Biological systems depend on solar radiation for energy to sustain life. Unfortunately, chronic exposure to solar ultraviolet radiation (UVR) is responsible for health problems such as premature aging, erythema, skin cancers and sunburn      . Melanin (naturally occurring UV-absorbing pigment in the human skin) provides the first line of defense to the harmful effects of UVR but does not provide enough shield against high levels of UVR. To this effect, organic sunscreens are frequently used as photoprotectors  . Recently, attention has been shifted towards the use of sunscreens which in addition to the screening of detrimental UVR equally have photoprotection constituents  . Antioxidants efficiently serve this purpose, since they scavenge UV-induced free radicals   . Flavonoids, polyphenols, resveratrol, etc., have been explored for such purposes. To qualify as a potential organic molecule for sunscreen applications, the molecule must be able to block UVR and scavenge resultant free radicals from UVR exposure   . Knowledge of sunscreens comprising UV filters and antioxidant ingredients serve as a novel photoprotective strategy and research in this field is ongoing     .
2-(2’-hydroxy-5’-methylphenyl)-benzotriazole (PBT) commonly known as drometrizole (see Figure 1) is considered as a sunscreen ingredient and is utilized as a UV absorber and stabilizer    . Furthermore, it is known to
Figure 1. Schematic representation of PBT and its ortho-substituted derivatives with atomic numbering scheme (ED and EW represent electron-donating and attracting groups).
have antioxidant and stabilizing effects and has been approved as an indirect food additive  . Reference  reported that PBT is a potent Exited state intramolecular proton transfer (ESIPT)-mediated Non-linear optical (NLO) molecular switch which could be used as a chromophore. Despite all the studies on drometrizole from literature, there is no comprehensive theoretical study on the structure-antioxidant relationship as well as the antioxidant mechanism of drometrizole. Additionally, the presence of some substituents on PBT may enhance its antioxidant properties. Interestingly, electron-donating groups (EDGs) and electron-withdrawing groups (EWGs) are known to significantly affect the antioxidant activity of a phenolic antioxidant  . This insight has been a prime aid for the design and synthesis of new and more effective antioxidants  . Three major mechanisms to scavenge free radical by antioxidants have been recognized   . These include hydrogen atom transfer (HAT), single-electron transfer followed by proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET). The antioxidant activity of the phenolic antioxidants can be assessed thermodynamically by several physicochemical parameters such as O-H bond dissociation enthalpy (O-HBDE), proton dissociation enthalpy (PDE), proton affinity (PA), ionization potential (IP) and electron transfer enthalpy (ETE).
As can be seen in Figure 1, the structural features of drometrizole (pi-conjugation, presence of hydroxyl group) and its above-mentioned properties warrant it to be a potent antioxidant-UV filter. Such a study is conveniently achieved via the use of density functional theory (DFT) and time-dependent DFT (TD-DFT) methods. DFT has been utilized by several authors to predict the relationship between the structure-activity of a compound and also for the design of novel potential antioxidants  .
Within the framework of the design of more UV filter-antioxidant-based molecules, this work had as the main objective, to evaluate the thermodynamics of the antioxidant mechanism and UV-absorption properties of PBT using the DFT and TD-DFT methods. In addition, the effects of an electron-donating substituent (EDS) and an electron-accepting substituent (EAS) (see Figure 1) on the antioxidant activity and UV spectra of PBT were assessed. The effects of these substituents were explored with the intention of improving their anti-oxidant efficiencies. A comprehension of why a mechanism is favored over another requires in due course some kinetic studies to confirm speculations drawn from thermodynamic studies. However, this is not the main aim of this study. Here, we set out to specifically: 1) Find drometrizole derivatives with high antioxidant activity from a theoretical point of view; 2) Identify the substituent that are the most effective in reducing the BDE, IP, and PA; 3) Find the preferred mechanisms in the gas and solvent phases from a thermodynamic perspective; 4) Compute the UV spectra of these molecules. To achieve these, the physiochemical descriptors including O-HBDE, IP, PDE, PA and ETE were computed to examine the HAT, SET-PT and SPLET mechanisms. Also, the frontier molecular orbitals (FMO) and energies of the studied molecules were computed. Furthermore, the transition wavelengths λ (nm), oscillator strengths (f), the major components of the molecular orbital (MO) transitions and configuration interaction (CI) were computed to elucidate the UV filtering ability of the investigated compounds. This study will serve as a base to create an awareness of the photoprotective properties of the compounds studied possible design and applications as sunscreen products.
2. Computational Details
All calculations in this study were done with the ORCA 4.2.1 program suite   . Initial guess geometries were conceived by means of the Avogadro 1.2.1 visualization program  . For all reported calculations, a tight self-consistent field (SCF) criterion was utilized with a grid6 sized numerical quadrature. The restricted Kohn-Sham (RKS) formalism and its unrestricted counterpart (UKS) were adopted for closed and open-shell molecules (i.e. for radicals and radical cation species) respectively. The geometry of each drometrizole molecule (ArOH), their corresponding radicals (ArO•), cationic radicals (ArOH•+) and anions (ArO−) were optimized in the gas phase with no constraints, using the low-cost B97-3c method. This method was used thanks to its efficient performance in geometry optimization and frequency calculations of organic, inorganic, and organo-metallic systems  . Only real frequencies were obtained from vibrational frequency calculations at the same level of theory as that used for geometry optimization, confirming the optimized geometries are minima on their potential energy surfaces. In all cases, no spin contamination was found.
The electronic energies from the B97-3c method were enhanced via single-point (SP) computations at a higher level of theory using the Minnesota exchange-correlation (XC) functional, M06-2X  , together with the 6-311++G(d,p) basis set. The M06-2X functional was used owing to its reliability in calculating thermodynamic parameters  . The D3 dispersion correction with zero damping (D3Zero) was employed to justify long-range dispersion interactions in all SP calculations with the M06-2X functional. The resolution-of-identity (RI-J) approximation  and the Chain-of-Spheres (COSX) approximation  , establishing the RIJCOSX approximation, were utilized with the suitable auxiliary basis sets to fasten the SP computations. Remarkably, the loss of accuracy from applying the RIJCOSX approximation is insignificant  . Reaction enthalpies were computed M06-2X/6-311++G(d,p) level of theory, by making use of the electronic energies obtained at this level with vibrational frequencies obtained from the B97-3c method, with the aid of the Kisthelp software.
To include solvent effects on the computed properties, a continuum solvation method termed Solvation Model Density (SMD) was employed  via SP calculations on the gas-phase optimized B97-3c geometries. SMD was used owing to its universal and applicable nature for any charged or uncharged solutes, with relatively low errors  . Water (dielectric constants, ε = 78.35) was used to mimic the aqueous environment.
Frontier molecular orbital energies of the studied molecules were obtained from the SP calculations. The HOMO-LUMO energy gaps (ΔE) of the studied compound were calculated based on the energies of the highest and lowest occupied molecular orbitals (EHOMO and ELUMO, respectively) as follows:
To compute the absorption spectra of the studied compounds, vertical electronic excitations from the minima of the ground-state structures were computed using the PBE0 functional  with the def2-TZVP Ahlrichs triple-ζ basis set  , employing the time-dependent density functional theory (TD-DFT) as implemented in the ORCA software. PBE0 has been utilized because it produces computed values which corroborate their experimental counterparts  . The def2-TZVP basis set was employed since it is appropriate to compute electronic properties  . To account for long-range dispersion interactions, the Grimme’s atom-pairwise dispersion correction with Becke-Johnson damping (D3BJ)  was employed. Using the TD-DFT method, electronic absorption properties (like the transition wavelengths λ (nm), oscillator strengths (f), the major components of the molecular orbital (MO) transitions and configuration interaction (CI)) of the studied compounds on the basis of the B97-3c optimized ground state geometries were obtained.
2.1. Antioxidant Potential
As stated before now the antioxidant capacity of phenolic compounds has been elucidated through several mechanisms. The commonly used ones are hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET)  . These mechanisms individually offer an approach on how these molecules respond in the presence of a radical   . It is worth noting that the previously mentioned mechanisms are liable to happen in parallel, however, at different rates. The above-mentioned mechanisms are presented in Figure 2 and have been briefly discussed below.
2.1.1. Hydrogen Atom Transfer (HAT) Mechanism
This mechanism is characterized by the capacity of a free radical (R•) to remove a hydrogen atom from the antioxidant (ArOH), yielding the radical form of phenolic antioxidant (ArO•).
2.1.2. Single Electron Transfer-Proton Transfer (SET-PT) Mechanism
The SET-PT mechanism is a two-step reaction. The first step is ruled by the ability of an antioxidant to transfer an electron, giving rise to a cationic radical (ArOH•+).
Figure 2. (a) HAT, (b) SET-PT and (c) SPLET mechanisms of the studied compounds.
In the second step, the ArOH•+ previously formed is deprotonated into a phenolic radical (ArO•).
The numerical descriptors resulting from this mechanism are IP and PDE for the first and second reactions respectively.
2.2. Sequential Proton Loss Electron Transfer (SPLET) Mechanism
Like the SET-PT mechanism, the SPLET mechanism also consists of a two-step reaction. The first step corresponds to the deprotonation of the phenolic antioxidant, yielding the antioxidant anion (ArO−).
The second step corresponds to the transfer of an electron form ArO−, resulting in the formation of the phenoxyl radical (ArO•) of the antioxidant.
The numerical descriptors resulting from this mechanism are PA and ETE for the first and second steps respectively.
To investigate the likelihood of these mechanisms to occur, related thermodynamic parameters comprising: O-H bond dissociation enthalpy (O-HBDE), ionization potential (IP), proton dissociation enthalpy (PDE), proton affinity (PA), and the electron transfer enthalpy (ETE) were assessed according to Equations (7-8) as:
where , , , , , , and are enthalpies of the neutral molecule (antioxidant), neutral radical, hydrogen atom, radical cation, anion, electron, and proton, respectively. The gas phase , and values for this study were obtained from    , while those of , and in the aqueous phase from  . The in the gaseous and aqueous phases for this study were computed at the M06-2x/6-311++G(d,P) level of theory.
3. Results and Discussion
3.1. Investigating the Suitability of the Optimized Structures
In order to assess the suitability of the B97-3c method and the accuracy of the optimized structures, a selection of gas-phase calculated bond lengths and angles of PBT have been likened to the corresponding experimental values obtained elsewhere  . The computed bond lengths and angles of PBT are enumerated in Table S1 of the electronic Supplementary Information (ESI), alongside their corresponding experimental values. It can be perceived from Table S1 that the theoretical bond lengths and angles agree with experimental data, indicating the suitability of the method used. For better comparison of these values, Pearson’s linear regression was performed. Correlation coefficients (R2) of 0.99 and 0.93 were found for the bond angles and bond lengths respectively. From the high R2 values (very close to unity), the calculated bond lengths and bond angles of PBT agree perfectly with the experimental values, indicating the reliability of the optimized structures.
3.2. Geometrical Analyses
The fully optimized B97-3c geometries of the neutral forms of PBT, PBT1 and PBT2 in the gaseous phase are shown in Figure 3. Those of the corresponding radical, cationic radical and anionic forms are included in the accompanying ESI as visualized with the ChemCraft v1.7 software  . The Cartesian coordinates for all these structures are provided in the ESI. Selected geometric parameters of these molecules are listed in Table 1 (see Figure 1 for atom numbering). The selected parameters presented in Table 1 originate from the 4-methoxy phenolic ring, as changes caused by the ED and EASs at the ortho position (C17 atom) of this ring, may yield some loss of planarity of PBT. As can be observed from the values presented in Table 1 it is obvious that the type of substituents (i.e. EDS and EASs) on C17 of the 4-methoxy phenolic ring does not have a significant effect on the selected geometrical parameters. Also, it is inferred from the bond
Figure 3. Optimized structures of the studied compounds obtained from B97-3c calculations in gas phase.
Table 1. Selected geometric parameters of PBT and ortho-substituted optimized with the B97-3C method gaseous phase.
length values listed in Table 1 that for each molecule investigated, the numerical values are close to 120˚, suggesting that the atoms in the 4-methoxy phenol ring are nearly sp2 hybridized and are therefore very likely to adopt a highly planar arrangement. That notwithstanding, the planarity of these molecules is likely to be significantly reduced owing to free-rotation around the N12-C14 bond. Nevertheless, the rotation is highly hindered by the intramolecular hydrogen bonds O16-H22⋯N11 which also stabilize the molecules. Also, from the torsional angles in the 4-methoxy phenolic ring listed in Table 1 are close to 0˚ or 180˚. On the basis of the ongoing, the optimized molecular geometries of the studied molecules are highly planar and there is no significant effect with the presence of the EDS and EASs.
3.3. Antioxidant Properties of the Studied Molecules
In this study, the relative values are referred to those of phenol, generally designated as the zero compound  .
3.3.1. Evaluation of the HAT Mechanism
As earlier mentioned, O-HBDE is the numerical parameter related to the HAT mechanism. It characterizes the stability of the corresponding hydroxyl group. Lower O-HBDE values designate lower stability and the ease to which the equivalent O-H bond is broken, giving rise to a higher antioxidant activity  . The O-HBDE values of the studied molecules were calculated from Equation (2) and the results are presented in Table 2 in the gas and aqueous phases. As can be seen from Table 2, the O-HBDE values of the molecules under study are larger in the gaseous phase (by about 21 kJ/mol), implying that H-atom abstraction is more difficult in the gaseous phase.
It is also found in Table 2 that the difference between the O-HBDE values of PBT and that PBT1 is approximately 42 and 46 kJ/mol, while that with PBT2 is about −6 and −9 kJ/mol in the gas and aqueous phases respectively. This means that the presence of -NH2 lowers the O-HBDE values, while that of -CN increases this value as compared to that of PBT. This variation is attributed to the fact
Table 2. Computed O-H bond dissociation energies (O-HBDE) (in kJ/mol) of the studied compounds obtained at the M06-2x-D3(BJ)/6-311++G(d,p) level of theory.
aRefer to phenol for the relative O-HBDE values (in the parentheses).
that EASs in the ortho-position stabilize the parent molecule and destabilize the radical, causing a rise in the O-HBDE values. Contrariwise, EDSs in ortho-position have an opposite effect, leading to a reduction in the O-HBDE values. The O-HBDE values of the studied compounds were compared to that of phenol at the same theoretical level, and it is observed that PBT1 has a lower value (by about 16 and 45 kJ/mol in both study environments respectively). This clearly shows that PBT1 has a better antioxidant potential than phenol. In all investigated media, the lowest O-HBDE was recorded for PBT1, while the highest for PBT2. This implies that H-atom abstraction is easier in PBT1 and more difficult in PBT2. On the basis of the O-HBDE and the HAT mechanism, the antioxidant activity decreases as follows: PBT1 > PBT > PBT2 in all studied medium.
Spin density distributions
The spin density distribution is a well-grounded parameter that offers a better illustration of the reactivity of a radical system. Lower spin density distribution values yield a higher delocalization of the spin density in a given radical. The computed spin densities on the oxygen atom of the phenoxy radicals (PBT, PBT1 and PBT2) in the gas and aqueous phases are presented in Table 3. Results from this table indicate that the spin density on the oxygen atom of the PBT1 radical is lower than those of the PBT and PBT2 radicals in both studied environments, implying that radical PBT1 has the highest stability and consequently is the least reactive in radical reactions. This result is allied to the lowest O-HBDE values of PBT1 from Table 2, whereby PBT1 is the best antioxidant molecule.
3.3.2. Evaluation of the SET-PT Mechanism
As stated earlier, the ionization potential (IP) and proton dissociation enthalpy (PDE) are the descriptors associated with the two-step SET-PT mechanism. Molecules with low IP values are more susceptible to ionization and have potent antioxidant properties. The lower the IP value for a given molecule, the higher its electron donating ability and higher antioxidant activity  . For this study, the IP and PDE values of the molecules studied were computed from Equations (3) and (4) respectively and the values alongside that of phenol in the vacuum and aqueous phase are listed in Table 4. In this table, it is evident that the IP values of the compounds under study are less than that of phenol in both studied environments. Implying that the investigated molecules have a greater tendency to give out electrons than phenol and consequently have better antioxidant properties than the latter. From this table, the difference between the IP value of PBT
Table 3. Spin density values on the O-radical of the studied compounds computed at the at the M06-2x-D3(BJ)/6-311++G(d,p) level of theory.
Table 4. Computed ionization potential (IP) and proton dissociation energies (PDE) (in kJ/mol) of the studied compounds obtained at the M06-2x-D3(BJ)/6-311++G(d,p) level of theory.
bRefer to phenol for the relative IP and PDE values (in the parentheses); cRefer to phenol for the relative PDE values (in the parentheses).
and PBT1 is 66 kJ/mol in both media while that of PBT and PBT2 are −45 and −30 kJ/mol in the gas and aqueous respectively. Clearly, from Table 4, the lowest IP value was found to be for PBT1 while the highest for PBT2 in all studied environments. This indicates that PBT1 has the greatest ability to donate electrons while the reverse is true for PBT2. Additionally, Table 4 shows that the presence of the EDS reduces the IP values, while that of the EAS increases this value as compared to that of PBT in both media. The increase in the IP values is attributed to the fact the EAS stabilizes the parent molecule and destabilizes ArOH•+, while the decrease in IP values is due to the fact that the EDS tends to stabilize ArOH•+ and destabilize the parent molecule.
Also, it can be seen in Table 4 that the formation of ArOH•+ for the molecules under investigation is easier in water (by about 255 kJ/mol). This indicates that the formed radical cation, ArOH•+ is more stable in water due to the delocalization of π-electrons. This result agrees with that in  , which confirms that electron donation is easier in the solvent, particularly polar medium (water in this case). On the basis of the ongoing, the increasing IP trend is: PBT1 < PBT < PBT2.
PDE describes the potential of the cationic radical, ArOH•+ to transfer a proton to the free radical. Molecules with lower PDE values are more susceptible to proton loss  . As can be seen from Table 4, the highest PDE values are found for PBT1, whereas lowest for PBT2. This observation is as a result of the fact that the presence of the EDS in PBT1 stabilizes ArOH•+ but destabilizes the parent molecule, while the presence of the EAS in PBT2 have an opposite effect. These results are in accordance with a previous paper on substituted phenols  . From a thermodynamic view point, the first step (IP) is the most important. From the values reported in Table 4, the SET-PT mechanism is not preferred in the gas phase due to the fact that the IP and PDE values are higher than the corresponding aqueous phase values. The significant decrease in both parameters (predominantly the PDE values) in aqueous phase implies the ease in the proton transfer and electron abstraction processes respectively. This observation is similar to that obtained in  .
3.3.3. Evaluation of the SPLET Mechanism
As earlier mentioned, the proton affinity (PA) and electron transfer enthalpy (ETE) parameters are linked to the SPLET mechanism. The PA and ETE values of the compounds studied were calculated according to Equations (5) and (6) respectively in the gaseous and aqueous phases together with those of phenol are enumerated in Table 5. The proton loss (characterized by the PA values) is the underlying step in the SPLET mechanism. Lower PA values favor the deprotonation of the drometrizole antioxidants yielding the phenoxyl anion. It can be seen from Table 5 that the PA values for all studied compounds are higher in the gaseous phase than in the aqueous phase, suggesting that the proton loss is highly preferred in aqueous phase. In addition, it can be inferred from Table 5 that the PA values of the molecules under investigation are lower than those of phenol.
Electron transfer (characterized by the ETE values) from the phenoxide ion represents the second step in SPLET mechanism. ETE denotes the capacity of the antioxidant anion to transfer electrons to the free radical. The lower the ETE value for a given molecule, the more active is the resulting phenoxide anion. From Table 5, the ETE values in the gas and aqueous phases follow the same sequence: ETEPBT1 < ETEPBT < ETEPBT2. In aqueous media, the ETE values of the studied compounds are higher than the PA values but enough to account for the second step of SPLET mechanism. It is evident from Table 5 that the lowest ETE value corresponds to PBT1 while the highest to PBT2 in all studied environments. This shows that PBT1 has a greater tendency to transfer electrons to the free radical and the ease with which it forms the corresponding phenoxide anion, while the reverse is the case for PBT2. Also, it is obvious from Table 5 that the presence of the EDS in PBT1 decreases the ETE value, while that of the EAS in PBT2 increases this value as compared to PBT. It can also be seen in Table 5 that the formation of the phenoxide anion for the investigated molecules is easier in the aqueous phase than in the gaseous phase. On the basis of the ETE values, PBT1 is the best anti-oxidant molecule, while PBT2 is the least.
Table 5. Computed proton affinities (PA) and electron transfer energies (ETE) (in kJ/mol) of the studied compounds obtained at the M06-2x-D3(BJ)/6-311++G(d,p) level of theory.
dRefer to phenol for the relative PA values (in the parentheses); eRefer to phenol for the relative ETE values (in the parentheses)
To ease comparisons, the O-HBDE, IP and PA values for all the molecules investigated were plotted on the same axes and are presented on Figure 4(a) and Figure 4(b) for the gas and aqueous phases respectively. It is obvious from Figure 4(a) that the computed PA values of the studied molecules are higher than the equivalent IP and O-HBDE values. This illustrates that in the gas phase, the favored mechanism can be classified thermodynamically as: HAT < SET-PT < SPLET. In the same manner, it can be seen from Figure 4(b) that the PA values of the compounds investigated are remarkably lower than the corresponding O-HBDE and IP values. Therefore, in aqueous phase, the SPLET mechanism represents the most probable reaction pathway from thermodynamic point of view. In the aqueous phase, the trend is: SPLET < SET-PT < HAT. This trend ascertains the importance of this mechanism in a polar solvent as reported elsewhere  . Conclusively, among the three mechanisms investigated, the HAT mechanism is thermodynamically favored in the gas phase and SPLET in water.
3.4. Frontier Molecular Orbital (FMO) Analyses
FMOs are important parameters which portray electronic properties as well as reactivity of a molecule. The Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) distribution can equally be utilized to describe the antioxidant capabilities of a molecule  . Knowledge of the HOMO distribution can be used to deduce the probable site for attack by free radicals in the molecule.
As can be seen from Table 6, the HOMO of PBT1 is mainly localized on the 4-methylphenolic moiety, while those PBT and PBT2, are appreciably distributed over their entire molecular structures (i.e. on the 4-methylphenolic and benzotriazole moieties). This suggests the probable sites for radical attack.
On the basis of FMO and the Fukui theories, FMO energies (i.e. EHOMO, and ELUMO are vital to predict chemical reactivity and stability of molecules. The EHOMO
Figure 4. Plot of enthalpy values (kJ/mol) with molecular species in (a) Gas and (b) Aqueous phases computed at the M06-2x-Zero/6-311++G(d,p) level of theory in gas and aqueous phases.
Table 6. HOMO distributions of the studied molecules obtained at the M062x-D3Zero/ 6-311++G(d,p) level of theory.
is another parameter to measure the electron-donating ability of antioxidants. The higher the EHOMO value, the greater the tendency of a molecule to donate electrons is and consequently a higher antioxidant is potential. The HOMO-LUMO energy gap, ΔE in turn provides information on the chemical activity of the molecule. The computed EHOMO, ELUMO and ΔE values of the studied molecules in the gas and aqueous phases are summarized in Table 7.
It can be seen in Table 7 that the presence of the EDS (-NH2) in PBT1 increases EHOMO (i.e. it becomes less negative), while the presence of EAS (-CN) in PBT2 reduces EHOMO (i.e. it becomes more negative) as compared to that of PBT. Consequently, drometrizoles with strong EDSs are better electron-donors, i.e., they easily partake in the SET-PT mechanism than those with EASs. Accordingly, the electron-donating ability of the studied molecules increases in the order: PBT2 < PBT < PBT1. From its relatively high EHOMO values, PBT1 is the most chemically reactive species among the molecules studied. This is attributable to the presence of the -NH2 group at the ortho-position of the -OH group, which acts as an EDS by means of its positive inductive (+I) effect which activates the 4-methoxy phenolic ring, making it more reactive. The IP trend is consistent with the data presented in Table 7, confirming that PBT1 is the best electron-donor among the investigated compounds. From this trend, we conclude that
Table 7. Calculated EHOMO, ELUMO and ΔE (eV) of drometrizole and its ortho-substituted derivatives computed at the M06-2x-D3(BJ)/6-311++G(d,p) level of theory in gas and aqueous phases.
EHOMO can be rapidly used to estimate the reaction enthalpies of the first step of the SET-PT mechanism. These dependences can be used to select appropriate substituents for the synthesis of novel drometrizole-based derivatives with improved antioxidant activity  .
ΔE provides valuable information on the reactivity and stability of molecules   . The ΔE values of species investigated in this work were calculated according to Equation (1). It is obvious from the values reported in Table 7 that PBT1 has the lowest ΔE values while PBT2 has the highest. Accordingly, the transfer of electrons from HOMO to LUMO in PBT1 is relatively easier than in the other studied compounds. Based on the ΔE values of the studied compounds, the order of decreasing ΔE is: ΔEPBT2 > ΔEPBT > ΔEPBT1. This trend is consistent with those obtained from the EHOMO values. PBT1 was predicted to be the most reactive and consequently, has the best antioxidant activity amongst the studied molecules. This result is in perfect agreement with the predicted antioxidant activity as presented in Table 3.
3.5. Computed Electronic Absorption Spectra of the Studied Compounds
To assess the ability of PBT to screen UV radiations and the effect of ED and EASs, their electronic absorption spectra were simulated at the TD-DFT/PBE0-D3(BJ)/ def2-TZVP levels of theory in gas and aqueous (water solvent) phases. The spectral data obtained is presented in Table 8. Listed in Table 8 are the vertical absorption transition wavelengths (λabs in nm), the oscillator strengths (f), the configuration interaction (CI) or molecular orbital percentage contributions, and the prominent electronic transitions. As can be seen in Table 8, two absorption bands with the maximum band centered around 334, and the shoulder band around 282 nm are observed in the absorption spectrum of PBT in both the gas and water solvent. These bands correspond to S0→S1 and S0→S2 transitions respectively. Interestingly, these values are very close to the experimentally obtained absorption spectrum of PBT obtained in  , which shows two intense bands centered around 330 and 280 nm. This result confirms the suitability of the level of theory used. The relatively high oscillator strengths of the calculated electronic transitions indicate their high intensities. The observed transitions: S0→S1, and S0→S2 originate from the molecular orbitals: HOMO (H), HOMO-2 (H-2)
Table 8. Transition wavelengths λ (nm), oscillator strengths (f), the major components of the molecular orbital (MO) transitions and configuration interaction (CI) for PBT and derivatives computed at PBE0-D3(BJ)/def2-TZVP level of theory.
and HOMO-1 (H-1), respectively, and terminate in the molecular orbital LUMO (L) in each case. In the gas phase, the maximum absorption is due to the transition from H→L and the shoulder peak due to transitions from H-2→L. In water, the maximum absorption is due to the transition from H→L and the shoulder peak due to the H-1→L transitions. It is evident from the results obtained that PBT has an absorption in the region 283 - 340 nm, and can effectively absorb the dangerous UV A and UV B radiations from sunlight. This result is in accordance with that obtained elsewhere  .
Further search for enhanced UV filter molecules based on the drometrizole moiety led to the absorption spectra of the designed drometrizole derivatives studied and the results are presented in Table 8.
From this table, two intense absorption bands with the maximum band centered around 361, and the shoulder band around 301 nm in both the gas and water solvent are visible. These bands like those for PBT correspond to the S0→S1 and S0→S2 transitions respectively. These transitions correspond to the H→L and H-1→L for the maximum absorption and the shoulder peak respectively in both environments studied. It is also observed from Table 8 that all the absorption bands are red shifted as compared to that of PBT by factors of 33 and 21 nm for the maximum absorption and the shoulder peaks respectively in both environments under study. This bathochromic shift results from the presence of the EDS (-NH2) at the ortho-position of the -OH group on the drometrizole moiety i.e. corresponding to PBT1. No significant change is observed for the molecules obtained from substitutions at the ortho-position with the presence of the EAS (-CN) i.e. the PBT2 molecule. It is important to point out that the derivatives of PBT have absorptions in the region 288 - 395 nm, implying that they can readily absorb the hazardous UV A and UV B radiations from sunlight.
On the basis of the ongoing, the studied compounds especially PBT1 are potential candidates for the manufacture of UV filters and sunscreen lotions to fight the devastating effects of UV A and UVB radiations.
The antioxidant and UV spectral characteristics of Drometrizole (PBT) and the effect of an electron-donating group (ED), -NH2 and an electron-attracting group (EA), -CN groups on these properties have been analyzed theoretically in the gas and aqueous phases. From a thermodynamic perspective, the HAT mechanism is preferred in the gas phase, while SPLET in the aqueous phase. Also, it is observed that the presence of -NH2 reduces the O-HBDE and IP values, while that of -CN increases the PA values. Consequently, the molecule with the ED substituent (PBT1) is identified to be the compound with the highest antioxidant activity among the studied molecules. The spin density values on the O-radical are the lowest for PBT1 confirming that it is the best antioxidant molecule. The UV spectra of these molecules exhibit two intense absorption bands within the 280 - 400 nm region. This corresponds to the UV A and UV B regions of the electromagnetic spectrum. The major transitions in the UV-Visible spectra of the studied compounds are between the HOMO, HOMO-1 and HOMO-2 with LUMO level. The presence of the ED substituent is found to cause a bathochromic shift in absorption wavelengths. The studied molecules especially PBT1 can thus be considered as a potent antioxidant and UV absorption agent. The antioxidant capability of these molecules is therefore an added advantage for photoprotection as they can scavenge the free radicals. Results from this study can further be used for the design and synthesis of compounds with more improved photoprotective properties for applications in sunscreen products. Also, this study gives way for a subsequent kinetic study to make perfect the results deduced from this thermodynamic study.
We gratefully acknowledge the annual research modernization grant to lecturers by the Ministry of Higher Education of Cameroon.
aRefer to Figure 1 for atom numbering. bExperimental values of selected bond lengths and angles. cComputed values of selected bond lengths and angles from this work using the B97-3c method.
Table S2. Enthalpies (in kJ/mol) of the electron , proton and hydrogen atom used in this study at the M06-2x/6-311++G(d,p) level of theory.
Table S3. Enthalpies (in kJ/mol) of the neutral molecules used in this studied as computed at the M06-2x/6-311++G(d,p) level of theory.
Table S4. Enthalpies (in kJ/mol) of the radical species of the molecules under investigation used in this studied as computed at the M06-2x/6-311++G(d,p) level of theory.
Table S5. Enthalpies (in kJ/mol) of the cationic radical species of the molecules under investigation used in this studied as computed at the M06-2x/6-311++G(d,p) level of theory.
Table S6. Enthalpies (in kJ/mol) of the anionic species of the molecules under investigation used in this studied as computed at the M06-2x/6-311++G(d,p) level of theory.
Table S7. Cartesian coordinates of the gas phase optimised geometry of neutral form of PBT.
Table S8. Cartesian coordinates of the gas phase optimised geometry of neutral form of PBT1.
Table S9. Cartesian coordinates of the gas phase optimised geometry of neutral form of PBT2.
Table S10. Cartesian coordinates of the gas phase optimised geometry of PBT radical.
Table S11. Cartesian coordinates of the gas phase optimised geometry of PBT1 radical.
Table S12. Cartesian coordinates of the gas phase optimised geometry of PBT2 radical.
Table S13. Cartesian coordinates of the gas phase optimised geometry of PBT cationic radical.
Table S14. Cartesian coordinates of the gas phase optimised geometry of PBT1 cationic radical.
Table S15. Cartesian coordinates of the gas phase optimised geometry of PBT2 cationic radical.
Table S16. Cartesian coordinates of the gas phase optimised geometry of the anionic form of PBT.
Table S17. Cartesian coordinates of the gas phase optimised geometry of the anionic form of PBT1.
Table S18. Cartesian coordinates of the gas phase optimised geometry of the anionic form of PBT2.
Table S19. Cartesian coordinates of the gas phase optimised geometry of neutral form of Phenol.
Table S20. Cartesian coordinates of the gas phase optimised geometry of Phenolic radical.
Table S21. Cartesian coordinates of the gas phase optimised geometry of Phenolic cationic radical.
Table S22. Cartesian coordinates of the gas phase optimised geometry of the Phenolic anion.
Figure S1. Optimized structures of the radicals of the studied compounds obtained from B97-3c calculations in gas phase.
Figure S2. Optimized structures of the cationic radicals of the studied compounds obtained from B97-3c calculations in gas phase.
Figure S3. Optimized structures of the anionic forms of the studied compounds obtained from B97-3c calculations in gas phase.
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