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Antioxidant activity of some phenolic aldehydes and their diimine derivatives: A DFT study
Accepted Manuscript Antioxidant Activity of Some Phenolic Aldehydes and Their Diimine Derivatives: A DFT Study Romesh Borgohain, Ankur Kanti Guha, Sanjay Pratihar, Jyotirekha G. Handique PII: DOI: Reference:
S2210-271X(15)00085-7 http://dx.doi.org/10.1016/j.comptc.2015.02.014 COMPTC 1749
To appear in:
Computational & Theoretical Chemistry
Received Date: Revised Date: Accepted Date:
14 December 2014 21 January 2015 6 February 2015
Please cite this article as: R. Borgohain, A.K. Guha, S. Pratihar, J.G. Handique, Antioxidant Activity of Some Phenolic Aldehydes and Their Diimine Derivatives: A DFT Study, Computational & Theoretical Chemistry (2015), doi: http://dx.doi.org/10.1016/j.comptc.2015.02.014
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Antioxidant Activity of Some Phenolic Aldehydes and Their Diimine Derivatives: A DFT Study Romesh Borgohaina, Ankur Kanti Guhab, Sanjay Pratiharc and Jyotirekha G. Handiquea* a
Department of Chemistry, Dibrugarh University, Dibrugarh-786004, Assam, India
b
Department of Chemistry, Indian Institute of Technology, Kanpur, Uttar Pradesh, India-
208016 c
Department of Chemical Sciences, Tezpur University, Tezpur, Assam, India-784028
*Corresponding author. Tel: +91 373 2370210 (O); Email: [email protected]
1. INTRODUCTION The antioxidant activity of a compound indicates its ability to inhibit or prevent the oxidation of oxidizable material by scavenging free radicals like ROS (Reactive Oxygen Species), RNS (Reactive Nitrogen Species) and thereby protects the body from oxidative damage caused by the free radicals [1]. There are mainly two pathways through which antioxidants can scavenge the free radicals viz., (1) hydrogen atom transfer (HAT) and (2) single electron transfer (SET) mechanism. Bond dissociation energy (BDE) and ionization potential (IP) are the key factors that determine the mechanism and efficiency of antioxidants [2]. However, two other mechanisms of radical scavenging known as single electron transfer followed by proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET) may also occur [3]. HAT-based mechanism involves the measurement of the classical ability of an antioxidant to scavenge free radicals by hydrogen donation to form stable compounds. This mechanism is more relevant to the radical chain breaking antioxidant capacity.
AH + R RH + A (Where AH = any hydrogen donor and R is a radical. And A is more stable than R) Relative reactivity of HAT mechanism is determined by the bond dissociation energy of the H-donating group in the potential antioxidant. HAT reactions are solvent and pH dependent and are generally quite rapid, typically completed in seconds to minutes. SET-based mechanism deals with the ability of a potential antioxidant to transfer one electron to reduce any compounds, including metals, carbonyls and radicals; M(III) + AH AH + M(II) Deprotonation and ionization potential of the reactive functional group determines the relative reactivity in SET-based mechanism. SET reactions are pH dependent showing a decrease with increasing pH, reflecting increased electron donating capacity with deprotonation. In comparison to HAT, the SET mechanism is strongly solvent dependent due to solvent stabilization of the charged species [4,5]. In SET-PT mechanism, the first step involves the transfer of an electron from the antioxidant to form a radical cation and in the next step, deprotonation from the radical cation occurs. AH AH+ + eAH+ A + H+ Again, in SPLET mechanism loss of proton from the antioxidant occurs followed by transfer of an electron. AH A- + H+ A- A + eThus, compounds having antioxidant property can scavenge free radicals by releasing their phenolic hydrogen atoms following these four mechanisms. It is to be noted that all these mechanisms may or may not co-exist and they are dependent upon the
solvent properties and radical characters. However, the net result of all these mechanisms is same [3]. Phenolic compounds have great importance as antioxidants to inhibit the oxidation of materials having commercial and biological importance [6]. They possess different antioxidant activity potentials because of their phenolic hydroxyl groups which can act as a hydrogen or electron donor [7]. Thus they are used as universal remedy for a wide range of lifestyle-related diseases such as early aging, cancer, diabetes, cardiovascular and other degenerative diseases [8]. With the development of quantum chemistry and computational methodologies, it becomes easier to calculate BDEs and IPs with accuracy equivalent to or greater than those obtained from experiments. Therefore, theoretical calculations could be used as a useful tool for predicting antioxidant activity of compounds as well as to design novel potential antioxidants. Wright and his co-workers [2] studied the antioxidant activity of various phenolic compounds using density functional theory and made a comparison between HAT and SET mechanisms. They concluded that HAT mechanism predominates in most cases [5]. Reis and his co-workers also theoretically evaluated the antioxidant activity of various phenolic compounds using different levels of calculations [9]. Again, Javan et. al. investigated computationally the H-atom vs electron transfer mechanism for antioxidant activity of some bromophenols and compared their observation to those for which the antioxidant activity was previously evaluated [10]. Analysis of antioxidant activity of various gallic acid derivatives as well as the values of some density–based reactivity descriptors was carried out by Kar et. al. and they found that phenolic compounds are more stable in gas phase than in solvent medium [11]. The antioxidant radical scavenging capacity of pyranoanthocyanins was investigated by Russo et. al. [12] They reported that compounds forming radicals, which are stabilized by intramolecular H-
bonds, generally favors HAT mechanism while compounds having a higher degree of electron delocalization favors SET mechanism. Similarly, theoretical calculations were performed by Mohajeri et. al. to predict the antioxidant activity of some compounds like phenolic acids, vitamins etc. and they found that in case of HAT mechanism, antioxidants with lower BDE undergo hydrogen abstraction with low barrier and considerable exothermicity [13]. Alberto et. al studied the antioxidant character of trolox in different solvents using DFT. They considered several reaction mechanisms and different chemical nature of the free radicals and found good agreement of their results with experimentally available data [14]. Again, Leopoldini et. al investigated the effectiveness of caffeic acid in scavenging hydroxyl radical using hybrid density functional theory. They also analyzed different pathways of radical scavenging and concluded that caffeic acid is a very good radical scavenger[15]. Thus, study of the antioxidant capacity of phenolic compounds and their derivatives is continuing and expected to be continued in future. Several theoretical and experimental works have been performed to evaluate the antioxidant activity of the phenolic compounds [16-20]. In our present study, we have chosen three plant-based phenolic aldehydes [21-23] viz., 3-hydroxybenzaldehyde (I), 3,4-dihydroxybenzaldehyde (II) and vanillin (III), having antioxidant property and designed some diimines [24,25] using three ,-diamines of different spacer lengths viz., 1,2-diaminoethane (IV), 1,4-diaminobutane (V) and 1,6diaminohexane (VI) (Scheme 1). We have calculated the O-H bond dissociation energy (BDE) and vertical ionization potentials (IP V) of these derivatives (Scheme 1). Since, antioxidants generally work in the physiological liquids, we therefore, included water alongwith benzene (having dielectric constants of 80 and 2.25 respectively) in our calculations. Compounds are named as shown in Scheme 1. For example, diimines of 3hydroxybenzaldehyde (I) with n = 1, 2 and 3 will be referred to as Ia, Ib and Ic
respectively and the corresponding radical of (I) will be referred to as I-rad. Similarly, the diimine of 3,4-dihydroxybenzaldehyde (II) with n = 1 will be referred to as IIa and its corresponding radical will be referred to as IIa-rad. 2. COMPUTATIONAL DETAILS All the structures were fully optimized at gradient corrected BP86 level of theory [26]. We used both 6-31+G(d) and 6-311++G(d,p) basis set for all the atoms. Frequency calculations were performed at the same level of theory to characterize the nature of the stationary points. All the structures were found to be local minimum with real values of frequencies. Vertical ionization potential IP v, has been calculated by running single point calculations by taking the optimized geometry of the neutral and the cation at the same geometry of the neutral. All the calculations were performed using the Gaussian03 suite of program [27]. We have also calculated single point energy calculation at B3LYP/6311++G(d,p) on the optimized geometries to calculate BDE. Natural bond orbital (NBO) calculations have been performed at BP86/6-31+G(d) level of theory to characterize the electronic structures of these molecules [28]. Hyperconjugation increases the stability of these compounds and hence, stability arising from hyperconjugation has been calculated using the NBO method. Hyperconjugation arising from the overlap between the occupied and unoccupied orbital leads to a stability of the molecules when these orbitals are properly oriented. This interaction can be quantitatively expressed by the second-order perturbation interaction energy (E2) [29]. It can be deduced from the second-order perturbation approach:
where qi is the donor orbital occupancy, εi, εj are diagonal elements (orbital energies), and F(i, j) is the off-diagonal NBO Fock matrix element. Spin densities of the radicals were
calculated at BP86/6-31+G(d) level of theory and plotted to examine the extent of delocalization of the unpaired electron throughout the molecular systems. Solvent effects were computed within the framework of polarized continuum model (PCM) as implemented in Gaussian 03 [30] in BP86/6-31+G(d) level of theory. Owing to the nature of phenolics studied with different spacer lengths (Scheme 1), conformational flexibility is expected. Hence, we also included dispersion correction of Grimme et al using the ωB97XD [31,32] to check the conformational flexibility of some molecules (Ia-c, IIa and IIIb, Scheme 1). 3. RESULTS AND DISCUSSION 3.1 Bond Dissociation Energies (BDE) and Ionization Potentials (IP V): To calculate the BDE and IP V values, minimum energy conformations calculated at BP86/6-31+G(d) are used. Further, dispersion corrected functional such as ωB97XD has been used to reoptimize some of the structures (Ia-c, IIa and IIIa in Scheme 1). It is interesting to note that the minimum energy conformations of these molecules are almost similar. Figure 1 represents the minimum energy conformations calculated at BP86 and ωB97XD level of theory using the 6-31+G(d) basis set. It is evident from Figure 1 that there is very minor change in the dihedral angles in the minimum energy structures after addition of dispersion correction. Thus, it is expected that the geometries of these molecules will not show major conformational changes after addition of dispersion correction and hence, discussion of the rest of the text will be based on BP86 results.
S2210-271X(15)00085-7 http://dx.doi.org/10.1016/j.comptc.2015.02.014 COMPTC 1749
To appear in:
Computational & Theoretical Chemistry
Received Date: Revised Date: Accepted Date:
14 December 2014 21 January 2015 6 February 2015
Please cite this article as: R. Borgohain, A.K. Guha, S. Pratihar, J.G. Handique, Antioxidant Activity of Some Phenolic Aldehydes and Their Diimine Derivatives: A DFT Study, Computational & Theoretical Chemistry (2015), doi: http://dx.doi.org/10.1016/j.comptc.2015.02.014
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Antioxidant Activity of Some Phenolic Aldehydes and Their Diimine Derivatives: A DFT Study Romesh Borgohaina, Ankur Kanti Guhab, Sanjay Pratiharc and Jyotirekha G. Handiquea* a
Department of Chemistry, Dibrugarh University, Dibrugarh-786004, Assam, India
b
Department of Chemistry, Indian Institute of Technology, Kanpur, Uttar Pradesh, India-
208016 c
Department of Chemical Sciences, Tezpur University, Tezpur, Assam, India-784028
*Corresponding author. Tel: +91 373 2370210 (O); Email: [email protected]
1. INTRODUCTION The antioxidant activity of a compound indicates its ability to inhibit or prevent the oxidation of oxidizable material by scavenging free radicals like ROS (Reactive Oxygen Species), RNS (Reactive Nitrogen Species) and thereby protects the body from oxidative damage caused by the free radicals [1]. There are mainly two pathways through which antioxidants can scavenge the free radicals viz., (1) hydrogen atom transfer (HAT) and (2) single electron transfer (SET) mechanism. Bond dissociation energy (BDE) and ionization potential (IP) are the key factors that determine the mechanism and efficiency of antioxidants [2]. However, two other mechanisms of radical scavenging known as single electron transfer followed by proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET) may also occur [3]. HAT-based mechanism involves the measurement of the classical ability of an antioxidant to scavenge free radicals by hydrogen donation to form stable compounds. This mechanism is more relevant to the radical chain breaking antioxidant capacity.
AH + R RH + A (Where AH = any hydrogen donor and R is a radical. And A is more stable than R) Relative reactivity of HAT mechanism is determined by the bond dissociation energy of the H-donating group in the potential antioxidant. HAT reactions are solvent and pH dependent and are generally quite rapid, typically completed in seconds to minutes. SET-based mechanism deals with the ability of a potential antioxidant to transfer one electron to reduce any compounds, including metals, carbonyls and radicals; M(III) + AH AH + M(II) Deprotonation and ionization potential of the reactive functional group determines the relative reactivity in SET-based mechanism. SET reactions are pH dependent showing a decrease with increasing pH, reflecting increased electron donating capacity with deprotonation. In comparison to HAT, the SET mechanism is strongly solvent dependent due to solvent stabilization of the charged species [4,5]. In SET-PT mechanism, the first step involves the transfer of an electron from the antioxidant to form a radical cation and in the next step, deprotonation from the radical cation occurs. AH AH+ + eAH+ A + H+ Again, in SPLET mechanism loss of proton from the antioxidant occurs followed by transfer of an electron. AH A- + H+ A- A + eThus, compounds having antioxidant property can scavenge free radicals by releasing their phenolic hydrogen atoms following these four mechanisms. It is to be noted that all these mechanisms may or may not co-exist and they are dependent upon the
solvent properties and radical characters. However, the net result of all these mechanisms is same [3]. Phenolic compounds have great importance as antioxidants to inhibit the oxidation of materials having commercial and biological importance [6]. They possess different antioxidant activity potentials because of their phenolic hydroxyl groups which can act as a hydrogen or electron donor [7]. Thus they are used as universal remedy for a wide range of lifestyle-related diseases such as early aging, cancer, diabetes, cardiovascular and other degenerative diseases [8]. With the development of quantum chemistry and computational methodologies, it becomes easier to calculate BDEs and IPs with accuracy equivalent to or greater than those obtained from experiments. Therefore, theoretical calculations could be used as a useful tool for predicting antioxidant activity of compounds as well as to design novel potential antioxidants. Wright and his co-workers [2] studied the antioxidant activity of various phenolic compounds using density functional theory and made a comparison between HAT and SET mechanisms. They concluded that HAT mechanism predominates in most cases [5]. Reis and his co-workers also theoretically evaluated the antioxidant activity of various phenolic compounds using different levels of calculations [9]. Again, Javan et. al. investigated computationally the H-atom vs electron transfer mechanism for antioxidant activity of some bromophenols and compared their observation to those for which the antioxidant activity was previously evaluated [10]. Analysis of antioxidant activity of various gallic acid derivatives as well as the values of some density–based reactivity descriptors was carried out by Kar et. al. and they found that phenolic compounds are more stable in gas phase than in solvent medium [11]. The antioxidant radical scavenging capacity of pyranoanthocyanins was investigated by Russo et. al. [12] They reported that compounds forming radicals, which are stabilized by intramolecular H-
bonds, generally favors HAT mechanism while compounds having a higher degree of electron delocalization favors SET mechanism. Similarly, theoretical calculations were performed by Mohajeri et. al. to predict the antioxidant activity of some compounds like phenolic acids, vitamins etc. and they found that in case of HAT mechanism, antioxidants with lower BDE undergo hydrogen abstraction with low barrier and considerable exothermicity [13]. Alberto et. al studied the antioxidant character of trolox in different solvents using DFT. They considered several reaction mechanisms and different chemical nature of the free radicals and found good agreement of their results with experimentally available data [14]. Again, Leopoldini et. al investigated the effectiveness of caffeic acid in scavenging hydroxyl radical using hybrid density functional theory. They also analyzed different pathways of radical scavenging and concluded that caffeic acid is a very good radical scavenger[15]. Thus, study of the antioxidant capacity of phenolic compounds and their derivatives is continuing and expected to be continued in future. Several theoretical and experimental works have been performed to evaluate the antioxidant activity of the phenolic compounds [16-20]. In our present study, we have chosen three plant-based phenolic aldehydes [21-23] viz., 3-hydroxybenzaldehyde (I), 3,4-dihydroxybenzaldehyde (II) and vanillin (III), having antioxidant property and designed some diimines [24,25] using three ,-diamines of different spacer lengths viz., 1,2-diaminoethane (IV), 1,4-diaminobutane (V) and 1,6diaminohexane (VI) (Scheme 1). We have calculated the O-H bond dissociation energy (BDE) and vertical ionization potentials (IP V) of these derivatives (Scheme 1). Since, antioxidants generally work in the physiological liquids, we therefore, included water alongwith benzene (having dielectric constants of 80 and 2.25 respectively) in our calculations. Compounds are named as shown in Scheme 1. For example, diimines of 3hydroxybenzaldehyde (I) with n = 1, 2 and 3 will be referred to as Ia, Ib and Ic
respectively and the corresponding radical of (I) will be referred to as I-rad. Similarly, the diimine of 3,4-dihydroxybenzaldehyde (II) with n = 1 will be referred to as IIa and its corresponding radical will be referred to as IIa-rad.
where qi is the donor orbital occupancy, εi, εj are diagonal elements (orbital energies), and F(i, j) is the off-diagonal NBO Fock matrix element. Spin densities of the radicals were
calculated at BP86/6-31+G(d) level of theory and plotted to examine the extent of delocalization of the unpaired electron throughout the molecular systems. Solvent effects were computed within the framework of polarized continuum model (PCM) as implemented in Gaussian 03 [30] in BP86/6-31+G(d) level of theory. Owing to the nature of phenolics studied with different spacer lengths (Scheme 1), conformational flexibility is expected. Hence, we also included dispersion correction of Grimme et al using the ωB97XD [31,32] to check the conformational flexibility of some molecules (Ia-c, IIa and IIIb, Scheme 1). 3. RESULTS AND DISCUSSION 3.1 Bond Dissociation Energies (BDE) and Ionization Potentials (IP V): To calculate the BDE and IP V values, minimum energy conformations calculated at BP86/6-31+G(d) are used. Further, dispersion corrected functional such as ωB97XD has been used to reoptimize some of the structures (Ia-c, IIa and IIIa in Scheme 1). It is interesting to note that the minimum energy conformations of these molecules are almost similar. Figure 1 represents the minimum energy conformations calculated at BP86 and ωB97XD level of theory using the 6-31+G(d) basis set. It is evident from Figure 1 that there is very minor change in the dihedral angles in the minimum energy structures after addition of dispersion correction. Thus, it is expected that the geometries of these molecules will not show major conformational changes after addition of dispersion correction and hence, discussion of the rest of the text will be based on BP86 results.
In the HAT mechanism, the bond dissociation energy (BDE) of the O-H bond is an important parameter in evaluating the antioxidant property because the strength of the O-H bonds determines the effectiveness of H abstraction of a particular phenolic compound. This H atom can be transferred to the reactive radical intermediates such as hydroxyl,
alkoxyl, peroxyl, and hydroperoxyl radicals formed during degradation reactions [33]. Table 1 contains BDE values calculated at the BP86/6-31+G(d) level of theory in gas phase and in solvent (water and benzene) medium. It should be noted that the calculated BDE value for phenol (ca. 87.53 kcal/mol in gas phase) deviates from the experimental value by ~1.0 kcal/mol (experimental BDE of phenol is 88.3 ± 0.8) [34]. This might be due to the effect of basis set or functional used. Hence, we also calculated the BDE of phenol at B3LYP [35] using a larger basis set 6-311++G(d,p). The calculated value of BDE at B3LYP/6-311++G(d,p) level of theory is found to be 81.7 kcal/mol which also deviates from the experimental value by ~7.0 kcal/mol. Thus, it appears that BP86/631+G(d) produces better results and hence, in this present work, BP86/6-31+G(d) (in gas phase and in solvents like water, benzene) and BP86/6-311++ G(d,p) (only in gas phase) values are reported owing to the large size of the phenolics considered in this study. Calculations with 6-311++G(d,p) level produces slightly higher BDE values, however, a similar trend with 6-31+G(d) calculated values is maintained. From compound I to II, there is a decrease in BDE with increasing number of –OH group. However, there is again an increase in BDE in case of compound III due to blocking of one –OH group by methyl group. The calculated BDE values (Table 1) are found to be highest in water and lowest in benzene although the differences are not so significant. It is interesting to note that increasing the spacer length via amino substitution decreases the BDE of the phenolics with an exception of (IIIc) where a slight increase in BDE value is observed compared to the parent vanillin. Thus, it is clear that increasing the spacer length results in more favorable H-atom abstraction of the parent phenolic compounds. The calculation of ionization potentials (IP V) of these antioxidants is another important parameter which provides hint towards the possible single electron transfer
(SET) mechanism of these compounds. Lower the value of ionization potential, higher is the probability of a particular compound to undergo single electron transfer resulting in the formation of ArOH•+. The calculated vertical ionization potential (IP V) values of all these phenolics are found to be highest in the gas phase and lowest in water medium. Similar IPV values are obtained with both 6-31+G(d) and 6-311++G(d,p) basis sets. The effect of high solvent polarity on lowering the ionization potential values were previously observed by Belcastro et. Al [36]. This implies that solvent polarity plays a crucial role in dictating the single electron transfer mechanism of an antioxidant. The polarity of the solvent has a significant effect on the IP V values of these compounds unlike BDE values where no such significant variation was observed. Like BDE values, increase in spacer length via amino substitution leads to decrease in IPV values of the phenolics, thereby, favoring single electron transfer. Figure 2 represents the spin density plots of the hydrogen atom-abstracted radicals. It is evident from Figure 1 that the unpaired electron in all these radicals is delocalized to a great extent to the neighboring aromatic rings. This delocalization stabilizes the radicals and makes the phenolic compounds suitable towards hydrogen release to other potent radicals formed during degradation reactions [7] and thus, these phenolic compounds may act as potent antioxidants. The spin density plots of the cationic radicals formed during single electron transfer are shown in supporting information (Figure S1), which also reveals such delocalization. Moreover, Table 2 collects all the energetics arising from the hyperconjugative interaction between the non bonding orbital of oxygen atom to the neighboring σ* or π* orbitals of the C-C bonds of the aromatic rings. This hyperconjugative interaction adds to the stability of these radicals.
alkoxyl, peroxyl, and hydroperoxyl radicals formed during degradation reactions [33]. Table 1 contains BDE values calculated at the BP86/6-31+G(d) level of theory in gas phase and in solvent (water and benzene) medium. It should be noted that the calculated BDE value for phenol (ca. 87.53 kcal/mol in gas phase) deviates from the experimental value by ~1.0 kcal/mol (experimental BDE of phenol is 88.3 ± 0.8) [34]. This might be due to the effect of basis set or functional used. Hence, we also calculated the BDE of phenol at B3LYP [35] using a larger basis set 6-311++G(d,p). The calculated value of BDE at B3LYP/6-311++G(d,p) level of theory is found to be 81.7 kcal/mol which also deviates from the experimental value by ~7.0 kcal/mol. Thus, it appears that BP86/631+G(d) produces better results and hence, in this present work, BP86/6-31+G(d) (in gas phase and in solvents like water, benzene) and BP86/6-311++ G(d,p) (only in gas phase) values are reported owing to the large size of the phenolics considered in this study. Calculations with 6-311++G(d,p) level produces slightly higher BDE values, however, a similar trend with 6-31+G(d) calculated values is maintained. From compound I to II, there is a decrease in BDE with increasing number of –OH group. However, there is again an increase in BDE in case of compound III due to blocking of one –OH group by methyl group. The calculated BDE values (Table 1) are found to be highest in water and lowest in benzene although the differences are not so significant. It is interesting to note that increasing the spacer length via amino substitution decreases the BDE of the phenolics with an exception of (IIIc) where a slight increase in BDE value is observed compared to the parent vanillin. Thus, it is clear that increasing the spacer length results in more favorable H-atom abstraction of the parent phenolic compounds. The calculation of ionization potentials (IP V) of these antioxidants is another important parameter which provides hint towards the possible single electron transfer
(SET) mechanism of these compounds. Lower the value of ionization potential, higher is the probability of a particular compound to undergo single electron transfer resulting in the formation of ArOH•+. The calculated vertical ionization potential (IP V) values of all these phenolics are found to be highest in the gas phase and lowest in water medium. Similar IPV values are obtained with both 6-31+G(d) and 6-311++G(d,p) basis sets. The effect of high solvent polarity on lowering the ionization potential values were previously observed by Belcastro et. Al [36]. This implies that solvent polarity plays a crucial role in dictating the single electron transfer mechanism of an antioxidant. The polarity of the solvent has a significant effect on the IP V values of these compounds unlike BDE values where no such significant variation was observed. Like BDE values, increase in spacer length via amino substitution leads to decrease in IPV values of the phenolics, thereby, favoring single electron transfer.