′	895vw	895s	857	910	895	913	(C–H) δ
36	A^′	−	890vs	857	888	878	893	(C–H) δ
37	A^′	−	885vs	857	884	878	886	(C–H) δ
38	A^′	840m	840m	849	883	873	884	(C–H) δ
39	A^′	−	800m	849	733	737	738	(O–O) υ
40	A^″	795m	−	846	731	733	738	(C–H) γ
41	A^″	705s	−	699	721	728	726	(C–H) γ
42	A^″	700s	700vs	695	721	728	726	(C–H) γ
43	A^″	−	695w	692	692	699	709	(C–H) γ
44	A^″	−	690w	685	691	698	700	(C–H) γ
45	A^″	−	660m	685	681	685	545	(C–H) γ
46	A^″	−	650w	620	624	629	2344	(C–H) γ
47	A^″	−	620vs	615	624	629	2338	(C–H) γ
48	A^″	610vw	−	611	618	624	2338	(C–H) γ
49	A^″	510w	−	491	493	492	491	(C–H) γ
50	A^′	500vw	−	463	526	521	528	(C=O) δ
51	A^′	−	475w	460	461	463	460	(C=O) δ
52	A^′	470w	−	409	465	459	465	(CCC) δ
53	A^′	460w	−	406	464	458	464	(CCC) δ
54	A^′	−	450vw	391	460	454	459	(CCC) δ
55	A^′	−	440vw	386	456	448	457	(CCC) δ
56	A^′	−	400vw	386	398	399	357	(CCC) δ
57	A^′	−	360vw	379	390	391	348	(CCC) δ
58	A^′	−	365vw	346	363	363	321	(C–O) δ
59	A^′	345m	−	346	363	363	321	(C–O) δ
60	A^′	340w	−	355	329	324	330	(C–C) δ
61	A^′	330w	−	318	332	335	339	(C–C) δ
62	A^″	320w	−	316	326	330	331	(CCC)γ
63	A^″	300w	−	314	292	286	289	(CCC)γ
64	A^″	290m	290m	289	298	300	299	(CCC)γ
65	A^″	250vw	−	232	270	264	266	(CCC)γ
66	A^″	240w	−	227	233	232	231	(CCC)γ
67	A^″	220w	−	202	224	221	226	(CCC)γ
68	A^′	200m	−	197	196	195	196	(O–O) δ
69	A^″	190v	190m	192	178	198	179	(C=O) γ
70	A^″	−	170m	168	179	179	181	(C=O) γ
71	A^″	−	160w	158	156	156	155	(C–O) γ
72	A^″	155w	−	151	237	234	1	(C–O) γ
73	A^″	100w	−	107	115	93	94	(O–O) γ
74	A^″	95w	−	130	115	113	91	(C–C) γ
75	A^′	−	85w	64	65	60	73	(C=O–O) δ
76	A^″	−	55w	51	38	49	59	(C–C) γ
77	A^″	−	40w	41	38	36	59	(C=O–O) γ
78	A^″	−	30w	33	36	35	25	Ring τ

Scaling factors: HF-0.923, 0.985, 0.866; B3LYP/6-31-0.853, 0.908, 0.890; B3LYP/6-311-0.852, 0.907, 0.898; B3PW91-0.865, 0.822, 0.950, 0.845.

VS – very strong; S – strong; m – medium; w – weak; as – asymmetric; s – symmetric; υ – stretching; α – deformation, δ – in plane bending; γ – out plane bending; τ – twisting.

In order to compensate for deficient energy calculations on the tail end of an excited state and the loosely bonded electrons, computational scientists usually use diffuse functions. One needs to include diffuse functions (functions with small exponents, hence large radial extent) to predict properties of anions accurately. Diffuse functions are also necessary to describe certain non-bonding interactions. These basis sets utilize very small exponents to clarify the properties of the tail. Differences between diffuse basis sets are mostly due to the differences in their core and not in their diffuse component.

4.3.1. C–H vibrations

In all organic ring compounds, the purposive insertion of ligand groups for attaining desired drug properties was always pronounced in the fundamental modes of ring vibrations. Here, the peroxide ligand only the substitutional group which is acting as symmetrical bridge and link two benzene rings. With the symmetrical linking of benzene rings with peroxide groups, both the rings are twisted perpendicular to each other. The impact of injection of the substitutional group can be identified by the rate of suppression of vibrational modes of ring vibrations. Here, due to the mono substitution, 10 C–H bonds were identified and proportionate stretching vibrations were possible and consequently 20 bending vibrations will be observed continuously. In general, the C–H stretching vibrations are observed in the region 3000–3100 cm⁻¹ for benzene derivatives [13–15]. Accordingly, in this case, the C–H stretching peaks were available with very strong to very weak intensity at 3090, 3070, 3060, 3050, 3040, 3010, 2980, 2940 and 2900 cm⁻¹. Except one, all the bands are found in Raman spectrum which contradicts previous works [16]. Here, it is found that, except three peaks, all the vibrational bands are observed within the expected region which showed the lesser impact was pronounced on the ring vibrations due to the substitutions. Apart from that, three infected bands inferred that such bonds are placed beside the substitutional groups.

Here, the C–H in-plane bending modes are found at 1070, 1030, 1005, 1000, 950, 940, 895, 890, 885 and 840 cm⁻¹. The out-of-plane bending is observed at 795, 705, 700, 695, 690, 660, 650, 620, 610 and 510 cm⁻¹. Regularly, two different vibrational bending bands were identified in the region 1300–1000 cm⁻¹ and 1000–750 cm⁻¹, respectively [17–19]. The part of in-plane bending modes is pulled well below the expected region whereas, except one, all the out-of-plane vibrations are moved down to the lower end of the expected region. Unlike stretching, the bending modes have much influence since the adoption of the ligand group. The entire ring C–H vibrations have suffered much. This view clearly described that the energy of ring modes are utilized by the ligand vibrations which leads to the inducement of a new property of the compound.

4.3.2. CC vibrations

Generally, the phenyl core CC (C=C and C–C) stretching vibrations are observed in the region 1600–1400 cm⁻¹ [20–22], in which the frequencies in the region 1600–1500 cm⁻¹ are fundamentally assigned to C=C stretching and the rest to C–C stretching conservatively. In those bonds, since C=C and C–C bonds are unpredictable within the ring, three bonds of each of two rings are to be assigned and proportionately three stretchings of each bond are possible. Therefore, the C=C and C–C stretching bands are found at 1600, 1590, 1490, 1445, 1400 and 1380 cm⁻¹ and 1370, 1320, 1280, 1230 and 1220 cm⁻¹, respectively. Due to the strong bonding of the ligand with the core directly, the ring stretched diagonally. Except one band related to C=C, all stretchings are significantly found well below the expected region whereas the entire C–C stretching modes moved away from the characteristic region of the spectra. This appearance indicated that most of the potential energies are exchanged between rings via ligand for the enhancement of drug property of the compound. The ring carbon carbon carbon (CCC) in in-plane and out-of-plane breathing has been found at 470, 460, 450, 440, 400 and 360 cm⁻¹ and 320, 300, 290, 250, 240 and 220 cm⁻¹, respectively. Even a single ring breathing mode has not been identified within the limit of the expected region. From this condition, it is concluded that, due to the strong binding of the ligand group, the ring might not be breathing well.

4.3.3. Peroxide group vibrations

All acid peroxides have a weak absorption band in the region 900–800 cm⁻¹ [13,23] due to the O–O stretching vibration. Acid peroxides also have two strong bands at 1820–1810 cm⁻¹ and 1800–1780 cm⁻¹ (saturated aliphatic) due to their C=O stretching vibration. Usually, the intensity of those bands is very high. For aryl and α, β-unsaturated acid peroxides, these bands occur at 1805–1780 cm⁻¹ and 1785–1755 cm⁻¹. The nature and position of the substituent(s) in the aromatic portion of acid peroxides may significantly influence the position of these bands. Here, the O–O stretching vibration is found with medium intensity at 800 cm⁻¹. Its corresponding in-plane and out-of-plane bending bands are found at 200 and 100 cm⁻¹, respectively. The band is located at the tail end of the expected region which is mainly due to uncertainty of the bond and high homo nuclear character. The C=O is the major part of the peroxide group and its stretching vibrations are observed at 1790 and 1770 cm⁻¹ in the IR spectrum. These modes are −20 cm⁻¹ dislocated from the expected region which demonstrates their involvement in transformation of electronic potential for generating the desired property. The C=O in-plane and out-of-plane bending modes appeared at 500 and 475 cm⁻¹ and 190 and 170 cm⁻¹, respectively. The C–O stretching vibrations are found in the region 1300–1050 cm⁻¹ which are not very useful in the characterization of acid peroxides. The C–O stretching peaks appeared at 1180 and 1165 cm⁻¹ which are positioned in the middle part of the spectrum, emphasizing its domination over the O–O bond in order to hold the ring proximity. The C–O in-plane and out-of-plane bending modes were identified at 365 and 345 cm⁻¹ and 160 and 155 cm⁻¹, respectively.

4.4. NMR assessment

The observed and simulated ¹³C and ¹H NMR spectra of the BP compound are presented in Figure 6 and their results are depicted in Table 4. The ¹³C spectral is significantly vital in order to identify the chemical pattern of biochemically important molecules [24]. In this compound, the carbon is situated in three different atmospheres in which the complete pattern is observed. Here, the carbons presented in base as well as substitutional groups and are differentiated with respect to their positions. The calculated chemical shift of C5 and C6 are 142 ppm whereas the observed shift is found to be 134 and 135 ppm. The calculated shift is more than observed values since their phases differ. The chemical shift of adjacent carbons C7 and C8 is 165 ppm and it is observed to be more than other carbons in the ring which is mainly due to asymmetrical breaking of the proton shield. It is also noted that C7 and C8 are more deshielded since the energy exchange is taking place between rings via the ligand through these carbons.

Figure 6. The observed and simulated ¹³C and ¹H NMR spectra of benzoyl peroxide.

Table 4. Experimental and calculated ¹H and ¹³C NMR chemical shifts (ppm) of benzoyl peroxide (BPO).

Atom position	TMS-B3LYP/6-311++G(2d,p) Shift (ppm)			Experimental shift (ppm)
	Gas	Solvent phase
		DMSO	CCl4
C5	140.56	142.08	142.61	134
C6	140.56	142.08	142.61	135
C7	146.69	143.32	146.74	165
C8	146.69	143.32	146.74	165
C9	137.46	137.95	138.35	128
C10	137.46	137.95	138.35	128
C11	140.50	140.82	140.34	141
C12	140.50	140.82	140.34	141
C13	141.81	142.08	141.20	143
C14	141.81	142.08	141.20	143
C15	146.74	147.21	145.77	152
C16	146.74	147.21	145.77	152
C17	207.42	194.33	193.11	180
C18	207.42	194.33	193.11	182
H19	8.744	8.849	8.817	−
H20	8.744	8.849	8.817	−
H21	7.999	7.973	7.955	7.4
H22	7.999	7.973	7.955	7.4
H23	7.892	7.973	7.872	7.4
H24	7.892	7.973	7.872	7.4
H25	7.795	7.855	7.725	7.4
H26	7.795	7.855	7.725	7.4
H27	7.973	8.081	7.914	7.4
H28	7.973	8.081	7.914	−

Note: DMSO, dimethyl sulfoxide.

The calculated and observed chemical shifts of carbons C17 and C18 are found to be 193 ppm and 180 and 182 ppm, respectively. The chemical shifts of these carbons (C17 and C18) are greater than other carbons present in the molecule due to the asymmetrical breaking of the paramagnetic shield. This is obviously observed due to the holding the peroxide group and also bridge point of exchange of electron clouds between rings. The chemical shift of the remaining carbons in the ring ranges from 128 to 152 ppm, which fluctuate with a huge difference of values du to the arbitrary movement of electron clouds with large potential. This view emphasized the process of making compound be drug. Similar to the carbons in the ring, the chemical shift of H in the rings fluctuated from 7.9 to –8.8 ppm. The abrupt transformation of energy via the core carbons also affects the chemical shift of ring hydrogens in the ring.

4.5. Frontier molecular interaction examination

The formation of molecular orbitals from the atomic orbital is recognized by two sets of orbitals HOMO and LUMO in which the energy of the molecular orbitals was rearranged from a higher value to a lower energy value [25]. Usually, the maximum energy value is found to be prearranged from the first HOMO to the last LUMO level. The chemical energy value of the compound is directly proportional to the energy value difference between HOMO and LUMO [26], and the potential energy was exchanged to produce the desirable chemical behaviour.

The Frontier molecular orbital (FMO) interaction is shown in Figure 7. Here, the Lewis base; (electron-pair donor) HOMO appears over semicircle of core CC bonds of benzene entities. Here, the orbital electrons are shared their orbital lobes and it is possible to donate the electron clouds to produce the chemical energy for the process of drug property. In the carbonyl group, the π-interaction flavour becomes visible. Simultaneously, the positive and negative iso surfaces are found to be reversed in the high molecular orbital (HMO-1) level which showed the reverse orbital interaction coupling. In Lewis acid (electron acceptor); LUMO, the π and σ-orbital interaction orbitals appeared in the ring and peroxide group, respectively. The σ-orbital interaction process takes place around the C of the ring and C of the peroxide group and O of the same groups. In LUMO+1, the intensity of σ-orbital interaction increases and the cascade process is extended with some more orbitals. Thus the two rings are connected with peroxide groups by transformation of electron cloud through σ and π interaction lobes and besides the chemical property is mixed and new drug property is produced.

Figure 7. The FMO interaction profile of benzoyl peroxide.

4.6. UV–visible absorption analysis

The electronic excitation parameters are presented in Table 5 and the FMO levels of IR and UV–visible regions are depicted in Table 6. The CT complex absorption spectra of the compound are important to know the details of exchange of electronic energy between two significant entities (donor and acceptor) for occurring chemical reaction to generate desired chemical properties. The CT complex transfer spectra also directly describe that part of the compound that cause the formation of new physical as well as chemical properties [27,28]. Usually, the charge transfer progression takes place between base ligand groups in the chemical compound since the ligand groups are the major source of formation of the needed chemical property.

Table 5. Theoretical electronic absorption spectra of benzoyl peroxide (BPO) (absorption wavelength λ (nm), excitation energies E (eV) and oscillator strengths (f)) using the TD-DFT/CAM B3LYP/6-311++G(d,p) method.

λ (nm)	E (eV)	(f)	Transition level	Major contribution	Assignment	Region	Bands
Gas
287.93	4.305	0.095		H → L (92%)	n → π*	Quartz UV	R-band (German, radikalartig)
286.96	4.320	0.015	H–L, H–L+1	H → L (89%)	n → π*
271.60	4.565	0.476		H → L−1 (86%)	n → π*
DMSO
288.12	4.304	0.104	H–1–L, H–L	H → L (90%)	n → π*	Quartz UV	R-band (German, radikalartig)
287.22	4.319	0.018		H → L+1 (90%)	n → π*
271.16	4.560	0.522		H → L+1 (87%)	n → π*	Quartz UV
CCl4
282.07	4.391	0.032		H → L (86%)	n → π*	Quartz UV	R-band (German, radikalartig)
282.12	4.395	0.089	H–L, H–L+1, H–1–L	H → L+1 (85%)	n → π*
269.23	4.605	0.557		H−1 → L (78%)	n → π*

Table 6. Frontier molecular orbitals of benzoyl peroxide (BPO) with energy levels.

Energy levels	Frequency region B3LYP/6-311++G(d,p) (eV)	UV–visible region (eV)
H+10	−10.3634	−10.1299
H+9	−10.0034	−10.0290
H+8	−9.9863	−9.9229
H+7	−9.2755	−9.8722
H+6	−9.2186	−8.5441
H+5	−8.3375	−8.4551
H+4	−8.1985	−8.2113
H+3	−7.6099	−7.6668
H+2	−7.5985	−7.6306
H+1	−7.5367	−7.5065
H	−7.5353	−7.4942
L	1.9317	2.4952
L-1	1.8661	2.4427
L-2	0.8710	1.0653
L-3	0.8658	1.0615
L-4	0.5964	0.2484
L-5	0.2862	0.2359
L-6	0.2005	0.0149
L-7	0.2400	0.1112
L-8	0.2514	0.2898
L-9	0.3278	0.3134
L-10	0.6160	0.4359

Here, the benzene rings act as base compound and peroxide groups act as ligand groups. Necessarily, the CT transformation takes place between them and is directly evidenced from Mulliken charge levels. Here, the transition is represented by n → π* and observed at 271 nm on the energy gap of 4.565 eV with oscillator strength of 0.478. This absorption band is designated by 92% of H-L level and such a band (R-band-German, radikalartig) is assigned to the UV region of the spectrum. In the solvent phase (DMSO and CCl₄), the same band was found at 271 and 269 nm on the energy gap of 4.56 and 4.60 eV with oscillator strength of 0.52 and 0.55, respectively. According to Figure 7, there are several molecular orbitals overlapping that appeared between the ligand and base rings and the observed transition is found to be very strong and emphasized the energy exchange between peroxide groups to benzene rings from side to side. Usually, if the CT band is identified in Quartz-UV, the compound will be drug active [29]. Here, a similar drug property is observed in this compound; in addition to that, the charge transfer is restricted within the closed path between rings via the peroxide group for deducing consistent drug action.

4.7. Molecular electrostatic potential (MEP) maps

Usually, after the formation of the chemical compound by fusing the base with ligand groups, the chemical charges are enforced to organize in order to equalize the induced dipoles. Thereby, two opposite extremely charged regions (protonic and electronic) are alienated with respect to the rate of chemical-potential energy which is utilized for displacing electron clouds. The depleted MEP appearance on various parts of the molecule is shown in Figure 8.

Figure 8. The MEP diagram of benzoyl peroxide.

The source of rich protonic region is represented by a rich green shade whereas the origin of the enriched electronic region is designated by the red region of the colour spectrum. In this case, the protonic region is symbolized over hydrocarbons around both benzene rings by a high degree of green shadow and is shielded by the positive charges rigidly. The electronic clouds are concentrated in the mid region of the molecule (red region) which divides the positive boundary symmetrically. The charge depletion zone is found with a yellow colour region which lies between the red and green regions. Two dipoles are observed between the green and red regions of the molecule altogether which seems to indicate that the protons are bundled by an electron rope. From this view, it can be concluded that the strong electrophilic-nucleophilic dipole is established between rings and peroxide groups. This colour structure of the molecule is able to maintain the drug consistency and this system of the molecule acted as a good receptor ligand for the concerned protein absorption.

The potential envelope grid points are internally connected and the corresponding iso surface clearly appears as in Figure 9. In the figure, the potential field is found to be spread out from the peroxide group and core of benzene rings aggressively. Normally, the potential field starts from the main group of the molecule which causes the generation of a peculiar drug property. Accordingly, in this case, the peroxide group linked with symmetrical benzene rings is the root cause of biological activeness.

Figure 9. ESP view of benzoyl peroxide.

4.8. Physico-chemical properties

The chemical properties related to molecular structure and Frontier molecular energy levels of the present compound are computed and the entire parameters are presented in Table 7.

Table 7. Calculated energies, chemical hardness, electro negativity, chemical potential, electrophilicity index of benzoyl peroxide (BPO) in the UV–visible region.

Parameter	B3LYP 6311++G (d,p)	UV–visible	Electrophilicity charge transfer (ECT) (ΔNmax)A − (ΔNmax)B
Etotal (kcal/mol)	−840.25	−840.34
EHOMO (eV)	7.596	7.494
ELUMO (eV)	1.930	2.495
ΔEHOMO−LUMO gap (eV)	5.666	4.999
EHOMO−1 (eV)	7.597	7.506	+ 2.21(eV)
ELUMO+1 (eV)	1.859	2.495
ΔEHOMO−1−LUMO+1 gap (eV)	5.737	5.011
Chemical hardness (η) (eV)	2.833	2.499
Electronegativity (χ) (eV)	4.763	4.994
Chemical potential (μ) (eV)	4.763	4.994
Chemical softness (S) (eV)	−11.33	−9.998
Electrophilicity index (ω) (eV)	4.004	4.990
Dipole moment (Dyne)	1.191	4.940

The zero point vibrational energy of the compound is found to be −840.25 K cal/mol and is same in both the IR and UV–visible regions. This circumstance shows the wide range of chemical consistency. The resultant dipole moment of the molecule as a whole is the gauge of asymmetric charge displacement and the same is found to be 1.19 and 4.94 dyne in the IR and UV–visible region, respectively. The actual dipole moment is greater in the UV–visible region than the IR region which shows the rich biological activity in UV–visible boundary. In this case, the base compound is a couple of benzenes; its dipole moment is almost zero whereas when peroxide groups are substituted between two rings, the total computed dipole moment is found to be very high and it is stressed that the asymmetric charge orientation reflected the desired pharmaceutical property.

Chemical hardness is one of the highly useful concepts which enable chemists to understand reactivities of a chemical compound. The chemical stability of the aromatic chemical species is normally determined from generated molecular orbitals’ (HOMO and LUMO) energy gap. In this case, it is found to be 2.83 and 2.49 eV in the IR and UV–visible regions, respectively. If the measured value of the molecule is greater than unity, the compound will be chemically strong and it will be having good reactivity. Here, the observed values showed reasonable chemical stability and it is also much reactive in the Quartz UV region.

The electron affinity of the molecule is very vital for finding whether the reaction is exothermic or endothermic [30,31] and measured reaction ability is found to be 4.7 and 4.9 in the IR and UV–visible region. The observed value showed the reaction is exothermic and a prominent amount of energy is released during the reaction.

The ionization potential energy is one of the primary energy considerations used in quantifying chemical bonds and characterizes the electron’s bond strength [32]. The direction and cause of polarity of the molecule can be identified strongly. The ionization potential is observed to be 1.93 and 2.49 which is moderate and it is adequate to maintain the chemical bond stability. Electronegativity is a measure of the ability of an atom in a molecule to draw bonding electrons to itself. An important application of electronegativity is in the prediction of the polarity of a chemical bond [33]. Here, both parameters were found to be 4.76 and 4.99 in the IR and UV region, respectively. The observed values are so high and demonstrate the fine reactive nature and its structure form leads the dual bonds between two benzene rings and peroxide group and is strongly evidenced in the MEP diagram.

The electrophilicity index is a gauge of rate of potential energy flow through generated interactive molecular orbitals. Here, the electrophilicity index is 4.00 and 4.99 eV in the IR and UV–visible region correspondingly. But, it is found to be 2.09 eV for the benzene ring. The resultant energy is considerably very high which shows a huge amount of energy flow through overlapped orbitals which is due to the symmetrical existence of the benzene rings about the peroxide group. The energy transformation is clearly evidenced from the electrophilicity charge transfer of the compound which is found to be +2.21. From this observation, it is inferred that such large amount of energy is needed to induce the antibiotics activity.

4.9. Polarization and hyperpolarization analysis

The chemical polarization index of the organic compound represents the molecular orbital arrangement in different internal coordinate systems. The hyper polarizability indicates the occurrence of a hyper interaction of complex molecular orbitals for inducing drug activity. The higher-order methods of computed polarizability and first-order hyperpolarizability indices are depicted in Table 8. The calculated dipole moment showed that the axis of molecular groups of the compound belongs to the z coordinate which is ensured by the high value of dipole moment on the same coordinate system. The calculated average polarizability and anisotropy of the polarizability is 270 × 10⁻³⁰ and 353 × 10⁻³⁰ esu, respectively. This is comparatively so high which is mainly due to strong coupling of benzenes with the peroxide group. The hyperpolarizability β is one of the imperative key systems which designate hyper interaction of molecular orbitals. Normally, the hyper interaction is very intensive in a drug complex. Here, the calculated first hyperpolarizability value (β) is 353.99 × 10⁻³³ esu. From this observation, it is clear that the hyper asymmetrical polarization appears irrespective of base and substitutional groups which strappingly authorize the particular pharmaceutical property.

Table 8. The dipole moments µ (D), the polarizability α (a.u.), the average polarizability α_o (esu), the anisotropy of the polarizability Δα (esu) and the first hyperpolarizability β(esu) of benzoyl peroxide (BPO).

Parameter	Values	Parameter	Values
αxx	−65.090	βxxx	0.0076
αxy	−2.629	βxxy	−0.0102
αyy	−103.88	βxyy	−0.0195
αxz	−0.0009	βyyy	−0.0043
αyz	−0.0019	βxxz	−15.96
αzz	−104.60	βxyz	−32.56
αtot	270.65	βyyz	8.467
Δα	353.99	βxzz	0.0248
μx	0.0007	βyzz	0.0039
μy	0.0001	βzzz	1.0929
μz	1.1914	βtot	353.994
μ	1.19

4.10. Thermodynamical functions analysis

Normally, the thermodynamic analysis on an aromatic compound is very important since it provides the necessary information regarding the chemical reactivity [34]. The thermodynamic functional parameters are depicted in Table 9. The variation of thermodynamic functional parameters with temperature is shown in Table 8. The calculated entropy, specific heat capacity and enthalpy were found to be varied with a positive temperature coefficient. When the temperature increased from 100 K to absolute temperature 298.15, the functional parameters were varied unhurriedly whereas from 350 to 1000 K, the thermodynamic functions seemed to swing in a linear pattern and were rather constant at maximum temperature. This view of variation showed the consistent chemical reactivity and considerable chemical hardness of the present compound. The Gibbs free energy is always a negative temperature coefficient and here since it was found to be true, the present compound has strong and unique chemical property and endless chemical reaction.

Table 9. Specific heat capacity, entropy and enthalpy at different temperatures for benzoyl peroxide (BPO).

T (K)				Gibbs free energy KJ mol^−1
100.00	143.0	118.20	4.12	−11815.9
200.00	224.47	142.87	8.09	−28565.9
298.15	377.14	214.28	25.61	−63862
300.00	427.22	269.86	50.32	−80907.7
400.00	518.65	298.32	50.85	−119277
500.00	613.42	372.21	83.91	−186021
600.00	723.18	443.82	124.44	−266168
700.00	829.24	505.04	171.52	−353356
800.00	924.32	568.72	224.13	−454752
900.00	1018.15	603.58	281.41	−542941
1000.00	1090.45	678.10	342.64	−677757

The entropy is a measure of disorder of the chemical system with respect to temperature. It reflects the unavailable energy to do the chemical reaction. In this case, it is observed to be increased according to the temperature randomly which illustrates the consistency of the chemical reaction for the inducement of drug property. The enthalpy is the measurement of the energy transformation of the system externally or internally [35]. The ΔH is a positive change in endothermic reactions, and negative in heat-releasing exothermic processes. In this case, the reaction magnitude is found to be positive and the chemical reaction is endothermic which describes the considerable energy is utilized for fusing peroxide group with phenyl rings. The specific heat capacity of the present compound also increased with respect to temperature. The kinetic energy of the atoms or molecules is increased across the chemical system boundary. From this condition, it is clear that the confined drug system is formed and the kinetics of internal parts of molecule is active. Gibbs free energy is a thermodynamic potential of thermodynamic chemical system that can be used to calculate the maximum of reversible work [36]. In this case, the observed values for various temperatures are negative which means that the chemical reactivity is irreversible and permanent.

4.11. NBO transition analysis

The hybridization of molecular orbitals is classified into bonding and anti-bonding orbitals which describes the transformation of internal energy by electron transitions. Usually, the electron density is delocalized from occupied Lewis type (bond or lone pair (LP)) orbitals and unoccupied (anti-bonding and Rydberg) non-Lewis orbital in order to stabilize donor-acceptor interaction [37–41]. The donor and acceptors of electronic orbitals are identified and their energy transitions are presented in Table 10.

Table 10. The calculated NBO of benzoyl peroxide by second-order perturbation theory.

Donor (i)	Type of bond	Occupancy	Acceptor (j)	Type of bond	E2 kcal/mol	Ej – Ei au	F(I j) au
O1–O2	σ	1.98422	C17	σ*	0.53	2.89	0.035
O1–O2	σ		C18	LP	0.53	2.89	0.035
O3–C17	π	1.99301	C5	LP	1.28	2.58	0.051
O4–C18	π	1.99301	C6	π*	1.28	2.58	0.051
C5–C17	σ	1.97928	O1	LP	0.53	2.98	0.036
C5–C17	π		O1	LP	0.53	2.98	0.036
C6–C18	σ	1.97928	O2	LP	0.53	2.98	0.036
C7–C11	σ	1.97976	C15–H27	LP	1.00	4.51	0.060
C8–C12	σ	1.97976	C16–H28	LP	1.26	4.18	0.065
C11–C15	π	1.98739	C15–H27	LP	1.15	4.67	0.066
C11–C15	π		C15–H27	LP	0.96	4.04	0.058
C12–C16	π	1.98739	C15–H27	LP	1.64	4.67	0.078
O2	LP	1.99974	C18	LP	1.06	21.81	0.136
O1	LP	1.97553	C17	LP	1.06	21.81	0.136
O1	LP		O1–O2	σ*	0.52	20.98	0.094
O1	LP		O2–C18	σ*	0.54	20.99	0.097
C14–C16	σ	0.01652	C15–H2	LP	1.16	4.50	0.065
O1	LP	1.97553	C17	LP	1.36	21.52	0.153
O2	LP	1.99974	C18	LP	1.35	21.57	0.153
O2	LP		O1–O2	σ*	0.52	20.98	0.094
O3	LP	0.00911	O1–C17	σ*	0.54	20.99	0.097
O3	LP		C17	LP	5.28	21.34	0.301
O3	LP		O3–C17	π*	1.01	20.48	0.135
O3	LP		O4–C18	π*	0.56	20.48	0.100
O3	LP		C5–C17	σ*	0.50	20.96	0.093
O4	LP	0.00911	C18	LP	5.26	21.39	0.301
O4	LP		O3–C17	π*	0.56	20.48	0.100
O4	LP	0.00911	O4–C18	π*	1.01	20.48	0.135
O4	LP		C6–C18	σ*	0.50	20.95	0.093
C5	LP	0.00826	C7	LP	0.53	12.53	0.073
C5	LP		C7	LP	2.40	12.09	0.152
C5	LP		C9	LP	0.87	12.05	0.091
C5	LP		C17	LP	1.15	12.44	0.107
C5	LP		O1–C17	σ*	0.73	11.62	0.084
C5	LP		O3–C17	π*	0.56	11.92	0.073
C5	LP		C5–C7	π*	1.44	12.04	0.118
C5	LP		C7–C11	σ*	0.69	11.78	0.081
C5	LP		C7–H19	σ*	0.61	11.92	0.076
C6	LP	0.00826	C8	LP	0.53	12.53	0.073
C6	LP		C8	LP	2.40	12.09	0.152
C6	LP		C10	LP	0.87	12.05	0.091
C6	LP		C18	LP	1.15	12.44	0.107
C6	LP		O2–C18	σ*	0.73	11.62	0.084
C6	LP		O4–C18	π*	0.56	11.92	0.073
C6	LP		C6–C8	π*	1.44	12.04	0.118
C6	LP		C8–C12	σ*	0.69	11.78	0.081
C6	LP		C8–H20	σ*	0.61	11.92	0.076
C7	LP	0.00640	C5	LP	1.41	12.44	0.118
C7	LP		C5	LP	1.98	12.37	0.140
C7	LP		C11	LP	0.93	12.02	0.094
C7	LP		H19	LP	0.67	12.03	0.080
C7	LP		C5–C7	σ*	1.35	12.02	0.114
C7	LP		C5–C9	σ*	1.09	11.76	0.102
C7	LP		C5–C17	π*	1.01	11.75	0.098
C8	LP	0.00640	C6	LP	1.41	12.44	0.118
C8	LP		C6	LP	1.98	12.37	0.140
C8	LP		C12	LP	0.93	12.02	0.094
C8	LP		H20	LP	0.67	12.03	0.080
C8	LP		C6–C8	π*	1.35	12.02	0.114
C8	LP	0.00640	C6–C10	σ*	1.09	11.76	0.102
C8	LP		C6–C18	π*	1.01	11.75	0.098
C9	LP	0.00577	C5	LP	1.14	12.37	0.106
C9	LP		C13	LP	0.80	12.51	0.089
C9	LP		C13	LP	2.52	12.03	0.155
C9	LP		H21	LP	0.59	11.98	0.075
C9	LP		C5–C7	π*	0.55	12.02	0.073
C9	LP		C9–C13	π*	1.11	12.02	0.104
C9	LP		C13–C15	σ*	0.86	11.76	0.090
C9	LP		C13–H25	σ*	0.61	11.89	0.076
C10	LP	0.00577	C6	LP	1.14	12.37	0.106
C10	LP		C14	LP	0.80	12.51	0.089
C10	LP		C14	LP	2.52	12.03	0.155
C10	LP		H22	LP	0.59	11.98	0.075
C10	LP		C6–C8	π*	0.55	12.02	0.073
C10	LP		C10–C14	π*	1.11	12.02	0.104
C10	LP		C14–C16	π*	0.86	11.76	0.090
C10	LP		C14–H26	σ*	0.61	11.89	0.076
C11	LP	0.00599	C7	LP	0.75	12.07	0.085
C11	LP		C15	LP	0.84	12.50	0.091
C11	LP		C15	LP	2.50	12.01	0.155
C11	LP		H23	LP	0.64	11.98	0.078
C11	LP		C11–C15	π*	1.19	12.01	0.107
C11	LP		C13–C15	σ*	0.84	11.76	0.089
C11	LP		C15–H27	σ*	0.50	14.80	0.077
C12	LP	0.00599	C8	LP	0.75	12.07	0.085
C12	LP		C16	LP	0.83	12.50	0.091
C12	LP		C16	LP	2.49	12.01	0.154
C12	LP		H24	LP	0.64	11.98	0.078
C12	LP		C12–C16	π*	1.19	12.01	0.107
C12	LP		C14–C16	σ*	0.84	11.76	0.089
C13	LP	0.00622	C9	LP	0.70	12.50	0.084
C13	LP	0.00622	C9	LP	2.37	12.03	0.151
C13	LP		C15	LP	0.90	12.01	0.093
C13	LP		H25	LP	0.62	11.98	0.077
C13	LP		C5–C9	σ*	0.89	11.76	0.092
C13	LP		C9–C13	π*	1.16	12.02	0.105
C13	LP		C9–H21	π*	0.63	11.90	0.077
C14	LP	0.00622	C10	LP	0.70	12.50	0.084
C14	LP		C10	LP	2.37	12.03	0.151
C14	LP		C16	LP	0.90	12.01	0.093
C14	LP		H26	LP	0.62	11.98	0.077
C14	LP		C6–C10	σ*	0.89	11.76	0.092
C14	LP		C10–C14	π*	1.16	12.02	0.105
C14	LP		C10–H22	σ*	0.63	11.90	0.077
C15	LP	0.00621	C11	LP	0.77	12.51	0.088
C15	LP		C11	LP	2.48	12.02	0.154
C15	LP		C13	LP	0.84	12.03	0.090
C15	LP		H27	LP	0.64	11.98	0.078
C15	LP		C7–C11	σ*	0.82	11.76	0.088
C15	LP		C11–C15	π*	1.16	12.02	0.105
C15	LP		C11–H23	σ*	0.63	11.89	0.078
C16	LP	0.00621	C12	LP	0.77	12.51	0.088
C16	LP		C12	LP	2.48	12.02	0.154
C16	LP		C14	LP	0.84	12.03	0.090
C16	LP		H28	LP	0.66	11.97	0.079
C16	LP		C8–C12	σ*	0.82	11.76	0.088
C16	LP		C12–C16	π*	1.16	12.02	0.105
C16	LP		C12–H24	σ*	0.63	11.89	0.078
C17	LP	0.01785	C5	LP	1.11	12.61	0.106
C17	LP		O1–C17	σ*	1.64	11.77	0.127
C17	LP		C5–C9	σ*	0.57	11.94	0.074
C18	LP	0.01785	C6	LP	1.11	12.61	0.106
C18	LP		O2–C18	σ*	1.64	11.77	0.127
C18	LP	0.01785	C6–C10	σ*	0.57	11.94	0.074
O1	LP	1.97553	O2	LP	0.71	2.50	0.038
O1	LP		C17	LP	0.52	2.51	0.032
O1	LP		O2	LP	0.59	2.68	0.036
O1	LP		C17	LP	1.38	2.72	0.056
O2	LP	1.99974	O1	LP	0.71	2.50	0.038
O2	LP		C18	LP	0.52	2.51	0.032
O2	LP		O1	LP	0.59	2.68	0.036
O2	LP		C18	LP	1.38	2.72	0.056
O3	LP	0.00911	C17	LP	3.22	3.01	0.091
O3	LP		C15–H27	σ*	0.70	4.17	0.050
O4	LP	0.00911	C18	LP	3.22	3.01	0.091

In the peroxide group, the transition occurs from O1–O2 to C17 and C18 and it is assigned to σ–σ* by which 0.53 kcal/mol energy is transferred in order to connect the C and O, whereas the transition occurs from O3–C17 and O4–C18 to C5 and C6 and it is assigned π–π* interaction for which 1.28 kcal/mol energy is observed. The important transition is observed from peroxide O to C15, C16, C18, C5 and C6 with the energy gap of 21.81 a.u.; such amount of energy is absorbed from external energy for creating the desired chemical property. This transferred energy is further conducted through the ring for inducing drug property by the transitions (σ–σ* and π–π*) from C5 and C6 to C5–C7, C7–H18, C12, C6–C8, C6–C10, C9–C13 with 1.01 kcal/mol with energy gap of 12.50 a.u. The same transition (LP – σ* and π*) occurs from C12 and C13 to C8, C16, C12–C16, C14–C16, C9, C15 by intake of energy 2.37 kcal/mol. by crossing the energy gap of 11.98 a.u. The important transitions of σ–σ* (SP-hybridization) and π – π* (SP²-hybridization) are identified from C5–C17 and C6–C18 to O1 and O2 and also C5–C9, C5–C7, C6–C10, C6–C8, C8–C12 and so on, by back and forth oscillations of chemical kinetics in order to stimulate successful antibiotic activity. Though the lower order energies are observed for producing transitions, the electron clouds are crossed considerable energy gap for attaining enriched internal drug energy.

4.12. VCD verification

The VCD verification of the compound is mainly used for stereochemical examination; it is sensitive to the absolute configuration as well as to conformational features, which are often completely obscured in the ordinary absorption spectrum. It is greatly mapped to analyse some critical aspects regarding the interpretation of electronic CD spectra of organic compounds. The vibrational circular dichroism is the difference between the absorption of left and right circularly polarized lights through which the identity can be checked abruptly. The identity is used to elucidate the characteristics of chromophores causing the rate of drug purity and toxicity. The VCD spectrum of the present molecule is depicted in Figure 10 in which strong transmission and absorption peaks are obtained in various regions. Some peaks with same intensity are identified in the chromophores region (1700–1550 cm⁻¹) which clearly indicate the greatest purity and less toxicity of the present compound. The hindering of fingerprint peaks in the higher wavenumber region showed the unavailable involvement of ring vibrations in the toxic effect of the molecule.

Figure 10. VCD spectrum of benzoyl peroxide.

5. Conclusion

The compound BP is the primary derivative of benzene. In order to predict the unknown chemical properties, different analyses have been made on the chemical structure. The molecular deformation analysis gave the complete information regarding the amendment of benzene structure for fixing the peroxide group to generate physical fitness for drug activity. The chemical charge equilibrium between bonded entities exposed the asymmetric movement of the charges which is favourable for inducement of a peculiar drug property. The vibrational pattern assignments of the molecular complex explicit the fundamental IR and Raman frequencies which are uniquely stressed the correct compositional bonds which self-possessed the compound. The chemical reaction path arrangement of different carbons is ensured from the discrete chemical shift and the fundamental cause is drawn. The orbital interaction lobe formation favoured the chemical process to produce a desirable drug property was predicted from the cascade arrangement of molecular orbital boundary. The chromophores reactivity on the base compound causing the electronic shift in UV–visible spectra is argued in detail. The CT band of electronic transitions between ligand and base compound is evaluated and the presence of the band in the appropriate region of the spectrum causing the drug property is determined.

Acknowledgements

The authors thank the computational consultancy, Department of Physics, A.V.C. College (Autonomous), Mayiladuthurai, Tamilnadu, India, for providing computational Lab facility to carry out the computational calculations.

Disclosure statement

No potential conflict of interest was reported by the authors.