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Structures, Energetics, and Spectra of (NH) and (OH)

Tautomers of 2-(2-Hydroxyphenyl)-1-azaazulene and its
Mercapto Analogue: A DFT/TDDFT Study
Journal: ACS Omega
Manuscript ID ao-2021-05045e
Manuscript Type: Article
Date Submitted by the

14-Sep-2021
Author:
Complete List of Authors: El-Meligy, Asmaa; Chemistry Department, Faculty of Science, Menoufia
University, Shebin El-Kom
El-Demerdash, Safinaz; Menoufia University faculty of science, chemistry
Abdel-Rahman, Mohamed; Chemistry Department, Faculty of Science,
Suez University, Suez, Egypt
Mahmoud, Mohamed A. M. ; Basic Sciences Department, Tanta Higher
Institute of Engineering and Technology, Tanta 31511, Egypt, chemistry
El-Nahas, Ahmed; Menoufia University, Department of Chemistry
ACS Paragon Plus Environment

Page 1 of 44 ACS Omega
1
2
3
4
Structures, Energetics, and Spectra of (NH) and (OH) Tautomers of 2-(2-
5
6
Hydroxyphenyl)-1-azaazulene and its Mercapto Analogue: A DFT/TDDFT
7
8
Study
9
Asmaa B. El-Meligy,a Safinaz H. El-Demerdash,a, Mohamed A. Abdel-Rahmanb, Mohamed A.
10
11 M. Mahmoudc, and Ahmed M. El-Nahasa,
aChemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom 32512, Egypt
12
13 bChemistry Department, Faculty of Science, Suez University, Suez, Egypt
14 cBasic Sciences Department, Tanta Higher Institute of Engineering and Technology, Tanta
15 31511, Egypt
16
17
18 ABSTRACT
19 The tautomerization of 2-(2-Hydroxyphenyl)-1-azaazulene (2HPhAZ) and its mercapto
20
analogue 2-(2-Mercaptophenyl)-1-azaazulene (2MPhAZ) in gas phase and in ethanol have been
21
22 studied using B3LYP and M06-2X density functional theory (DFT) with different basis sets.
23
24 Aromaticity, acidity and basicity were also calculated and compared with experimental data. In
25
26 addition, NMR, global descriptors, Fukui functions, NBO charges, and electrostatic potential
27 (ESP) of the investigated system have been discussed. The results reveal that the enol form of
28
29 2HPhAZ is thermodynamically and kinetically stable relative to the keto and rotamer forms in
30
31 the gas phase and ethanol. For 2MPhAZ, thiol is slightly more stable than thione in the gas phase.
32
33
However, in ethanol the stability order is reversed where the thione form is thermodynamically
34 and kinetically more stable relative to the thiol and rotamer forms at all used levels. Time-
35
36 dependent density functional theory-solvation model based on density (TDDFT-SMD)
37
38 calculations in acetonitrile have been utilized for simulation of UV-Vis electronic spectra.
39
40
41 Keywords:
42
43 Tautomers, 2-(2-Hydroxyphenyl)-1-azaazulene, mercapto analogue, B3LYP and M06-2X, UV
44
45 and NMR, Fukui functions, NBO and ESP.
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47
48
49
50
51 Corresponding authors:
52 amelnahas@hotmail.com (Ahmed M. El-Nahas)
53 hamdysafinaz@yahoo.com (Safinaz H. El-Demerdash)
54
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60 ACS Paragon Plus Environment
ACS Omega Page 2 of 44
1
2
3 INTRODUCTION
4
5 Azulene, an isomeric structure of naphthalene, has a fused five- and seven-membered
6
ring. 1,2 It has a blue color and high dipole moment.3–6 This non-benzenoid non alternant
7
8
9
structure attracts the interest of theoretical and experimental studies for its unusual photophysical
10 properties.7,8,17,9–16 Azulene derivatives have biological activities as well they can be anti-
11
12 inflammatory 18 or anti-cancer. 19
13
14 Azaazulenes, an azulene heterocyclic analogue, attracted the interest for their chemical,
15
physical properties and their biological activity20,21 as anticancer agents. 22 1-azaazulenes is the
16
17 most stable structure among the various structures of azaazulenes. 1-azaazulenes derivatives
18
19 have been used as ligands with metal ions.23–25 For example, 8-(diethylborylmethylamino)-3-
20
21 phenyl-1-azaazulene has been used as a bidentate ligand. 24
22 1-azaazulene with a phenol functional group at the 2-position has been synthesized by
23
24 Oda et al. 26 This structure is similar to 8-hydroxyquinoline which is an important chelating agent.
25
27,28 Thus, the 2-(2-Hydroxyphenyl)-1- azaazulene has the potential to be used as a chelating
26
27
28
ligand through imino nitrogen atom and phenolic oxygen atom. 2-(2-Hydroxyphenyl)-1-
29 azaazulene (2HPhAZ) has intense absorption in the visible region and its long-wavelength
30
31 absorption band shifts in the presence of several metal ions and, its emission upon excitation in
32
33 the presence of Pb2+, Al3+, and Sc3+ ions are 103 times higher than the quantum yield determined
34
in the absence of ions, which suggests potential sensing of these metal ions by 2HPhAZ. A
35
36 previous experimental study26 reported synthesis of 2-(2-Hydroxyphenyl)-1- azaazulene and its
37
38 X-ray crystallographic analysis, acidity, basicity, and its UV-Vis absorption and emission spectra.
39
40 This work uses quantum chemical calculations to investigate structures, stability and the
41 reactivity of tautomers and rotamer of 2HPhAZ and its mercapto analogue (2-(2-
42
43 Mercaptophenyl)-1- azaazulene; 2MPhAZ).
44
45 Tautomerism is a phenomenon of coexistence of two or more isomers of the same molecule.
46
Many types of tautomerization can be found depending on atom transfers. Our case study of
47
48 tautomerism includes the transfer of hydrogen atom from one position to another within the same
49
50 structure. In the system under consideration, such hydrogen transfer gives keto-enol tautomers.
51
52 The intramolecular hydrogen transfer between two equilibrium structures exhibits extreme
53 importance in pharmacology, organic chemistry, medicinal chemistry, and molecular biology.
54
55 29,30 Tautomers are formed by the exchange of hydrogen atoms between nitrogen and oxygen
56
57
58
59
1
2
3 atoms of the heterocyclic ring. The proton transfer and hydrogen bonding are important
4
5 characteristics of the hydrogen atom in chemistry. 2HPhAZ has hydroxyl substitution and
6
7 azaazulenyl ring. Therefore, equilibrium between enolimines (phenol-imine, OH-form) and
8
9
ketoenamines (C=O, NH-form) tautomeric form is expected (Scheme 1) that plays a critical role
10 in biosynthesis and medicinal chemistry. There is a lack of theoretical studies on 2HPhAZ.
11
12 Usually mercapto analogue shows a biological and pharmaceutical activity such as antioxidant
13
14 activity, antiviral Activity, Antiplatelet Agents and anti-mycobacterial activities.31–35 Therefore,
15
we proposed the mercapo analogue of 2HPhAZ to study the thiol-thione tautomerization.
16
17 In this work, we present a computational study on structures, relative stabilities and
18
19 electronic absorption spectra of tautomeric forms of 2HPhAZ and 2MPhAZ (Scheme 1) in the
20
21 gas phase and ethanol at the B3LYP/6-31G(d,p), B3LYP/6-311++G(2d,2p) and M06-2X/6-
22 311++G(2d,2p) levels of theory. 2HPhAZ is regarded as a potential ligand26 and its sensing
23
24 ability toward some metal ions has been reported.26 Similar to 2HPhAZ, 2MPhAZ also exhibit
25
26 tautomeric equilibrium between the thione and thiol forms. Two aspects here are important and
27
28
will be addressed, namely proton transfer and hydrogen bonding. A strong correlation exists
29 between aromaticity and structure/stability and, therefore, aromaticity of tautomers and rotamer
30
31 has also been examined in the light of Nucleus-Independent Chemical Shift (NICS) index. 36,37
32
33 Understanding physical and chemical properties of these tautomers may assist future
34
experimental studies on their potential use in some applications, particularly their ability to form
35
36 metal complexes for analytical and biological applications. Comparing obtained results with
37
38 experimental data26 might give important information concerning the origin of the observed
39
40 spectra and other properties.
41
42
43
44
45 N
46
N
47 HX H X
48
49 X=O enol keto
50 X=S thiol thione
51
52 Scheme 1: The tautomeric structure (enolimines/thiol and ketoenamines/thione form) of 2-(2-
53
54 Hydroxyphenyl)-1-azaazulene and its mercapto analogue.
55
56
57
58
59
1
2
3 2. COMPUTIANL METHOD
4
5 Tautomers, rotamer and transition states (TSs) for their interconversions were fully
6
7 optimized at the density functional theory of Becke’s three-parameter and Lee−Yang−Parr
8
9
hybrid functional (B3LYP)38–40 in conjunction with the 6-31G(d,p) ) basis set. Vibrational
10 frequency calculations have been conducted for each stationary point at the same level of
11
12 optimization to characterize its nature as minimum or transition state on the potential energy
13
14 surface of the relevant systems. TSs were confirmed by the presence of one imaginary frequency
15
that is examined using ChemCraft program.41 Minima show real frequencies. Minimum energy
16
17 path (MEP) was carried out at the level of optimization through intrinsic reaction coordinate
18
19 (IRC) 42,43 in order to verify that the located transition states connect the reactants and the desired
20
21 products. Energies were refined at B3LYP and meta hybrid generalized gradient approximation
22 (M06-2X) 44,45 functionals using 6-311++G(2d,2p) basis set at the B3LYP/6-31G(d,p) optimized
23
24 structures. Natural bond orbital (NBO) analysis46,47 has been performed at B3LYP/6-31G(d,p) to
25
26 compute the atomic charges, orbital interactions, and their impact on the structure and stability of
27
28
the investigated systems. Optimization has also been conducted in ethanol at B3LYP/6-31G(d,p)
29 using the solvation model based on density (SMD). 48 In addition, solvation effect in ethanol has
30
31 been calculated using M06-2X and B3LYP functionals with 6-311++G(2d,2p) basis sets at the
32
33 B3LYP/6-31G(d,p) optimized geometries. All calculations were performed using the Gaussian
34
09W program. 49
35
36 Nuclear magnetic resonance (NMR) spectroscopy is a helpful tool for tautomeric
37
38 equilibria study. NMR shielding was calculated using the gauge independent atomic orbital
39
40 (GIAO) method, 50–52 relative to the 13C and 1H isotropic chemical shielding of tetramethylsilane
41 (TMS), at the B3LYP/6-31G(d,p) optimized gas phase geometry in chloroform. These
42
43 calculations yield NICS36,37 index that is used to evaluate aromaticity, antiartomaticity and
44
45 nonaromaticity of each ring for the structures under consideration and the corresponding
46
transition states for their conversions. A ghost atom/probe (bq’s) has been located at the center
47
48 of the ring for determining NICS(0) and at 1 Å perpendicularly above the ring center for
49
50 determining NICS(1).36,37,53,54
51
52 To understand stability and reactivity of the studied structures, global chemical reactivity
53 descriptors55–58 have been determined using energies of highest occupied and lowest unoccupied
54
55 molecular orbitals (HOMO and LUMO). Accordingly, ionization potential (IP), electron affinity
56
57
58
59
1
2
3 (EA), absolute hardness (η), softness (S), electronegativity (X), chemical potential (μ),
4
5 electrophilicity index (ω) have been computed at B3LYP/ 6-31G(d, p) in the gas phase. The
6
7 global chemical reactivity descriptors have been calculated using the following equations:
8
9
IP = ― EHOMO
10 EA = ― ELUMO
11
12 η = (ELUMO - EHOMO) 2
13
14 S = 1 2η
15
16 χ = ―(ELIUMO + EHOMO) 2
17
18
μ = (ELUMO + EHOMO) 2
19
20 ω = μ2 2η
21 Fukui function is one of the density functional descriptors that is used to model chemical
22
23 reactivity and intramolecular site selectivity.[59] UCA-FUKUI program60 has been used to
24
25 calculate condensed Fukui functions (CFF) 𝑓+(𝑟 ), 𝑓−(𝑟 ), 𝑓0(𝑟 ) of studied structures by using
26
27 individual atomic charges purposed by Natural Population analysis (NPA). Fukui functions are
28 calculated using the following equations:
29
30 𝑓+(𝑟 ) = qr (N+1) -qr (N) for nucleophilic attack
31
32 𝑓−(𝑟 ) = qr (N) -qr (N-1) for electrophilic attack
33
34 𝑓0(𝑟 ) = qr (N+1) -qr (N-1) for radical attack
35 Where +, - and 0 denote the nucleophilic, electrophilic and radical attack, respectively.
36
37 Chattaraj et al. proposed the concept of generalized philicity[61] containing information about
38
39 known various global and local reactivity. The dual descriptor ∆f(r) is the difference between
40
41
nucleophilic and electrophilic attack in the Fukui function. If ∆f(r) is larger than zero at specific
42 site, this site will be favored for nucleophilic attack. Chemical reactivity toward positive and
43
44 negative charges can be also predicted through mapping electrostatic potential (ESP).
45
46 Electronic absorption spectra for the studied structures were calculated at TD-DFT-PBE
47 (TD-PBE)62,63 in acetonitrile using SMD approach at the B3LYP/6-31G(d,p) optimized gas phase
48
49 geometry. The Perdew, Burke, and Ernzerhof method (PBE0)[64] accurately estimated electron
50
51 excitations of most organic dyes.[65] However, for the molecule under consideration compared to
52
53
experimental results, it gives an underestimation of λmax by 59 nm whereas TD-PBE functional
54 overestimates and yields 11-13 nm difference depending on basis sets. GaussSum program66 was
55
56 used to simulate the ultraviolet-visible (UV-Vis) spectra.
57
58
59
1
2
3 3. RESAULTS AND DISCUSSION
4
5 3.1 Structural analysis
6
7 Gad et.al. 16 reported that B3LYP/6-31+G(d,p) produces the same order of stability obtained by
8
9
ab initio multi-levels CBS-QB3 method. Previous studies44,45,67,68 illustrated a high performance
10 of M06-2X functional in predicting trend of tautomers and conformers stability. Therefore, the
11
12 structures will be discussed at B3LYP/6-31G(d,p) and energies at B3LYP/6-31G(d,p), B3LYP/6-
13
14 311++G(2d,2p) and M06-2X/6-311++G(2d,2p) levels. Six isomers are discussed for 2HPhAZ
15
and 2MPhAZ. The optimized structures of these forms are collected in Figure 1. Reliable
16
17 structures are required in order to determine and rationalize the stability order of the investigated
18
19 system. To demonstrate the reliability of the obtained data, a comparison between theory and
20
21 experiment has to be established. Some geometrical parameters of 2HPhAZ optimized at
22 B3LYP/6-31G(d,p) compared with the recorded crystallographic X-ray data of 2HPhAZ26 are
23
24 listed in Table 1. A good agreement was observed with a mean absolute deviations (MADs) of
25
26 the calculated bond length of 0.010 Å in both gas phase and ethanol. The B3LYP/6-31G (d,p)
27
28
level nearly reproduces the structure as obtained from X-ray. This supports the reliability of this
29 level for structure optimization.
30
31 As illustrated in Figure 1, there are two tautomeric forms of 2HPhAZ and 2MPhAZ with an
32
33 intramolecular hydrogen bond (HB). The enol/thiol form shows an HB between the hydrogen
34
atom of the phenolic/thiophenolic group and the nitrogen atom of azaazulenyl moiety, phenol-
35
36 imine/thiophenol-imine HB, (O−H···N/S−H···N, 1.68/1.81 Å); see Scheme 1. This HB was
37
38 reported experimentally using 1H NMR.26 Keto exhibits a strong HB between oxygen atom of
39
40 carbonyl group and the hydrogen attached to the nitrogen atom of the five-membered ring in the
41 1-azaazulene (N−H···O, 1.55 Å). It is noteworthy that the short donor-acceptor atom distance in
42
43 both enol and keto forms give an indication about the existence of a low-barrier hydrogen bond
44
45 (LBHB). LBHB can be characterized by a short donor-acceptor distance that can be
46
approximately between 2.4 and 2.6 Å69–72 with a recorded biological importance.73 The donor
47
48 (O1)-acceptor (N1) distance is 2.59 Å in the investigated enol form and 2.49 Å in keto form. The
49
50 HB strength in the tautomeric structures can be predicted from their lengths. 69,74 As a result, the
51
52 keto form has the strongest H-bond. On the contrary, rotating the OH hydrogen atom to be far
53 from the acceptor atom (nitrogen atom) gives the corresponding rotamer with no hydrogen bond
54
55 and increases the donor-acceptor distance to 2.82 Å. Consequently, comparing the keto-enol and
56
57
58
59
1
2
3 the rotamer structural parameters may help in understanding their stability order; in particular the
4
5 keto-enol tautomers will be more stable than the rotamer.
6
7
8
9
10
11
12
13
14
15
16
17
18 Enol Thiol
19
20
21
22
23
24
25
26
27
28
29
30
31 Keto Thione
32
33
34
35
36
37
38
39
40
41
42
43 Rot. Thiol-Rot.
44 Figure1. Optimized structures of keto-enol tautomers and rotamer of 2HPhAZ as well as their
45
46 corresponding mercapto analogue at B3LYP/6-31G(d,p).
47
48
49
50 As displayed in Figure 1, the tautomeric form of 2MPhAZ have HB between the
51 hydrogen atom of the thiol group and the nitrogen atom of azaazulenyl moiety, (S−H···N, 1.81
52
53 Å). The thione form exhibits a slightly longer HB between sulfur atom and the hydrogen
54
55 attached to the nitrogen atom of the five-membered ring in the 1-azaazulene (N−H···S, 2 .02 Å).
56
57
58
59
1
2
3 Similar to hydroxyl compound, the mercapto analogues have donor (S1)-acceptor (N1) distance
4
5 of 3.02 Å in the investigated thiol form and 2.92 Å in the thione form with shorting of the bond
6
7 by 0.1 Å.
8
9
As depicted in Figure 1, enol/thiol structural parameters are significantly affected by the
10 ketonization and thionization processes. In case of 2HPhAZ, the migration of H atom from O to
11
12 N atom is accompanied by shortening of the N1-H, C2-C1' and C2'-O1 bonds by about 0.61,
13
14 0.04 and 0.07 Å, respectively. However, the N1-C2, C1'-C2' and O1-H1' bonds are elongated by
15
0.01, 0.04 and 0.55Å, respectively. While in case of 2MPhAZ, the migration of H1' atom from
16
17 S1 to N1 atom is accompanied by decreasing of the N1- H1', C2-C1' and C2'-S bonds by about
18
19 0.75, 0.04 and 0.04 Å, respectively. However, the N1-C2, C1'-C2' and S1- H1' bonds lengthen by
20
21 0.01, 0.3 and 0.5564 Å, respectively. Such structural changes in the keto/thione form affect
22 aromaticity of the five- and six-membered rings in the keto/thione tautomer by reducing the
23
24 intra-ring conjugation path. Due to the expected lower aromaticity of keto/thione than enol/thiol,
25
26 one can predict that ketonization/thionization of enol/thiol is accompanied by energetic
27
28
destabilization (as will be explained in the next Section).
29 The intramolecular proton transfer and rotation of the O-H and S-H bonds pass through
30
31 two transitions states TST and TSR for tautomerization and rotamerization, respectively. The
32
33 optimized structures of TST and TSR for 22HPhAZ and TST(SH) and TSR(SH) for 2MPhAZ at
34
B3LYP/6-31G(d,p) in the gas phase are presented in Fig. 1S. For TST of 2HPhAZ, the breaking
35
36 O–H bond stretches by 43.14% and the formed N–H bond elongated by 33.79% compared to
37
38 enol. With respect to the keto form, the breaking/forming, N–H/O-H bonds for TST are
39
40 elongated/shorten by 4.01/7.80%. Therefore, TST structure is similar to the structure of the keto
41 form rather than the enol form. According to the Hammond postulate,75 transformation of enol to
42
43 keto form is endothermic. The donor-acceptor distance in the TST falls between the
44
45 corresponding values in enol and keto. For TSR of 2HPhAZ, the rotated O-H bond length is
46
closer to O-H of rotamer and shorter than in enol by 0.03 Å. The H-O-C angle is rotated by 2.09º
47
48 from rotamer. The donor-acceptor distance in the TSR is stretched to 2.88 Å.
49
50 For TST(SH) of 2MPhAZ, the breaking S–H bond stretches by 14.57% and the formed N–
51
52 H bond is elongated by 25.35% compared to thiol. With respect to the thione form, the
53 breaking/forming, N–H/S-H bonds for TST are elongated/shorten by 25.84/21.88%. Therefore,
54
55 TST(SH) structure is similar to the structure of the thiol and thione forms. For TSR(SH) of 2MPhAZ,
56
57
58
59
1
2
3 the rotated S-H bond length is closer to S-H of rotamer and shorter than in enol by 0.03 Å. The
4
5 H-S-C angle is rotated by 3.37º from rotamer.
6
7
8
9
Table 1. Experimental X-ray and calculated bond lengthsa of 2HPhAZ and 2MPhAZ at
10 B3LYP/6-31G(d,p) in the gas phase and ethanol.
11
12 2HPhAZ 2MPhAZ
13
14 Exp(2HPhAZ). Gas phase Ethanol Gas phase Ethanol
15
16
N1–C2 1.365 1.369 1.370 1.364 1.367
17 C2–C3 1.401 1.415 1.409 1.418 1.413
18
19 C3–C3a 1.390 1.395 1.400 1.394 1.399
20
21 C3a–C4 1.388 1.404 1.404 1.403 1.404
22
C4–C5 1.378 1.388 1.389 1.389 1.389
23
24 C5–C6 1.394 1.405 1.404 1.405 1.405
25
26 C6–C7 1.382 1.393 1.395 1.393 1.395
27
28 C7–C8 1.386 1.399 1.398 1.399 1.398
29 C8–C8a 1.388 1.391 1.393 1.391 1.393
30
31 C8a–N1 1.353 1.349 1.353 1.349 1.354
32
33 C2–C1' 1.456 1.455 1.461 1.470 1.473
34
35
C1'–C2' 1.403 1.426 1.424 1.424 1.424
36 C2'–C3' 1.376 1.406 1.403 1.407 1.406
37
38 C3'–C4' 1.385 1.386 1.390 1.387 1.389
39
40 C4'–C5' 1.367 1.404 1.402 1.398 1.398
41
C5'–C6' 1.392 1.385 1.388 1.385 1.387
42
43 C6'–C1' 1.408 1.411 1.410 1.414 1.414
44
45 C2'–
46 1.353 1.341 1.352 1.779 1.787
47 O/S1'
48 a atom numbering is given in Figure. 1.
49
50
51
52
53
54
55
56
57
58
59
1
2
3 3.2. Energies and stability
4
5 Zero-point relative energies (ΔE0 ) for the keto, enol and rotamer 2HPhAZ and 2MPhAZ
6
7 structures in the gas phase and ethanol calculated at the B3LYP/6-31G(d,p), B3LYP/6-
8
9
311++G(2d,2p) and M06-2X/6-311++G(2d,2p) levels of theory, using B3LYP/6-31G(d,p)
10 optimized geometries, are presented in Table 2. For 2HPhAZ tautomerization, a slight deviation
11
12 in the values of ΔE0 obtained from triple zeta basis set, 6-311++G(2d,2p), than double zeta basis
13
14 set (6-31G(d,p)) with B3LYP (up to 0.2 kcal/mol) was noticed in the gas phase. The deviation
15
for rotamerization and calculated TSs has been found to be lower than 1.90 kcal/mol in the gas
16
17 phase and ethanol (see Table 2). Potential energy diagram for tautomerization and rotamerization
18
19 of 2HPhAZ at B3LYP/6-311++G(2d,2p) and M06-2X/6-311++G(2d,2p) in gas phase/ethanol is
20
21 illustrated in Figure 2a. Energy profiles for tautomerization and rotamerization from IRC
22 calculations at the B3LYP/6-31G(d, p) level are displayed in the supporting information (Figs.
23
24 2S and 3S). As displayed in Figures 2S, ketonization and rotamerization from enol are
25
26 endothermic which gives further support for the thermodynamic stability of enol. In the TST
27
28
(Figures 3S), the N1–H1 bond is formed gradually with the breaking of the O–H bond; the two
29 curves cross each other near the transition state (s = - 0.4 amu1/2 bohr). The double bond of C-O
30
31 and the single bond of N1-C2 are gently formed during the course of reaction. Fig. 2b shows the
32
33 potential energy diagram at B3LYP/6-31G(d,p) level.
34
On comparing ΔE0 for 2HPhAZ, the enol form is thermodynamically more stable than
35
36 the keto form by 6.80 (1.85) kcal/mol followed by the rotamer using the B3LYP/6-
37
38 311++G(2d,2p) method in the gas phase (ethanol) (Table 2 and Figure 2a). The relative stability
39
40 of the enol form is expected from the recorded slightly higher aromaticity of five and six-
41 membered rings where the NICS values relative to the keto form (as will be discussed in Section
42
43 3.4). In accordance with B3LYP results, the same stability order for keto and rotamer has been
44
45 observed at M06-2X. The M06-2X level provided higher energy differences between the enol
46
and keto structure 10.08 (4.89) kcal/mol in the gas phase (ethanol). The keto is slightly stable
47
48 than rotamer by 1.97 and 2.11 kcal/mol in the gas phase and ethanol solution, respectively, using
49
50 M06-2X functional. The rotamer form is higher in energy than keto by 6.43 and 6.33 kcal/mol at
51
52 B3LYP/6-311++G(2d,2p) in the gas phase and ethanol, respectively. The higher energy of
53 rotamerization than tautomerization has been previously reported 76 and thus, gives confidence
54
55 for the results of B3LYP level used in this study.
56
57
58
59
1
2
3 It is clear from Figure 1 that the HB distance in the keto at B3LYP is shorter than enol.
4
5 Matching with B3LYP level, the HB distance of enol (N…H =1.68 Å) is larger than the HB
6
7 distance of keto (O….H=1.55 Å) at the M06-2X level. For both two levels of calculation, the
8
9
enol is more stable thermodynamically.
10 Table 2 listed zero point energy barriers for the tautomerization and rotamerization of
11
12 2HPhAZ. From the calculated barrier heights, it can be noticed that HB plays a vital role in the
13
14 kinetic stability of enol form in accordance with the results obtained by Garcia-viloca et. al. for
15
Maleate Anion.77 The barrier from keto to enol over TST equals - 0.90 and -1.41 kcal/mol in the
16
17 gas phase at B3LYP/6-311++G(2d,2p) and M06-2X/6-311++G(2d,2p), respectively. Garcia-
18
19 viloca et al. 77 reported an energy barrier of -0.85 kcal/mol for the intramolecular proton transfer
20
21 in the Maleic Monoanion calculated at MP2/6-31+G (d,p) in the gas phase.
22 For 2MPhAZ, the thiol form is thermodynamically more stable than the thione form by 0.34,
23
24 1.21 and 2.89 kcal/mol followed by the thiol rotamer 0.94, 1.92 and 2.77 kcal/mol using
25
26 B3LYP/6-31G(d,p), B3LYP/6-311++G(2d,2p) and M06-2X/6-311++G(2d,2p) levels in the gas
27
28
phase (Table 2 and Fig. 2c). In contrast to gas phase, the higher stability of thione form than thiol
29 and its rotamer in ethanol has been observed at all levels of calculations. The thione is highly
30
31 stable relative to thiol/its rotamer by 5.36/7.77, 4.84/6.10 and 4.35/4.27 kcal/mol at B3LYP/6-
32
33 31G(d,p), B3LYP/6-311++G(2d,2p) and M06-2X/6-311++G(2d,2p) levels, respectively, in
34
ethanol (Table 2 and Figure 2d). The stability order of thiol-thione tautomers of 2MPhAZ agrees
35
36 with the predominance of 2-pyridinethione (thione form) over 2-pyridinethiol (thiol form) in
37
38 polar solvents.78 The thiol-rotamer is higher in energy than its thiol form by 1.26 and 0.08
39
40 kcal/mol at B3LYP/6-311++G(2d,2p) and M06-2X/6-311++G(2d,2p) in ethanol, respectively.
41 Determination of equilibrium constants depends on Gibbs free energies (ΔG) for the
42
43 ―∆𝐺 𝑅𝑇)
investigated tautomers/rotamers according to 𝐾 = 𝑒( relation, where K is the equilibrium
44
45 constant, R is the universal gas constant, and T is the temperature in Kelvin. Relative Gibbs free
46
47 energies (ΔG298, 𝛥𝐺#298) calculated at the B3LYP/6-31G(d,p), B3LYP/6-311++G(2d,2p) and
48
49
M06-2X/6-311++G(2d,2p) levels of theory are collected in Table 3. The values of ΔG298 give the
50 same order of stability for investigated tautomers/rotamers as relative zero-point energies. For
51
52 2HPhAZ, 𝛥𝐸0, 𝛥𝐸#0, 𝛥𝐺298 and 𝛥𝐺#298 in ethanol calculated at B3LYP and M06-2X levels
53
54 (Tables 2 and 3) produce the same order of stability observed in the gas-phase. However, a
55
56
57
58
59
1
2
3 different stability order was observed in ethanol for 2MPhAZ at all levels of calculations (Tables
4
5 2 and 3).
6
7 It can be noticed that the energy differences in ethanol are higher than the corresponding
8
9
results in the gas-phase. This observation can be attributed to the higher dipole moments of keto
10 and thione tautomers in the gas phase which further increase in ethanol. The dipole moments of
11
12 the studied tautomers/rotamers in the gas phase and in ethanol calculated at the B3LYP/6-
13
14 31G(d,p), B3LYP /6-311++G(2d,2p) and M06-2X/6-311++G(2d,2p) levels of theory are given in
15
Table 4. The keto form has the highest polarity in the gas-phase/ethanol (B3LYP/6-
16
17 311++G(2d,2p):6.24/12.67 Debye) with the highest difference in the dipole moments between
18
19 the two phases (about 6 Debye), followed by the enol form (B3LYP/6-311++G(2d,2p):4.30/7.30
20
21 Debye). The rotamer has the lowest dipole moment value (B3LYP/311++G(2d,2p): 1.06/2.49
22 Debye). TST and TSR have dipole moment between the corresponding equilibrium structures.
23
24 The thione form has the highest polarity in the gas-phase/ethanol (B3LYP/6-
25
26 311++G(2d,2p):7.85/15.04 Debye) with the highest difference in the dipole moments between
27
28
the two phases (about 7 Debye), followed by the thiol form (B3LYP/6-311++G(2d,2p):4.35/7.50
29 Debye). The thiol-rotamer has the lowest dipole moment value (B3LYP/311++G(2d,2p):
30
31 2.37/4.13 Debye).
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
1
2
3 a) b)
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26 c) d)
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
Figure2. Potential energy diagram (𝛥𝐸0,𝛥𝐸0‡ , kcal/mol) for tautomerization and rotamerization
48
49 of 2HPhAZ at B3LYP/6-31G(d,p) (bold), B3LYP/6-311++G(2d,2p) (italic) and M06-2X/6-
50
51 311++G(2d,2p) (underline), in the gas phase/ethanol (a,b) and their corresponding mercapto
52
53 analogue in the gas phase (c) and ethanol using SMD solvation model (d).
54
55
56
57
58
59
1
2
3 Table 2. Relative zero-point energies (ΔE0, 𝛥𝐸0‡ , kcal/mol) for tautomers and rotamers of
4
5 2HPhAZ and 2MPhAZ in kcal/mol, in the gas phase and ethanol at the B3LYP/6-31G(d,p),
6
7 B3LYP/6-311++G(2d,2p) and M06-2X/6-311++G(2d,2p) levels of theory.
8
9 ΔE0 (Gas-phase) ΔE0 (Ethanol)
10 2HPhAZ/2MPhAZ
11
B3LYP B3LYPa M06-Xa B3LYP B3LYPa M06-2Xa
12
Enol 0.00 0.00 0.00 0.00 0.00 0.00
13
14 Keto 6.83 6.80 10.08 3.18 1.85 4.89
15
16 Rotamer 14.85 13.24 12.04 9.72 8.18 6.99
17
18 TST 5.72 5.90 8.67 2.15 2.02 3.53
19
20 TSR 16.53 14.65 13.17 12.64 10.98 9.52
21
22
Thiol 0.00 0.00 0.00 5.36 4.84 4.35
23 Thione 0.34 1.21 2.89 0.00 0.00 0.00
24
25 Thiol-Rot. 2.77 1.92 0.94 7.77 6.10 4.27
26
27 TST(SH) 0.61 1.49 2.09 11.15 4.39 4.12
28
29 TSR(SH) 7.55 5.85 4.38 18.83 9.52 7.58
30 a Method
31 /6-311++G(2d,2p)// B3LYP/6-31G(d,p)
32
33
‡
34 Table 3. Relative Gibbs free energies (ΔG298) and Gibbs Free Energy Barrier (𝛥𝐺298 ) for
35
36 tautomers and rotamers of 2HPhAZ and 2MPhAZ, in kcal/mol, in the gas-phase and under the
37
38 effect of ethanol calculated at the B3LYP/6-31G(d,p), B3LYP /6-311++G(2d,2p) and M06-
39 2X/6-311++G(2d,2p) levels of theory.
40
41 ΔG298 (Gas-phase) ΔG298 (Ethanol)
42
43 2HPhAZ/2MPhAZ M06-
44 B3LYP B3LYPa B3LYP B3LYPa M06-2Xa
2Xa
45
46 Enol 0.00 0.00 0.00 0.00 0.00 0.00
47
48 Keto 6.84 6.81 10.09 3.20 1.88 4.91
49
50 Rotamer 14.30 12.69 11.49 9.45 7.91 6.72
51
TST 6.07 6.25 9.02 2.45 2.31 3.82
52
53 TSR 16.10 14.31 12.83 12.36 10.70 9.23
54
55 Thiol 0.00 0.00 0.00 6.12 5.60 5.12
56
57
58
59
1
2
3 Thione 0.80 1.66 3.34 0.00 0.00 0.00
4
5 Thiol-Rot. 2.56 1.71 0.73 9.06 7.39 5.56
6
7 TST (SH) 1.17 2.05 2.65 12.68 5.92 5.65
8
9 TSR(SH) 7.54 3.92 2.41 19.92 10.61 8.67
10 a Method/6-311++G(2d,2p)//B3LYP/6-31G(d,p)
11
12
13
14 Table 4. Dipole moments (in Debye) in the gas-phase and ethanol for tautomers and rotamers of
15
16 of 2HPhAZ and 2MPhAZ calculated at the B3LYP/6-31G(d,p),B3LYP /6-311++G(2d,2p) and
17
18
M06-2X/6-311++G(2d,2p) levels of theory.
19 Gas phase Ethanol
20 2HPhAZ/2MPhAZ
21 B3LYP B3LYPa M06-2X B3LYP B3LYPa M06-2X
22
23 Enol 4.29 4.30 4.69 7.12 7.30 7.74
24
25 Keto 6.02 6.24 6.79 11.98 12.67 13.47
26
27 Rotamer 0.96 1.06 1.20 2.16 2.49 2.75
28
29
TST 5.90 6.09 6.64 10.18 10.58 11.21
30 TSR 1.63 1.74 1.94 3.61 3.92 4.20
31
32 Thiol 4.65 4.35 4.67 7.74 7.50 7.86
33
34 Thione 7.92 7.85 8.71 14.81 15.04 16.00
35
36 Thiol-Rot. 2.41 2.37 2.53 4.01 4.13 4.31
37
38 TST(SH) 6.59 6.33 6.93 10.09 9.24 9.70
39 TSR(SH)
40 2.25 1.82 2.06 3.55 4.46 4.63
41 a Method/6-311++G(2d,2p)//B3LYP/6-31G(d,p)
42
43
44
45 3.3. NMR analysis
46
LBHB can be investigated by NMR calculation. 79–81 In the NMR spectrum, the appearance
47
48 of a low-field proton signal (high chemical shifts) is a well-known effect of forming a hydrogen
49
50 bond with a sign for an LBHB. Detailed data about NMR in enol, keto and rotamer and their
51
52 mercapto analogue at B3LYP/6-31G(d,p) in comparison between experimental NMR parameters
53 are summarized in Table 5. The calculated 13C and 1H NMR chemical shifts for 2HPhAZ in
54
55 CHCl3 show good agreement with the experimental findings. Plotting of calculated 13C and 1H
56
57
58
59
1
2
3 NMR chemical shifts against experimental values of 2HPhAZ is displayed in Figure 3. A high
4
5 correlation between calculated and experimental results of enol form was noticed which gives
6
7 confidence on the used computational procedures. From Table 5, C2' in the keto/thione form has
8
9
the highest chemical shift (171.33/173.80 ppm) that can be attributed to its closeness to the
10 oxygen/sulfur atom of the carbonyl/thioketone group. Apparently, H1 of the keto/thione form has
11
12 the highest chemical shift (19.40/18.44 ppm) that accompanies the formation of strong LBHB
13
14 (N1-H1…O1/S1= C2'), followed by H1 of the enol/thiol form (14.76/13.58 ppm). On contrary, H1
15
of the rotamer/thiol-rotamer has the lowest chemical shift (4.51/4.02 ppm). The calculated 1H
16
17 NMR chemical shifts for LBHB reveal an agreement, to some extent, with those reported by
18
19 Hibbert and Emsley82 for a proton chemical shifts of to be as far as 20 ppm (relative to TMS).
20
21 Therefore, the calculated 1H NMR chemical shifts help in predicting presence or absence of HB
22 and distinguish LBHB.
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
1
2
3 Table 5. 13C and 1H NMR chemical shifts (in ppm) calculated at the B3LYP/6-31G(d,p) level of
4
5 theory for of 2HPhAZ and 2MPhAZ using the GIAO method in CHCl3.
6
7 Enol Exp. Keto Rot. Thiol Thione Rot.(SH)
8 13C chemical shifts
9 C2 162.75 167.00 156.25 164.82 163.36 155.18 161.82
10
11
C3 104.25 109.40 101.21 108.51 106.79 104.01 105.72
12 C4 130.51 134.70 128.62 129.31 130.64 130.67 130.46
13 C5 125.62 129.50 128.44 123.59 125.17 128.89 124.26
14 C6 132.04 136.50 129.69 131.38 132.54 132.67 132.11
15 C7 126.22 130.20 129.18 124.16 125.69 129.57 124.92
16
17 C8 128.53 133.70 118.29 130.98 129.56 121.34 130.91
18 C3a 141.87 146.20 139.18 142.49 140.64 137.69 142.48
19 C8a 150.37 156.00 143.42 153.35 149.80 142.05 151.50
20 C1' 115.13 117.70 109.98 121.04 124.53 120.66 127.59
21
C2' 157.64 160.30 171.33 150.67 143.35 173.80 139.85
22
23 C3' 113.51 118.00 119.38 111.62 127.31 135.12 127.46
24 C4' 127.59 132.10 129.82 125.40 123.94 123.57 124.03
25 C5' 113.67 119.00 108.40 115.19 118.53 115.09 119.69
26 C6' 124.81 128.40 124.55 128.62 126.84 126.65 125.94
27 1H
28 chemical shifts
29 H3 7.83 7.70 7.16 7.68 7.96 7.44 7.97
30 H4 8.62 8.49 8.07 8.61 8.62 8.27 8.65
31 H5 7.88 7.63 7.64 7.80 7.86 7.83 7.83
32
H6 8.11 7.78 7.69 8.09 8.13 7.95 8.12
33
34 H7 7.96 7.73 7.67 7.91 7.95 7.86 7.96
35 H8 8.43 8.55 7.72 8.52 8.47 8.02 8.66
36 H1-O(S)/N 14.76 14.22 19.40 4.51 13.58 18.44 4.02
37 H3' 7.03 7.10 6.65 6.74 7.42 7.66 7.24
38
H4' 7.43 7.35 7.25 7.38 7.28 7.02 7.24
39
40 H5' 7.01 6.96 6.43 7.12 7.22 6.86 7.30
41 H6' 8.11 7.94 7.66 7.87 8.35 7.93 8.34
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
1
2
3
4 180
5
160
6
7 140
8 120
9
Experimental
100 2
R =0.999
10
80
11
12 60
13 40
14 20
15
0
16
17 0 20 40 60 80 100 120 140 160 180
18 Calculated
19
20
21 Figure 3. Plot of the experimental chemical shifts verses the calculated 13C and 1H NMR
22
23 chemical shifts at the B3LYP/6-31G(d,p) level of theory 2HPhAZ using the GIAO method in
24
25
CHCl3
26
27
28 3.4. Aromaticity (NICS index)
29
30 Since Hückel rule is not sufficiently strong to predict the aromaticity of complex cyclic
31
delocalized systems, some other indices has been developed to determine aromaticity such
32
33 Nucleus Independent Chemical Shifts (NICS).37 NICS is based on the negative value of magnetic
34
35 shielding. Although NICS index is somewhat sensitive to basis set, previous studies37,83
36
37 calculated NICS as single point at B3LYP/6-31G(d,p) with a reasonable accuracy. For the
38 investigated systems and their corresponding TSs, four NICS calculations were performed at the
39
40 B3LYP/6-31G(d,p) level in the chloroform to evaluate the aromatic character of each ring are
41
42 presented in Table 6 and Table1S, respectively. NICSiso(0) refers to the isotropic shielding at the
43
44
center of the ring, NICS(0)zz, the ZZ contribution evaluated at the center of the ring, as well as
45 NICSiso(1) and NICSzz(1) which are analogue indices computed at 1 Å above the center of the
46
47 ring. NICS values for pyrrole, benzene, cycloheptatriene (C7H8), azulene37 and azaazulene84 are
48
49 also given in Table 6 for comparison. The more negative the NICS values the more aromaticity
50
of the ring. According to previous studies, 37,76,84 the five-membered ring is more aromatic than
51
52 the six- followed by the seven-membered ring. As can be seen from Table 6, the pyrrole ring is
53
54 more aromatic than benzene and the aromaticity is less in C7H8. Apparently, the NICS results in
55
56 Table 6 provided a good reproduction of NICSiso(0) of previous studies of benzene, pyrrole,
57
58
59
1
2
3 azulene37,76 and azaazulene84 and also can support order of stability. The enol/thiol form has
4
5 strong aromatic character in five, six and seven membered rings. By ketonization, these rings
6
7 recorded lower negative NICS values. Thus, the enol/thiol form is more aromatic than its
8
9
keto/thione tautomer. The aromaticity of the quasi HB ring in the keto/thione and enol/thiol
10 forms is also determined. These rings exhibit antiaromatic character based on their positive
11
12 NICSiso(x) values. The antiaromatic character of the HB ring in enol/thiol is larger than in the
13
14 keto/thione form. This implies that the magnetic shielding feature of the enol and keto or thiol
15
and thione tautomers can be a good tool to express the energetic stabilization of enol/thiol than
16
17 keto/thione and the kinetic and thermodynamic stability of the enol/thiol structure. However, it is
18
19 still not enough to explain the instability of the rotamer and the stability of thione in ethanol. The
20
21 larger negativity of NICS index of the rotamer indicates the absence of the intramolecular H-
22 bond and thus the aromaticity of its rings. An insight into NICS values of the TST, TSR and their
23
24 mercapto analogue (Table 1S) reveals that the TSs have intermediate aromatic character between
25
26 their reactant and product.
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
1
2
3 Table 6. NICS (in ppm) of the tautomers and rotamers calculated at B3LYP/6-31G(d,p). Five-
4
5 and seven-membered rings of azaazulene and phenyl ring as presented in Figure.1.
6
7 Compound NICS(0)iso NICS(0)zz NICS(1)iso NICS(1)zz
8 Benzene -9.71(-11.5)a -14.15 -11.32 -29.20
9
10 Pyrrole -15.81(-17.3) a -20.56 -11.74 -30.63
11
12 C7H8 -4.28 -7.05 -4.70 -11.61
13 Five-membered ring -19.28 (-21.5)a(-18.1)b -32.76 -17.24 -46.64
14 Azulene
15 Seven-membered ring -6.88 (-8.3)a(-5.5)b -9.93 -8.81 -22.38
16
Five-membered ring -16.72 ( -15.0)b -27.27 -17.21 -44.53
17 Aza-Azulene
18 Seven-membered ring -7.99 (-6.9)b -14.65 -9.77 -24.58
19
20 Enol-form Five-membered ring -14.32 -18.81 -15.08 -37.59
21
Seven-membered ring -6.87 -10.61 -8.65 -21.86
22
23 Six-membered ring -8.28 -10.72 -9.08 -20.67
24
25 HB-ring +2.92 -14.38 +0.36 -4.42
26 Keto-form Five-membered ring -12.64 -21.97 -12.09 -28.60
27
28 Seven-membered ring -4.64 -5.70 -6.75 -15.62
29
31 HB-ring +1.77 -13.46 -0.70 -4.84
32
33 Rotamer Five-membered ring -14.50 -20.87 -15.63 -40.00
34
Seven-membered ring -7.16 -11.80 -8.85 -22.90
35
37
38 Thiol-form Five-membered ring -14.95 -10.89 -16.39 -38.60
40
42
43 HB-ring +2.14 +25.89 -0.27 7.42
44 Thione-form Five-membered ring -13.50 -22.32 -11.99 -28.74
45
47
Six-membered ring -5.10 -9.00 -7.50 -16.53
48
49 HB-ring +0.99 +25.35 -0.95 +5.27
50
51 Thiol-Rot. Five-membered ring -14.79 -18.98 -15.23 -38.37
53
55
aref [37] at B3LYP/6-31G(d,p) using GIAO; bref [83] at B3LYP/6-31+G(d,p) using GIAO.
56
57
58
59
1
2
3
4
5
. DFT reactivity descriptors and Fukui function
6 Chemical reactions involve some charge transfer between reactant parts of molecules.
7
8 Therefore local properties are key properties in reactivity orientated description of molecular
9
10 systems. The IP represents the ability to donate an electron, while the EA illustrates the ability to
11
accept an electron. Table 7 lists the energies of HOMO, LUMO, energy gap (Eg), vertical IP and
12
13 EA as well as 𝜂,𝑆, 𝜒, 𝜇, and 𝜔. From Table 7, it has been found that keto/thione form has the
14
15 lowest HOMO-LUMO gap (2.55/1.87 eV) followed by enol/thiol forms (3.08/2.98 eV). The
16
17 rotamer/thiol-rotamer have the highest gap (3.47/3.24 eV). It is well known that the lower the
18 energy gaps the higher the reactivity of the molecule. 85,86 Thus, the keto/thione form is expected
19
20 to have high chemical reactivity, low hardness and high softness than enol/thiol and their rotamer.
21
22 The keto/thione form can act as electron donor and electron acceptor by having the highest
23
24
HOMO energy (EHOMO = -4.85/-4.70 eV; the lowest value of the IP) and the lowest LUMO
25 energy (ELUMO = -2.55/-2.83 eV; largest value of the affinity. But from the calculated ω and 𝜂
26
27 they are better to act as strong electrophiles. The good electrophile should have high chemical
28
29 potential and low hardness.60 The enol /thiol form shows the highest electronegativity value (χ =
30
3.92/3.93 eV) and the most negative chemical potential, so they will be the best electron acceptor.
31
32 One of the most fundamental questions of the chemical reactivity is to determine the most
33
34 favorable place to add or remove electron to molecule. Electron density distributions are basic to
35
36 understand the electrophilic and nucleophilic attacks. The calculated condensed Fukui function
37 value for enol/thiol and keto/thione forms are shown in Table 8 and 9 and for rotamers are given
38
39 in the supporting information.
40
41 Table 7. Global chemical descriptor (eV) of the studied structures at B3LYP/6-31G(d,p) in the
42 gas phase.
43
44 EHOMO ELUMO Eg IP EA χ η S μ Ω
45
46 Enol -5.46 -2.38 3.08 5.46 2.38 3.92 1.54 0.33 -3.92 4.99
47 Keto -4.85 -2.55 2.30 4.85 2.55 3.70 1.15 0.43 -3.70 5.94
48 Rotamer -5.51 -2.04 3.47 5.51 2.04 3.77 1.74 0.29 -3.77 4.10
49
50
Thiol -5.42 -2.44 2.98 5.42 2.44 3.93 1.49 0.34 -3.93 5.19
51 Thione -4.70 -2.83 1.87 4.70 2.83 3.77 0.93 0.54 -3.77 7.61
52 Thiol-Rot. -5.49 -2.25 3.24 5.49 2.25 3.87 1.62 0.31 -3.87 4.62
53
54
55
56
57
58
59
1
2
3 From the values reported in Table 8, the electrophilic attack order for enol in gas phase is C6
4
5 > N1 > C4' > C5 >C7> C4 > C3 > C2. The C6 and N1 atoms show higher f-- value indicating the
6
7 possible sites of electron acceptor. Note that the positions of reactive electrophilic sites are
8
9
mainly located on the azazulene ring. On the other hand, for the nucleophilic attack, the
10 reactivity order is C6 > C8 > C4 > C5' > C4'. According to the dual descriptor (∆f) > 0 value for
11
12 N1 and O1, these sites are favoured for nucleophilic attack. Among all hydrogen atoms H1 is
13
14 highly nucleophilic and H6 is highly electrophilic.
15
For keto form, the C6, C8, C4, C1', N1, C5, C3, and C7 atoms are more susceptible sites
16
17 for accepting electrons and C6, C4,C7, C5, C8a, C3a, C2, and C8, atoms are the most favorable
18
19 sites for electron donation. Thus, heterocyclic ring is most reactive sites for electron donor-
20
21 acceptor interactions. The C2, N1 atoms are highly positive for dual descriptor (∆f) value that
22 makes its tendency to donate electrons. According to highly negativity dual descriptor (∆f), the
23
24 C2' and C8 atoms are the most favorable sites for accepting electrons. In both enol and keto
25
26 forms, the C6 atom is suitable site for both electrophilic and nucleophilic attacks by having the
27
28
highest values of f - and f +.
29 In cases of rotamer form it is observed that C7, C5, C2, C3, C4 and C6 atoms have higher
30
31 f-- value, which shows the possible site for electrophilic attack and C6, C1', C8, C5' and C4 have
32
33 higher f+ value which indicates the possible site for nucleophilic attack. The dual descriptor (∆f)
34
value of C2', C1' and C6 founded are highly positive, that has the tendency to donate electrons.
35
36 On contrary, N1 and O1 are susceptible to acquire electrons.
37
38 Table 9 shows that at the DFT level the most susceptible site to a nucleophilic attack for thiol is
39
40 located on C6. In the case of an electrophilic attack, the most reactive site are on C5’ and C6,
41 respectively. For a free radical attack the most reactive site is on C6. While for the thione, C6
42
43 implies that this will be preferred site for the electrophilic and free radical attacks, while an
44
45 nucleophilic attack is more probable on H1’ and C7, respectively. Thiol Rot (Table 9) show that
46
the most favourite sites to nucleophilic and free radical attacks are C6 while C7and C5 will be
47
48 preferred sites for the electrophilic attack, respectively. In Table 9 our results reported that a
49
50 preferred site for nucleophilic and electrophilic attack is C6 in all tautomers forms.
51
52
53
54
55
56
57
58
59
1
2
3 Table 8. Condensed Fukui functions (fk+, fk-, fk0) and dual-descriptor (Δfk) evaluated from
4
5
Natural Population Analysis for Enol and Keto forms at B3LYP/6-31G(d,p).
6
Enol Keto
7
8 Za fk - fk + fk 0 ( Δfk) Za fk - fk + fk 0 ( ∆fk)
9 N1 0.0374 -0.0937 0.0282 0.0563 N1 0.0239 -0.0802 0.0282 0.0563
10
11 C2 0.0222 0.0067 0.0144 -0.0155 C2 0.0013 0.0276 0.0144 0.0264
12
C3 0.0258 0.0159 0.0208 -0.0100 C3 0.0188 0.0229 0.0208 0.0041
13
14 0.0327 0.0563 0.0445 0.0236 C4 0.0461 0.0428 0.0445 -0.0033
15
C4
16 C5 0.0348 0.0163 0.0255 -0.0185 C5 0.0207 0.0304 0.0255 0.0097
17
18 C6 0.0406 0.0694 0.0550 0.0288 C6 0.0595 0.0506 0.0550 -0.0089
19
20 C7 0.0333 0.0123 0.0228 -0.0210 C7 0.0118 0.0339 0.0228 0.0221
21 0.0077 0.0564 0.0320 0.0487 C8 0.0499 0.0142 0.0320 -0.0357
22 C8
23 H3 0.0250 0.0233 0.0242 -0.0017 H3 0.0172 0.0311 0.0242 0.0139
24
25 H4 0.0239 0.0246 0.0242 0.0007 H4 0.0213 0.0272 0.0242 0.0059
26
27 H5 0.0267 0.0277 0.0272 0.0010 H5 0.0247 0.0297 0.0272 0.0049
28 0.0268 0.0281 0.0274 0.0013 H6 0.0249 0.0300 0.0274 0.0051
29 H6
30 0.0256 0.0266 0.0261 0.0011 H7 0.0232 0.0289 0.0261 0.0057
H7
31
32 C3a 0.0203 0.0197 0.0200 -0.0006 C3a 0.0147 0.0254 0.0200 0.0107
33
34 C8a 0.0046 0.0120 0.0083 0.0074 C8a -0.0128 0.0294 0.0083 0.0166
35
C1' 0.0093 0.0285 0.0189 0.0192 C1' 0.0425 -0.0047 0.0189 -0.0378
36
37 -0.0174 -0.0567 0.0370 0.0393 C2' -0.0706 -0.0035 0.0370 -0.0672
38
C2'
39 C3' -0.0099 0.0292 0.0096 0.0193 C3' 0.0002 0.0190 0.0096 0.0188
40
41 C4' 0.0361 0.0367 0.0364 0.0005 C4' 0.0350 0.0378 0.0364 0.0029
42
C5' 0.0300 0.0516 0.0408 0.0215 C5' 0.0399 0.0417 0.0408 0.0017
43
44 0.0220 0.0156 0.0188 -0.0063 C6' 0.0264 0.0112 0.0188 -0.0152
45 C6'
46 H4' 0.0250 0.0316 0.0283 0.0066 H4' 0.0283 0.0283 0.0283 0.0000
47
48 H5' 0.0253 0.0295 0.0274 0.0042 H5' 0.0281 0.0267 0.0274 -0.0014
49
50 H6' 0.0156 0.0229 0.0193 0.0073 H6' 0.0203 0.0183 0.0193 -0.002
51 -0.0194 -0.0576 0.0385 0.0382 O1 -0.0319 -0.0452 0.0385 0.0134
52 O1
53 0.0031 0.5219 0.2625 0.5188 H1 0.0388 0.4862 0.2625 0.4474
H1
54
55
aatom numbering is given in Figure 1.
56
57
58
59
1
2
3 Table 9. Condensed Fukui functions (fk+, fk-, fk0) and dual-descriptor (Δfk) evaluated from
4
5 Natural Population Analysis for Thiol and Thione forms at B3LYP/6-31G(d,p).
6
7 Thiol Thione
8 Za fk - fk+ fk 0 ( Δfk) Za fk - fk+ fk 0 ( ∆fk)
9
N1 0.0056 -0.0776 0.0360 0.0720 N1 0.0105 -0.0825 0.0360 0.0720
10
11 0.0190 -0.0123 0.0034 -0.0068 -0.0057 0.0125 0.0034 0.0068
12 C2 C2
13 C3 0.0274 0.0186 0.0230 -0.0088 C3 0.0143 0.0317 0.0230 0.0174
14
15 C4 0.0320 0.0479 0.0400 0.0159 C4 0.0418 0.0382 0.0400 -0.0036
16
17 C5 0.0382 0.0152 0.0267 -0.0230 C5 0.0225 0.0310 0.0267 0.0085
18
19 C6 0.0403 0.0543 0.0473 0.0141 C6 0.0554 0.0392 0.0473 -0.0162
20 0.0378 0.0162 0.0270 -0.0216 0.0133 0.0407 0.0270 0.0274
21 C7 C7
22 0.0056 0.0363 0.0210 0.0307 0.0458 -0.0038 0.0210 -0.0420
C8 C8
23
24 H3 0.0281 0.0136 0.0209 -0.0145 H3 0.0193 0.0225 0.0209 0.0032
25
26 H4 0.0250 0.0207 0.0229 -0.0043 H4 0.0207 0.0250 0.0229 0.0043
27
28 H5 0.0278 0.0243 0.0261 -0.0035 H5 0.0241 0.0281 0.0261 0.0040
29
H6 0.0279 0.0246 0.0263 -0.0033 H6 0.0242 0.0283 0.0263 0.0041
30
31 0.0271 0.0229 0.0250 -0.0042 0.0225 0.0275 0.0250 0.0050
32
H7 H7
33 C3a 0.0233 0.0098 0.0166 -0.0135 C3a 0.0175 0.0156 0.0166 -0.0019
34
35 C8a 0.0098 0.0163 0.0130 0.0066 C8a -0.0104 0.0365 0.0130 0.0261
36
37 C1' 0.0004 0.0120 0.0062 0.0116 C1' 0.0312 -0.0188 0.0062 -0.0124
38
39 C2' 0.0246 0.0137 0.0191 -0.0110 C2' 0.0184 0.0199 0.0191 0.0015
40 0.0312 0.0038 0.0175 -0.0274 0.0226 0.0124 0.0175 -0.0102
41 C3' C3'
42 0.0252 0.0343 0.0297 0.0091 0.0221 0.0374 0.0297 0.0154
C4' C4'
43
44 C5' 0.0429 0.0468 0.0449 0.0040 C5' 0.0526 0.0371 0.0449 -0.0155
45
46 C6' 0.0125 0.0221 0.0173 0.0096 C6' 0.0126 0.0220 0.0173 0.0094
47
48 H5' 0.0243 0.0273 0.0258 0.0030 H5' 0.0263 0.0253 0.0258 -0.0010
49 0.0145 0.0157 0.0151 0.0011 0.0214 0.0088 0.0151 -0.0126
50 H6' H6'
51 -0.0153 0.0183 0.0015 0.0030 -0.0046 0.0076 0.0015 0.0030
52
S1 S1
53 H1 -0.0106 0.3466 0.1680 0.3360 H1 0.2455 0.0905 0.1680 -0.1550
54
55
56
57
58
59
1
2
3
4
5 3.6. Charge distribution and ESP analysis
6
7 The charge distribution and electrostatic potential (ESP) surface are widely used to
8
9
determine the reactivity of a given molecule and its expected interaction with other systems.
10 NBO charges of the investigated structures have been calculated in the gas-phase at the
11
12 B3LYP/6-31G (d,p) level and are collected in Table 10. In accordance to Fukui function results,
13
14 for 2HPhAZ the NBO charges results show that higher negative charges are located on the N1
15
and O1 atoms and higher positive charge is acquired by H1. Three carbon atoms (C2, C8a and
16
17 C2') have positive charge due to the presence of highly electronegative nitrogen and oxygen
18
19 atoms. The enol form has the highest negative charges on the O and N atoms as well as the
20
21 highest electronegativity (see Table 7). Thus, enol form has the highest potential to act as a
22 bidentate ligand. In case of 2MPhAZ, the calculated NBO charges indicate that higher negative
23
24 charges are located on the N1 atom and higher positive charge is acquired by H8. Three carbon
25
26 atoms (C2, C8a and C2') have also positive charge due to the presence of highly electronegative
27
28
nitrogen. The thione form has the highest negative charges on the S and N atoms as well as the
29 highest electronegativity (see Table 7). So, the thione form has the highest potential to act as a
30
31 bidentate ligand.
32
33 The charged regions in the molecule can be depicted by ESP maps. The different colors
34
represent different values of the electrostatic potential. The potential increases in the order red <
35
36 orange < yellow < green < blue. The red color in ESP maps represents the most negative
37
38 electrostatic potential while the blue color reflects the most positive electrostatic potential
39
40 regions. The ESP surfaces of investigated structures obtained using B3LYP/6-31G(d,p) are
41 depicted in Figure 4. ESP of enol and keto forms show the localization of a significant negative
42
43 charge on the O atom while the blue color appears around the H7, H8 atoms of azaazulene ring.
44
45 Therefore, the O atom has the highest electron donation ability toward metal ions. A remarkable
46
blue color on the H1 attached to O atoms in rotamer has been observed, and the red color exists
47
48 in the region between the N1 and O1 atoms is due to the decline of H-bonds. For the thiol and
49
50 thione forms the ESP represents that the most negative electrostatic potential on the S atom while
51
52 the most positive electrostatic potential regions appears around the H7, H8 atoms of azaazulene
53 ring.
54
55
56
57
58
59
1
2
3 Table 10. NBO charges of all atomsa of the investigated systems calculated at the B3LYP/6-
4
5
31G(d,p) level of theory in the gas phase.
6 Atom Enol Keto Enol-Rotamer Atom Thiol Thione Thiol-Rotamer
7
N1 -0.557 -0.543 -0.466 N1 -0.528 -0.532 -0.496
8
9 C2 0.229 0.250 0.213 C2 0.230 0.254 0.216
10
11 C3 -0.292 -0.285 -0.300 C3 -0.290 -0.278 -0.293
12
13 C3a -0.066 -0.061 -0.075 C3a -0.070 -0.064 -0.072
14 C4 -0.173 -0.186 -0.170 C4 -0.167 -0.177 -0.168
15
16 C5 -0.239 -0.225 -0.248 C5 -0.241 -0.226 -0.246
17
18 C6 -0.210 -0.228 -0.206 C6 -0.205 -0.219 -0.204
19
C7 -0.233 -0.212 -0.245 C7 -0.236 -0.212 -0.241
20
21 C8 -0.194 -0.236 -0.182 C8 -0.187 -0.226 -0.182
22
23 C8a 0.212 0.229 0.188 C8a 0.208 0.226 0.197
24
25 C1' -0.169 -0.202 -0.125 C1' -0.113 -0.142 -0.099
26
C2' 0.386 0.439 0.368 C2' -0.139 -0.150 -0.137
27
28 C3' -0.293 -0.303 -0.319 C3' -0.248 -0.240 -0.254
29
30 C4' -0.207 -0.206 -0.214 C4' -0.212 -0.209 -0.216
31
32 C5' -0.277 -0.287 -0.270 C5' -0.257 -0.266 -0.253
33 C6' -0.188 -0.192 -0.195 C6' -0.189 -0.191 -0.190
34
35 O1 -0.701 -0.688 -0.667 S1 0.003 -0.252 0.101
36
37 H1 0.522 0.486 0.489 H1 0.194 0.429 0.103
38
H3 0.244 0.252 0.241 H3 0.241 0.252 0.239
39
40 H4 0.246 0.248 0.243 H4 0.246 0.250 0.244
41
42 H5 0.246 0.248 0.243 H5 0.246 0.250 0.244
43
44 H6 0.245 0.247 0.241 H6 0.245 0.249 0.243
45 H7 0.248 0.250 0.244 H7 0.248 0.253 0.246
46
47 H8 0.257 0.258 0.258 H8 0.257 0.261 0.260
48
49 H3' 0.250 0.245 0.231 H3' 0.247 0.253 0.238
50
H4' 0.240 0.237 0.241 H4' 0.242 0.240 0.242
51
52 H5' 0.240 0.237 0.241 H5' 0.241 0.239 0.242
53
54 H6' 0.233 0.229 0.241 H6' 0.233 0.228 0.236
55
56
57
58
59
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15 Enol-form Keto-form Rotamer-form
16
17
18
19
20
21
22
23
24
25
Thiol-form Thione-form Thiol-Rot.-form
26
27
28
29
30
31
32
33
34
35
TST TSR
36
37
38
39
40
41
42
43
44
45
TST(SH) TSR(SH)
46
47
48
49
Figure 4. Molecular ESP surfaces of the investigated structures at B3LYP/6-31G(d,p).
50
51
52
53
54
55
56
57
58
59
1
2
3 3.7. Acidity and basicity
4
5 Our investigated compound has two labile protons which are attached to either nitrogen
6
7 or oxygen/sulfur atom. The reliably and quickly estimation of the acidity and basicity of a
8
9
molecule without synthesis and experimental determination is very important to interpret the
10 structure reactivity and property relationships. Moreover, knowledge of the acidity constants,
11
12 (pKa) is important for determining equilibrium constant (K) of reactions, especially that
13
14 involving proton transfers. However, when determination of pKa experimentally is difficult,
15
computational approaches can be applied to estimate the pKa using thermodynamic free energies
16
17 cycle that is shown in Scheme 2. Consequently, DFT calculations were applied to study the
18
19 protonated (cation) and deprotonated (anion) forms of the 2HPhAZ and 2MPhAZ that are
20
21 depicted in Figure 5. The protonated form, denoted 𝐴𝐻2+ , typically has a net charge of +1, while
22
the corresponding enol/rotamer or keto, AH, is typically neutral. According to the optimized
23
24 structure of deprotonated form, the hydroxyl/mercapto group of phenyl ring has been rotated to
25
26 give the rotamer structure. Therefore, throughout the acidity constant calculation from the
27
28 protonated form we will consider the energy of the rotamer. The deprotonated form, denoted 𝐴 ― ,
29 typically has a net charge of -1. The equations used for calculating pKa values are given below:
30
31
32
33 𝑝𝐾𝑎 = ∆𝐺𝐴𝐻2+ (𝑎𝑞)⁄2.303𝑅𝑇 (1)
34
35 ∆𝐺𝐴𝐻2+ (𝑎𝑞) = ∆𝐺𝐴𝐻2+ (𝑔) +∆∆𝐺𝐴𝐻2+ (𝑠𝑜𝑙𝑣) (2)
36
37 ∆𝐺𝐴𝐻2+ (𝑔) = 𝐺𝐴𝐻(𝑔) + 𝐺𝐻 + (𝑔) ― 𝐺𝐴𝐻2+ (𝑔) (3)
38
39 ∆∆𝐺𝐴𝐻2+ (𝑠𝑜𝑙𝑣) = ∆𝐺𝐴𝐻(𝑠𝑜𝑙𝑣) + ∆𝐺𝐻 + (𝑠𝑜𝑙𝑣) ― ∆𝐺𝐴𝐻2+ (𝑠𝑜𝑙𝑣) (4)
40
41 where Gi(g) is the standard free energy of the species “i” in the gas phase, ΔGi(solv) is the
42 solvation free energy of “i” and Gi(aq) is the free energy change in aqueous phase. The GH + (g)
43
44 and ∆GH + (solv) terms are –6.28 kcal/mol87,88 and –265.90 kcal/mol,89,90 respectively.
45
46 The experimental acidity constants were taken in our consideration. The correlation
47
48 between the experimental and the calculated acidity constants revealed that the B3LYP/6-
49
311++G(2d,2p) level yields the closest pKa value to the experimental values. As given in Table
50
51 11.
52
53
54
55
56
57
58
59
1
2
3  GAH2+(g)
4 AH2+(g) AH (g) + H+ (g)
5
6
7
8
 GAH (solv) GH+(solv)
 GAH2+ (solv)
9
10
11 GAH2+(aq)
12
+
AH2 (aq) AH (aq) + H+ (aq)
13
14 Scheme 2. Thermodynamic cycle connecting gas (g) and aqueous (s) phase for pKa calculation.
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40 Protonated ( 𝑨𝑯𝟐+ ) Deprotonated (A-)
41
42
Figure 5. The optimized structure of protonated (𝐴𝐻2+ ,cation) and deprotonated (A-, anion)
43
forms of 2HPhAZ and 2MPhAZ at B3LYP/6-31G(d,p).
44
45
46
47 The experimental pKa of 2HPhAZ was reported as 12.726 and the calculated pKa from
48
49 the protonation form is found as 15.84, 11.25 and 8.23 using B3LYP/6-31G(d,p), B3LYP/6-
50 311++G(2d,2p) and M06-2X/6-311++G(2d,2p) levels, respectively. By comparing the pKa
51
52 obtained by deprotonation, we can found that the enol form is a weaker acid than its keto and
53
54 rotamer forms. This can be attributed to the strength of the OH and NH bonds, presence or
55
absence of hydrogen bonds, and the stability of the resulting conjugate base upon deprotonation.
56
57
58
59
1
2
3 For 2MPhAZ, the calculated pKa obtained by deprotonation presents that the thione form is a
4
5 weaker acid than the thiol and its rotamer forms. That matches with the weaker of SH bond than
6
7 OH and NH bonds. More negative charges on the nitrogen and oxygen atoms for enol than keto
8
9
and enol-rotamer forms (Table 8 and 10) might reflect the strength of the OH and NH bonds.
10 In this study, we examine the intrinsic basicity in the gas phase that can be given by
11
12 proton affinity (PA) which is the negative of the protonation reaction of AH.
13
14 AH + H+→ AH2+ , PA= -ΔHº
15
16
According to The previous study on 2-Pyridone tautomers and rotamer,[67] Michelson et
17 al. found that the stable enol form has lower PA followed by keto form with difference 5.7
18
19 kcal/mol at M06-2X/6-311+G(2df,2p) and the rotamer has slightly higher PA. Our calculated
20
21 PA of 2HPhAZ tautomer differs by 6.9 kcal/mol (239.12 (enol) versus 246.00 kcal/mol (keto)),
22
while the rotamer form is slightly higher in the calculated proton affinity, 252.67 kcal/mol at
23
24 B3LYP/6-311++G(2d,2p) level. For 2MPhAZ, the calculated PA has a slight differences
25
26 between tautomer and its rotamer (255.46 (thiol) versus 256.53 (thione) and 257.46 kcal/mol for
27
28 thiol-rotamer at B3LYP/6-311++G(2d,2p) level). That proves the stability of mercapto analogue
29 and the expectation of the presence a mixture of tautomer and rotamer of 2MPhAZ. The
30
31 calculated PA at B3LYP/6-31G(d,p), B3LYP/6-311++G(2d,2p) and M06-2X/6-311++G(2d,2p)
32
33 levels has been listed at Table 2S. The higher energy of keto and rotamer forms gives evidence
34
35
about the stabilization and predominnce of enol form of 2HPhAZ in nature.
36
37
38 Table 11. The calculate acidity constant (pKa ) for the protonated and deprotonated forms in
39
40 ethanol at B3LYP and M06-2X a
41
B3LYP/6-31G(d,p) B3LYP a M06-2X a
42
43 𝑨𝑯𝟐+ → AH + H+ 15.54 11.25 8.23
44 AH (enol) → A- + H+ 28.90 21.30 20.44
45 AH (keto) → A- + H+ 26.55 19.92 16.84
46
47 AH (rotamer) → A- + H+ 21.97 15.50 15.51
48 +
𝑨𝑯𝟐(𝑺𝑯) → AH(SH) + H+ 5.02 1.23 -2.88
49 - +
50
AH (thiol) → A + H 21.20 15.94 12.67
51 AH (thione) → A- + H+ 22.07 20.05 16.42
-
AH (thiol-rotamer) → A + H + 19.05 14.63 12.34
52
53 a Method /6-311++G(2d,2p)// B3LYP/6-31G(d,p)
54
55
56
57
58
59
1
2
3 3.8. UV-Vis spectral analysis
4
5 Potential use of any compound as a dye or sensor can be deduced from its photophysics
6
7 and photochemistry. The first maximum wavelength using TDDFT calculation of the 2HPhAZ in
8
9
the gas phase by means of different solvation models PCM, CPCM and SMD at different level of
10 theory such as B3LYP, CAM-B3LYP, PBE,PBE0, ωb97X-D, M06-2X and CIS with the 6-
11
12 311+G(d,p) basis sets is collected in Table 12. The results of calculations are compared with the
13
14 available experimental data. The TDDFT-PBE/SMD model chemistry exhibits a good
15
quantitative agreement regarding the first and second maximum excitation peak (Eex; the
16
17 discrepancy between the calculated and experimental first maximum and second excitation
18
19 energy 0.06/0.07 and 0.09 eV, respectively).65
20
21
22 Table 12. First λmax for 2HPhAZ using different functionals(model, acetonitrile)/6-
23
311+G(d,p)//B3LYP/6-31G(d,p) with a variety of solvation models (experimental value is 495
24
25 nm)
26
27 Model B3LYP CAM-B3YP PBE PBEa ωB97X- M06-2X CIS
28 \functional D
29
CPCM 448 423 513 514 422 422 361
30
31 (0.2715) (0.2067) (0.2005) (0.2005) (0.1906) (0.2048) (0.5763)
32 SMD 445 420 506 508 418 419 360
33 (0.2765) (0.2166) (0.2131) (0.2125)b (0.2003) (0.2143) (0.6115)
34 PCM 447 422 512 513 421 421 358
35 (0.2626) (0.1992) (0.1934) (0.1933) (0.1836) (0.1973) (0.5405)
36 Gas phase 459 429 553 552 429 428 386
37
(0.2169) (0.1523) (0.1051) (0.1054) (0.137) (0.1513) (0.2389)
38 aPBE/6-311+G(2d,2p)
39
b The result of PBE0/6-311+G(2d,2p) using SMD model is 436 nm (0.2739)
40
41
42
43 The hydrogen bond is one of reasons responsible for the strength, broading and shift of
44
the absorption peaks. Table 13 presents the values of Eex and f and transition configurations of
45
46 the intense peaks for enol, keto and rotamer and their mercapto analogue. The keto form with the
47
48 strongest HB is accompanied by a large red-shift (until 800 nm) followed by the enol form (until
49
50 650 nm), and the lower shift has been found with the rotamer (until 550 nm) as depicted in
51 Figure 6. For 2MPhAZ, the thione form is accompanied by the largest red-shift (until 1000 nm)
52
53 followed by the thiol form (until 700 nm) and its rotamer (until 650 nm) as shown in Figure 6.
54
55 As expected from the lower Eg value of the keto, enol and rotamer and their mercapto analogue
56
57
58
59
1
2
3 (Table 7), the maxima in the electronic absorption spectra of thion/keto in comparison with
4
5 thiol/enol and their rotamer are shifted bathochromically by 16/17 and 20/66 nm, respectively.
6
7 The intense peaks in the UV-Vis spectra of thione/keto spread over the range of 348-783/346-
8
9
638 nm followed by thiol/enol that illustrates spreading over the range 332-561 /272-506 nm,
10 and the their rotamer peaks spread over the range 294-531/280-479 nm. The strong electronic
11
12 absorption of thione/keto is attributed to the HOMO-3 to LUMO and HOMO-2 to LUMO+1
13
14 transitions. The maximum absorption peak fort thiol/enol appears at lower wavelength than
15
thione/keto is attributed to HOMO-2 to LUMO+1 and HOMO-1to LUMO+1 transitions. The
16
17 strong electronic absorption of rotamer is mainly due to the HOMO-1 to LUNMO+2 transitions.
18
19 The strong electronic absorption of thiol-rotamer is mainly due to the HOMO-2, HOMO-1 and
20
21 HOMO to LUNMO+1 transition. The strong electronic absorption of rotamer is mainly due to
22 the HOMO-1 to LUNMO+2 transitions. It might be worth noting that our investigated compound
23
24 particularly the 2MPhAZ tautomer and its rotamer have absorption in visible region, which will
25
26 be suitable for many applications such as sensing and a dye in solar cells.
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1
2
3 Table 13. Excitation energies (eV) at (TD-PBE-SMD,acetonitrile)/6-311+G(d,p)//B3LYP/6-
4
31G(d,p), oscillator strengths (f > 0.1), and their transition characters for the studied compound.
5
6
7 Compound State Ea f Assignmentb
8
9 1 2.45 (506) 0.2131 H→L (88%)
10
4 3.28 (378) 0.2137 H-2→L (55%), H-1→L+1 (27%), H→L+1 (11%)
11
12 6 3.76 (329) 0.2990 H-2→L (10%), H-2→L+1 (27%), H-1→L+1 (40%), H→L+1
13 (12%)
14 Enol
7 4.07 (305) 0.1317 H-4→L (20%), H→L+2 (73%)
15
16 8 4.18 (297) 0.2947 H-4→L (27%), H-2→L+1 (45%), H-1→L+1 (13%), H→L+2
17 (10%)
18 10 4.56 (272) 0.1311 H-2→L+2 (14%), H-1→L+2 (73%)
19
20 1 2.21(561) 0.1041 H→L (91%)
21
22 Thiol 5 3.22(385) 0.1554 H-3→ L (35%), H-2→ L (42%), H-1→ L+1 (17%)
23
24 6 3.73(332) 0.3052 H-2→ L (11%), H-2→L+1 (17%), H-1→L+1 (50%)
25
26 1 1.94 (638) 0.2023 H→L (89%)
27
28 Keto 4 2.81 (441) 0.1868 H-2→L (90%)
29
30 7 3.59 (346) 0.4396 H-3→L (40%), H-2→L+1 (34%), H→L+2 (14%)
31
32 1 1.58 (783) 0.1103 H→L (94%)
33
34 Thione 5 2.72(456) 0.2522 H-2→ L (91%)
35
36 9 3.57 (348) 0.2752 H-3→ L (38%), H-2→L+1 (38%)
37
38 1 2.59 (479) 0.1951 H→ L (88%)
39
40 5 3.36 (369) 0.1304 H-2→L (26%), H-1→L+1 (32%), H→L+1 (25%)
41
42 6 3.84 (323) 0.2506 H-4→L (15%), H-2→L+1 (31%), H-1→L+1 (26%), H→L+1
Rotamer
43 (17%)
44 9 4.17 (297) 0.2348 H-3→L+1 (13%), H-2→L+1 (16%), H→L+2 (50%)
45
10 4.43 (280) 0.3647 H-1→L+2 (70%)
46
47 1
48 2.33 (531) 0.1186 H→ L (89%)
49 5
50 3.25 (382) 0.2400 H-2→ L (54%), H-1→ L+1 (27%), H→L+1 (10%)
Thiol-Rot.
51 6 3.78 (328) 0.2639 H-2→ L+1 (24%), H-1→ L+1 (39%), H→ L+1 (12%)
52
53 10 4.21 (294) 0.1658 H-4→ L (10%), H-1→ L+3 (17%), H→ L+3 (55%)
54
55 aValues
56 in parentheses are given in nm.
57
58
59
1
2
3 bOnly contributions above 10% are shown. H and L represent HOMO and LUMO, respectively.
4
5
6
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35 Figure 6. The simulated UV/Vis absorption spectra for the keto, enol and rotamer of 2HPhAZ
36 and 2MPhAZ at TD-PBE/6-311+G(d,p)
37
38
39
40 2. CONCLUSIONS
41
Tatuomers and the related rotamer of 2-(2-Hydroxyphenyl)-1-azaazulene (2HPhAZ) and
42
43 their mercapto analogue (2MPhAZ) were theoretically investigated using the DFT (B3LYP)/6-
44
45 31G(d,p), B3LYP/6-311++G(2d,2p) and M06-2X/6-311++G(2d,2p) methods for analysis
46
47 various molecular properties, stability and aromaticity. B3LYP/6-311++G(2d,2p) was compared
48 with B3LYP/6-31G(d,p) where a small difference in the relative energies for the system under
49
50 consideration. The structural parameters and vibrational frequencies have been discussed at
51
52 B3LYP/6-31G(d,p) and compared with the available experimental data. Comparisons with
53
54
experiment of 2-(2-Hydroxyphenyl)-1-azaazulene show a very good agreement. Both B3LYP
55 and M06-2X methods demonstrate thermodynamic and kinetic stability of the enol form in a
56
57
58
59
1
2
3 good agreement with the presence of enol experimentally exclusively as the most stable tautomer.
4
5 While the thiol form is thermodynamically and kinetically stable in gas phase, the thione form is
6
7 highly stable in ethanol solvent. The sites of electrophilic and nucleophilic were determined
8
9
using Fukui functions. UV absorption spectra (in the gas phase and ethanol) were examined by
10 TD-DFT using B3LYP, CAM-B3LYP, PBE, PBE0, ωb97X-D, M06-2X and CIS methods with
11
12 the 6-311+G(d,p) basis sets for the title compounds. The TDDFT-PBE/SMD approaches exhibit
13
14 good quantitative agreement regarding the first and second maximum excitation peaks.
15
16
17 Author’s Contribution Asmaa B. El-Meligy: Conceptualization, Methodology, Formal analysis,
18
Data curation, Validation, Visualization, Investigation, Writing-review & editing, Safinaz H. El-
19
20 Demerdash: Conceptualization, Methodology, Formal analysis, Data curation, Validation,
21 Visualization, Investigation, Writing- review & editing. Mohamed A. Abdel-Rahman
22
Conceptualization, Methodology, Formal analysis, Data curation, Validation, Visualization,
23
24 Investigation, Writing-review & editing, Mohamed A. M. Mahmoudc Conceptualization,
25 Methodology, Formal analysis, Data curation, Validation, Visualization, Investigation, Writing-
26
review & editing.Ahmed M. El-Nahas: Formal analysis, Data curation, Validation, Visualization,
27
28 Investigation, supervision, Writing—review & editing. All authors read and approved the final
29 manuscript.
30 Funding This research has no funding.
31
32 Availability of data and material (data transparency) Electronic supporting information data
33 file is submitted. All data and materials support the published claims and comply with field
34 standards.
35
36 Code availability N/A.
37 Declarations
38 Ethics approval Authors certify that they follow the journal ethics to the best of their knowledge.
39
40 Consent to participate Authors certify the Consent.
41 Consent for publication Authors certify the Consent.
42 Conflict of interest The authors declare no conflict of interest
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Structures, Energetics, and Spectra of (NH) and (OH)

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