Spectroscopic study of 2-, 4- and 5-substituents on pKa values of imidazole heterocycles prone to intramolecular proton-electrons transfer

Article abstract of DOI:10.1016/j.saa.2009.11.041

New 2-(1H-imidazol-2-yl)phenols (L1Et-L8tBuPt) bearing a phenolic proton in the vicinity of the imidazole base were prepared and characterized. Experimental studies of the dependence of their protonation/deprotonation equilibrium on substituent identities

Full text of DOI:10.1016/j.saa.2009.11.041

Spectrochimica Acta Part A 75 (2010) 693–701
Contents lists available at ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Spectroscopic study of 2-, 4- and 5-substituents on pKa values of imidazole
heterocycles prone to intramolecular proton-electrons transfer
Abiodun O. Eseolaa,b,∗, Nelson O. Obi-Egbedic
a Chemical Sciences Department, Redeemer’s University, Redemption City, Km. 46 Lagos – Ibadan Expressway, Nigeria
b Beijing National Laboratory for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China
c Chemistry Department, University of Ibadan, Ibadan, Nigeria
a r t i c l e i n f o
a b s t r a c t
Article history:
New 2-(1H-imidazol-2-yl)phenols (L1Et–L8tBuPt) bearing a phenolic proton in the vicinity of the
imidazole base were prepared and characterized. Experimental studies of the dependence of their
protonation/deprotonation equilibrium on substituent identities and intramolecular hydrogen bond-
ing tendencies were carried out using electronic absorption spectroscopy at varying pH values. In
order to make comparison, 2-(anthracen-10-yl)-4,5-diphenyl-1H-imidazole (L9Anthr) bearing no phe-
nolic proton and 4,5-diphenyl-2-(4,5-diphenyl-1H-imidazol-2-yl)-1H-imidazole (L10BisIm) bearing two
symmetrical imidazole base fragments were also prepared and experimentally investigated. DFT calcu-
lations were carried out to study frontier orbitals of the investigated molecules. While electron-releasing
substituents produced increase in protonation–deprotonation pKas for the hydroxyl group, values for
the imidazole base were mainly affected by polarization of the imidazole ring aromaticity across
the 2-imidazole carbon and the 4,5-imidazole carbons axis of the imidazole ring. It was concluded
that electron-releasing substituents on the phenol ring and/or electron-withdrawing substituents on
4,5-imidazole carbons negatively affects donor strengths/coordination chemistries of 2-(1H-imidazol-2-
yl)phenols, and vice versa. Change of substituents on the phenol ring significantly altered the donor
strength of the imidazole base. The understanding of pKa variation on account of electronic effects
of substituents in this work should aid the understanding of biochemical properties and substituent
environments of imidazole-containing biomacromolecules.
Received 19 September 2009
Received in revised form
12 November 2009
Accepted 17 November 2009
Keywords:
Ionization constants
UV spectroscopy
pKas
Protonation–deprotonation
Substituent effects
© 2009 Elsevier B.V. All rights reserved.
1. Introduction
of supramolecular folding that exists in biological macromolecules,
investigation of behaviours of pH sensitive functions is hindered.
For the past many decades, interest in the understanding of
factors controlling the mechanisms of reactions of biological and
medicinal interests has been sustained [1–5]. Coupled proton-
electron transfer is a subject of significant current interest [6–9]
and physicochemical data such as ionization constant values
(often derived as pKas) are routinely employed in characterizing
biomolecules such as metalloenzymes, amino acids, etc. The pKa
of a drug is one of the most important parameters employed to
explain its physicochemical behaviour and acid-base properties,
and to study pharmaceutical pre-formulations [10]. Changes in pKa
values in biological macromolecules are often investigated to estab-
lish modes of interactions between an acid or base fragment and
its neighbouring functional groups [11]. However, in the presence
Small, well-characterized, organic molecules provide access to
understanding of phenomena observed in the macrostructures.
Spectroscopic determination of ionization constant of weak acids
or bases is of widespread application and considered suitable even
at extremes of pH, poor solute solubilities and for species prone
to conformational photo-tautomerism [11–13]. Aqueous–organic
mixtures are often employed for various pH buffers in ionization
constant determinations [10].
Moieties such as adenine, guanine, histidine, etc., contain
imidazole functions and are involved in intramolecular and inter-
molecular chemistries of biological macromolecules under pH
specific conditions [14–18]. Imidazole base of histidine is recog-
nized to be an interesting ligand in the bioinorganic chemistry of
most heamoptoteins of which investigation of basicity and steric
effects gives understanding of the role of the leaving group in con-
trolling mechanisms [9,19]. In previous studies on histidine, it is
believed that pKa values assigned to the imidazole ring (pKa ≈ 6) is
distinguishable from values ascribed to carboxy (pKa ≈ 2) or amino
(pKa ≈ 9) functionalities [1,2,11]. However, pKa values of some
∗
Corresponding author at: P.M.B. 3005, Redemption City, Ogun State – Nigeria.
Tel.: +234 7062192104.
E-mail addresses: bioduneseola@run.edu.ng, bioduneseola@hotmail.com
(A.O. Eseola).
1386-1425/$ – see front matter © 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.saa.2009.11.041

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Scheme 1. Molecular frameworks investigated in this work.
imidazole bases have been reported to be inaccessible within the
pH scale range [20]. On account of protonation–deprotonation reac-
tions, spectroscopic behaviour of imidazole base chromophores
have attracted considerable attention towards potential pH sensory
and fluorescence switching applications [21–29]. Proper under-
standing of donor–acceptor properties of imidazole bases in the
presence of different neighbouring functionalities is still lacking.
As discussed in our previous report on 1H NMR comparison [30],
protonation and deprotonation schemes have been concluded for
an oxazole system which the authors wrongly thought to be an
imidazole ligand [29]. Progress has been made in the understand-
ing Excited State Intramolecular Proton-electron Transfer (ESIPT)
phenomenon of 2-(imidazol-2-yl)phenols [31–35]. However, such
studies have been largely restricted to 2-(1H-benzo[d]imidazol-
2-yl)phenols with scarce knowledge of substituent and solute
media effects. In preceding experiments recently published on a
series of ligands and their corresponding zinc complexes involving
some of the compound in the present studies, the role of sub-
stituents and solvents media in preventing ESIPT was presented
and changing solvent polarities from tetrahydrofuran (THF, dielec-
tric constant ≈7) to dimethylformamide (DMF, dielectric constant
≈38) yielded little or no change on absorption peak positions (i.e.
0–2 nm shifts). However, observed shifts in photoluminescence
maxima (spread over 1–57 nm) for the reported imidazole-phenol
ligands as a result solvent variation (from THF to DMF) indicated
that significant change in polarities for polar solvents produced
significant modification of excited state electronic characteristics
while having insignificant effects on the ground state elec-
tronic structures [36]. Calculational reports also largely restricted
to 2-(1H-benzo[d]imidazol-2-yl)phenols are known [37,38]. The
B3LYP/6–311 + G* basis set has been successfully employed as
a reliable method in DFT calculations of imidazole organic sys-
tems [39]. Investigation of the consequence of intramolecular
proton–base interactions on physicochemical parameter such as
ionization constants of the proton donor as well as the acceptor is
unknown.
Owing to importance of imidazole bases, attention has been
drawn to investigation of small molecules containing imidazole
nucleus, and such studies are yet few. Moreover, works involving a
series of imidazole bases with differing substituent environment
is also scarce. Particularly, studies of substituent environments
on ionization constants of imidazoles prone to intramolecular
proton–electron transfer have not been reported. Herein, we
present our results on syntheses and spectroscopic investigation of
ionization constants for a series of 2-aryl-1H-imidazoles. Two imi-
dazole molecules that lack intramolecular proton–electron transfer
capacities have been included for comparison. Calculated proper-
ties based on optimized geometries of the molecules as well as
experimental 1H NMR and FTIR data of active protons were dis-
cussed in attempt to rationalize observed variations in ionization
constants (Scheme 1).
2. Experimental
2.1. General considerations
All manipulations of oxidation-prone reactions were performed
under nitrogen atmosphere using standard Schlenk techniques.
All starting materials were obtained commercially as reagent
grades and used without further purification. L1Et, L2Ph, L3m-
Scheme 2. Possible protonation states for base and active proton components. (a), (b) and (c) were observed within pH 0–14.

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695
Fig. 1. Overlays of absorption spectra at different pH values for (a) L1Et, (b) L7tBuPh and (c and d) L6Me.
OMe, L4p-OMe, L6Me, L7tBuPh and L8tBuPt were prepared
according to recently published procedures [36]. The synthe-
sized organic compounds were purified on silica gel column to
exclude impurities. Elemental analyses were performed on a Flash
EA 1112 microanalyzer. 1H and 13C NMR spectra were recorded
on a Bruker ARX-400 MHz instrument using deuterated chloro-
form as solvent and TMS as internal standard. IR spectra were
recorded on a Nicolet 6700 FT-IR spectrometer as KBr discs in the
range of 4000–600 cm−1. UV–vis measurements were recorded on
Shimadzu 1600 Spectrophotometer. The pKa determination exper-
iments were done using ≈10−5 M solutions of the compounds in
ethanol–water mixture which consists of 70% absolute ethanol
and 30% distilled water. Calculated amount of potassium chlo-
ride was used to achieve 0.1 M concentration of the salt in order
to maintain fairly constant ionic strength and the pH of solutions
were adjusted with the aid of a calibrated pH meter and through
addition of potassium hydroxide or hydrochloric acid solutions.
Optimized geometries and calculated properties were obtained
through DFT calculations conducted at the B3LYP/6–311 + G* level
with input files created based on simulated dielectric constants for
70% ethanol–water mixture. DFT calculations were obtained using
Gaussian 98 package of programs [41].
2.2. Preparation of imidazoles
1-(4,5-Diphenyl-1H-imidazol-2-yl)naphthalen-2-ol
(L5Naph):
Benzil (2.00 g, 9.51 mmol), 2-hydroxynaphthalene-1-carbaldehyde
(1.64 g, 9.51 mmol) and ammonium acetate (14.67 g) refluxed for
2 h in 10 mL glacial acetic acid. The reaction mixture was allowed
to cool, transferred to 40 mL water, carefully neutralized with
concentrated aqueous ammonia and the crude product filtered.
After washing with water, the dried solid was recrystallized from
ethanol to yield the L5Naph as yellow micro-needles (2.23 g,
64.7%). Selected IR peaks (KBr disc, cm−1): ꢀ 3245vs, 3052m,

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A.O. Eseola, N.O. Obi-Egbedi / Spectrochimica Acta Part A 75 (2010) 693–701
Fig. 2. (a) Energy separation between LUMO, HOMO and HOMO-1 energy levels in
the studies molecules and (b) atoms labeling scheme for Mulliken charges reported
in Table 2.
1667w, 1619s, 1598s. 1H NMR (400 MHz, TMS, CDCl3); ı 8.21 (d,
J = 8.4 Hz, 1H); 7.86 (d, 8.0 Hz, 1H), 7.79 (d, 8.8 Hz, 1H); 7.62 (d,
7.2 Hz, 4H); 7.57 (dd, 7.2 Hz, 1H); 7.39 (m, 7H). 13C NMR (400 MHz,
CDCl3, TMS); 157.52, 145.73, 130.57, 128.74, 127.79, 123.06,
118.95, 117.85, 112.47. Anal. calc. for C25H18N2O.0.2H2O (M. wt.,
444.12): C, 82.21; H, 5.17; N, 7.57. Found: C, 82.43; H, 5.64; N, 7.13.
2-(Anthracen-9-yl)-4,5-diphenyl-1H-imidazole (L9Anthr): Ben-
zil (0.21 g, 0.98 mmol), 9-anthraldehyde (0.20 g, 0.98 mmol) and
ammonium acetate (1.51 g, 19.60 mmol) were refluxed in glacial
acetic acid (3 mL) for 2 h. The cooled reaction solution was
diluted with cc. 10 mL water, carefully neutralized using con-
centrated aqueous ammonia and the precipitate filtered, washed
with distilled water and the crude precipitate was extracted into
dichloromethane. The organic extract was purified on silica gel
column using petroleum ether:dichloromethane:ethyl acetate in
10:3:1 ratio to obtain L9Anthr as yellow micro-needles (0.37 g,
95%). Selected IR peaks (KBr disc, cm−1): ꢀ 3383s, 3053vs, 1606s,
1529s, 1505s. 1H NMR (400 MHz, TMS, CDCl3); ı 9.29 (s, 1H, imi-
dazole); 8.54 (s, 1H, anthr.), 8.02 (d, J = 9.6 Hz, 4H, anthr.); 7.80 (br,
2H, anthr.); 754 (br, 2H, anthr.); 7.46 (m, 4H, phenyl); 7.34 (br, 6H,
phenyl). Anal. calc. for C25H18N2O.0.2H2O (M. wt., 444.12): C, 82.21;
H, 5.17; N, 7.57. Found: C, 82.43; H, 5.64; N, 7.13.
4,5-Diphenyl-2-(4,5-diphenyl-1H-imidazol-2-yl)-1H-imidazole
(L10BisIm): Benzil (5.00 g, 23.80 mmol), ammonium acetate
(25.00 g, 356.74 mmol) and glacial acetic acid (20 mL) were heated
under reflux condition and, while under reflux, glyoxal water
(2.7 mL, 23.78 mmol) was added over 20 min. Reflux was allowed
to continue for 2 h 30 min. followed by cooling, dilution in ≈50 mL
water and neutralization with concentrated aqueous ammonia
solution. The aqueous solution was decanted from the brown,
gummy residue was extracted using dichloromethane and purified
on silica gel column using petroleum ether/ethyl acetate in ration
10:1. Pure product was obtained as white micro-crystals (<5%
yield). Selected IR peaks (KBr disc, cm−1): ꢀ 3440s, 3050m, 1620w,
1578w, 1389vs, 765vs. 1H NMR (400 MHz, TMS, CDCl3); ı 7.46 (m,
8H); 7.33 (m, 12H). Anal. calc. for C30H22N4·(1/2)H2O: C, 80.51; H,
5.18; N, 12.52. Found: C, 80.55; H, 5.37; N, 12.35.
3. Results and discussion
3.1. Absorption properties at different protonation states
Table 1 contains the experimental spectral and pKa data for the
investigated molecules. For reliable determination of pKa values,

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697
Table 2
Ligand dipole moments, LUMO–HOMO separations and Mulliken charge densities of selected atoms determined at the B3LYP/6–311 + G* level.
Ligands
DM (D)a
ꢂE(LUMO)–(HOMO) (eV)b
Mulliken charge densities (Q)
N(1)
N(2)
N(1)–N(2)
O(1)
C(1)
L1Et
L2Ph
5.865
5.869
3.292
4.784
5.283
5.511
6.020
5.183
2.627
0.347
8.420
7.927
7.907
7.993
5.894
7.928
6.881
6.784
3.399
7.951
−0.616
−0.613
−0.621
−0.603
−0.642
−0.616
−0.623
−0.630
−0.542
−0.459
−0.478
−0.491
−0.498
−0.488
−0.489
−0.492
−0.491
−0.537
−0.495
−0.412
0.138
0.122
0.123
0.115
0.164
0.124
0.132
0.089
0.048
0.047
−0.223
−0.214
−0.209
−0.222
−0.204
−0.223
−0.245
−0.234
NAc
0.458
0.462
0.471
0.452
0.488
0.442
0.439
0.434
0.473
0.451
L3m-OMe
L4p-OMe
L5Naph
L6Me
L7tBuPh
L8tBuPt
L9Anthr
L10BisIm
NAc
a
Dipole moments in Debye.
b
LUMO = lowest unoccupied molecular orbital; HOMO = highest occupied molecular orbital. eV = electron Volts. Selected atomic labels correspond to notations according
to Fig. 4(b).
c
NA = not applicable.
it is desirable to have absorption bands that are significantly dis-
tinguishable at the different protonation states. Fortunately, the
protonation–deprotonation reactions in this work afforded species
with different absorption band positions and/or shapes (Scheme 2,
Fig. 1). Three protonation states were observed within pH 1–14,
which corresponds to imidazolium cation (lower pH end), neu-
tral imidazole-phenol (pH ≈5–9) and imidazole-phenolate anion
(higher pH end). Use of spectral absorption methods in quanti-
fying concentrations of equilibrium species in solution has been
known to render reliable results [40]. The ionization constants were
obtained as pKa on the basis of Henderson–Hasselbalch theory:
where A0 and Af represent the initial and final absorbance val-
ues for the various protonated–deprotonated species, respectively.
Though solutions of similar concentrations were planned, wide
variation in extinction coefficients were observed due to sub-
stituent variations. Similar trend was also observed in substituent
effects on THF solution for some of the ligands studied [36].
The pKa values were obtained from sigmoidal fittings on plots of
absorbance values at wavelengths of maximum difference between
the absorbance of protonated and deprotonated forms against pH
(inset, Fig. 1(c)). R2 values were in the range 0.9744–0.9997.
It is noteworthy that the longest wavelength absorption
bands of the imidazole-phenol ligands progressively exhibited
red shift on transforming from the imidazolium forms into the
A − A0
pH = pKa − log
Af − A
Fig. 3. Optimized structures of L1Et (a–c), L8tBuPt (d–f) and L10BisIm (g–i) showing the frontier molecular orbitals at LUMO, HOMO and HOMO-1 levels. Hydrogen atoms
were omitted for clarity.

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Fig. 4. Optimized structures of L2Ph (a–c), L6Me (d–f) and L7tBuPh (g–i) showing the frontier molecular orbitals at LUMO, HOMO and HOMO-1 levels. Hydrogen atoms
were omitted for clarity.
neutral species and into the phenolate forms (Table 1). How-
ever, absorption maxima of the second absorption bands were
less sensitive to the protonation–deprotonation events except
for gradual changes in absorbance or peak position (Fig. 1(a)).
Also notable is the observed sudden jump in molar extinction
coefficient (≈×5) of the shortest wavelength band of the imidazole-
phenols (≈220 nm) at higher alkalinities (pH ≈12–14), which was
accompanied by relatively little or no change in intensity of the
longer wavelength bands (Fig. 1(d)). This observation may be
of value to pH sensory research. The bis-imidazole molecule
L10BisIm showed no change in absorption characteristics over
pH 1–14. This observation is attributable to the symmetrical
nature of the ligand and consequent lack of dipole tendencies.
This view is supported by the broad ꢀN–H frequency due to fast
intramolecular proton transfers between the two imidazole
nitrogen atoms (Fig. 4(d)). The pKa values for L10BisIm probably
exist outside the pH scale range. DFT calculations on the series
of molecules showed good inverse agreement between trends of
S0–S1 absorption peak wavelengths (nm) and the energy sepa-
rations between respective highest occupied molecular orbitals
(HOMO) and lowest unoccupied molecular orbitals (LUMO)
levels (e.g. L1Et: ꢂE(LUMO)–(HOMO) = 8.420 eV, ꢁmax = 311 nm;
L5Naph: ꢂE(LUMO)–(HOMO) = 5.894 eV, ꢁmax = 344 nm; L9Anthr:
ꢂE(LUMO)–(HOMO) = 3.399 eV, ꢁmax = 365 nm; Fig. 2; Table 2).
carbons simultaneously produced lowering of imidazole base pKas
and increase of the phenolic hydroxyl group pKas (Table 1; L1Et:
6.64–11.91; L6Me: 3.38–11.64; L7tBuPh: 2.28–13.47; L8tBuPt:
1.11–13.04). The separation in pKa values produced by a combi-
nation of push–pull substituents, which was achieved through tBu
and 4,5-diphenyl or phenanthreneyl substitution as in the cases
of compounds L7tBuPh and L8tBuPt, is notable. In other words,
as the ␲-electron cloud of the imidazole ring is shifted from the
2-carbon towards the 4,5-carbons, it’s protonation–deprotonation
equilibrium constant becomes larger (i.e. lower pKa values). This
implies that the donor ability of the imidazole base is reduced
and effective protonation of species in solution could only be
achieved in lower pH media (i.e. higher [H+]). Calculated charge
densities revealed a decrease in positive charge density on the 2-
imidazole carbon which suggests a push of negative charge from
the phenol ring towards the imidazole ring in the order L2Ph
(0.462) > L6Me (0.442) > L7tBuPh (0.439) > L8tBuPt (0.432 having
a combination of push and pull) (Table 2). Increase in the calcu-
lated electronic density on the oxo-atom of the phenol group also
indicates expected push of electron density towards 2-imidazole
position in the order L7tBuPh (−0.245) > L6Me (−0.223) > L2Ph
(−0.214). Furthermore, the electron-releasing group on the phenol
ring strengthened the phenolic O–H bond as established by FTIR
data (Table 1) and a weaker strength of intramolecular H-bonding
is thus implied. Increasing pKa values for the deprotonation equi-
librium of phenolic O–H on account of greater electron-releasing
character of phenol ring substituents is in support of the conse-
quent strengthening of O–H bonds. The pKa data in the present
work also provides understanding towards metal–organic chela-
tion reactivity of 2-(1H-imidazol-2-yl)phenols. A combination of
3.2. Substituent effects and trends in pKa values
Increase in electron-releasing capacity of the phenol ring
towards the 2-position of the imidazole ring or increase in electron-
withdrawing character of substituents on the 4,5-imidazole

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699
Fig. 5. (a–d) Solid-state FTIR spectra (as KBr disc) of studied molecules in this work.
push–pull substituents as in L7tBuPh and L8tBuPt leads to poor
imidazole N-donor strength and tougher phenolic O–H deprotona-
tion. As observed in previously published work [36], coordination
of L7tBuPh and L8tBuPt with zinc(II) ion was achieved only
in the presence of triethylamine base. The product yield was
quite low and the complexes decomposed in polar-protic sol-
vents.
[36], it was observed that the C–C bond lengths between the 4- or
5-carbon of the imidazole ring and the substituent ethyl groups
are typical of single bonds (average of 1.507 Å), while the cor-
responding lengths to the phenyl substituted analogue indicated
some extent of resonance conjugation across the C–C bond (average
of 1.475 Å). Fig. 3 presents frontier orbital diagrams for the opti-
mized molecular geometries of L1Et, L8tBuPt and L10BisIm while
Fig. 4 contains those for L2Ph, L6Me and L7tBuPh, respectively.
The HOMO frontier orbitals were mainly found to be concentrated
on the imidazole rings (Figs. 3 and 4) and this may explain why
the phenol substituent perturbations produced greater effects on
pKas of imidazole base than on the phenolic hydroxyl function.
Two alternative forms of orbitals alignments were observed to
exist in the HOMO and HOMO-1 levels and which are energetically
close (0.045–0.945 eV). The electron densities were either aligned
across the N–N–O hetero atom axis (e.g. Fig. 3(b) and (e); Fig. 4
(b), (e), (h)) or along the length of the molecule (Fig. 3(h)). It is
noteworthy that the former case occurred in the HOMO level of all
studied molecules except for the symmetrical L10BisIm where the
later case formed the HOMO level. This observation supports the
importance of intramolecular hydrogen bonding in this family of
molecules unlike for L10BisIm where such bonding was not appli-
cable. This view was also supported by the lower dipole moments
or lowest difference between N-atom charge densities for com-
pounds L9Anthr and L10BisIm (Fig. 2, Table 2). The imidazole
ring substituents in this work contributed to shift the imidazole
aromatic ␲-density towards the 4,5-carbons in the order phenan-
throleneyl > 4,5-diphenyl > 4,5-diethyl. This order is opposite to the
effect of 4,5-substituent on donor strength of imidazole nitrogen
base. Therefore, it is suggested that, from the ionization constant
of imidazole-containing biomacromolecules, nature of unknown
Relative to the pKa data for L2Ph, data for L4p-OMe sug-
gest that the electron-rich methoxy group para- to the hydroxyl
function is electron-releasing towards the imidazole ring in con-
trast to substituent effect of the methoxy group on L3m-OMe.
Mulliken positive charges on the 2-carbon of the imidazole ring,
which decreased for L4m-OMe (0.452) and increased for L3m-
OMe (0.471) relative to L2Ph (0.462), agrees with the observed
opposite effects of o- and p-methoxy substitution. Observed data
for L5Naph suggest that extension of conjugation on the naph-
thol group yielded reduction in charge shift towards imidazole
ring. Experimental data suggest that the fused phenanthrene
group (L8tBuPt) on the 4,5-carbons of the imidazole behaved as
electron-withdrawing. While 4,5-diphenyl groups acted to a lesser
extent as electron-withdrawing, the 4,5-diethyl groups showed
electron-releasing character. The electron-withdrawing roles of the
phenanthreneyl and 4,5-diphenyl groups can be attributed to ␲-
interactions between the aromatic ␲-electrons of the substituents
and that of the imidazole ring. The optimized structure of the
4,5-diphenyl substituted compound (Fig. 4) revealed ␲-electron
delocalization over the C–C single bonds between imidazole ring
and the aromatic substituents at 4-, 5- and 2-positions. More-
over, optimized structure computation for L1Et showed a double
bond character between the 2-imidazole carbon and phenol rings.
In agreement with published X-ray structures of L1Et and L6Me

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tion constant values. The pKa values observed for the imidazole
nitrogen base ranged from 1.11 to 6.64 contrary to the general
believe that pKa values for imidazole nitrogen base is usually
around pKa = 6. The phenol hydroxyl functions in the studied
molecules showed lesser sensitivity to substituents effects unlike
the imidazole base. While electron-releasing substituents pro-
duced increase in protonation–deprotonation pKas for the hydroxyl
group, values for the imidazole base were mainly affected by polar-
ization of the imidazole ring aromaticity across the 2-imidazole
carbon to 4,5-imidazole carbons axis of the imidazole ring. There-
fore, it was concluded that electron-releasing substituents on
the phenol ring and/or electron-withdrawing substituents on 4,5-
imidazole carbons negatively affects donor strengths/coordination
chemistries of 2-(1H-imidazol-2-yl)phenols, and vice versa. Exper-
imental findings in this work also show that the substituents on the
phenol ring significantly affect the donor strength of the imidazole
base. The understanding of pKa variation on account of elec-
tronic effects of different substituents in this work should aid the
understanding of biochemical properties of imidazole-dependent
biomolecules. The nature of substituent functionalities in the envi-
ronments of imidazole donors present in biomacromolecules such
as metalloenzymes, nucleotides, etc., can also be predicted based
on ionization constant determinations.
Acknowledgements
Fig. 6. 1H NMR spectra for compounds L1Et, L6Me and L8tBuPt in deuterated chlo-
roform.
The authors thank the Chinese Academy of Sciences and the
Academy of Sciences for the Developing World (Italy) for grant-
ing postgraduate fellowship (CAS-TWAS) to AOE. The authors are
also grateful to Redeemer’s University – Nigeria for granting study
leave to AOE.
substituents and donor property of such imidazole base can be
predictable.
3.3. FTIR and 1H NMR spectral characteristics of active protons
The observed FTIR and 1H NMR data are presented in Table 1. The
imidazole (N–H) and the phenolic (O–H) protons, which are the two
types of active protons present in the investigated molecules, were
spectroscopically compared for potentially useful information
derivable from FTIR and 1H NMR data and that can aid under-
standing of substituent effects on protonation–deprotonation
equilibrium characteristics as well as intramolecular H-bonding
properties. Solid-state FTIR signals for the phenolic protons ꢀO–H
were generally weaker and very broad unlike the sharp peaks
found for the imidazole N–H peaks in all cases. Confirmation of
this conclusion was obtained from spectral overlay for L8tBuPt
and its oxazole analogue, which was obtained as a second prod-
uct in the synthesis of L8tBuPt (Fig. 4(a)) [36]. In fact, the O–H
signals for compound with relatively stronger imidazole donor
strengths (e.g. L2Ph, L3m-OMe, L4p-OMe and L5Naph; Fig. 4(b)
and (c)) were not observed, which is in agreement with weak-
ening of O–H vibrations as a result of stronger intramolecular
hydrogen bonding in such cases. The 1H NMR properties of the
molecules also provided support for observed trends. It is notable
that, under similar conditions, L8tBuPt gave very sharp signals
for the imidazole N–H and phenolic O–H protons (Fig. 5). This
suggests weak or absence of intramolecular H-bonding and low
donor strength of the imidazole base. Therefore, it could be con-
cluded that electron-releasing substituents on the phenol ring
and/or electron-withdrawing substituents on 4,5-imidazole car-
bons negatively affects donor strengths/coordination chemistries
of 2-(1H-imidazol-2-yl)phenols, and vice versa (Fig. 6).
References
[1] T.W. Birch, L.J. Harris, Biochem. J. 24 (1930) 564.
[2] J.P. Greenstein, J. Biol. Chem. 93 (1931) 479.
[3] G.M. Richardson, Biochem. J. 27 (1933) 1036.
[4] P.V. Oliferenko, A.A. Oliferenko, G. Poda, V.A. Palyulin, N.S. Zefirov, A.R.
Katritzky, J. Chem. Inf. Model. 49 (1999) 634.
[5] W.N. Lipscomb, N. Strter, Chem. Rev. 96 (1996) 2375.
[6] T.J. Meyer, M.H.V. Huynh, H.H. Thorp, Angew. Chem. Int. Ed. 46 (2007) 5284.
[7] M. Voicescu, Y. El Khoury, D. Martel, M. Heinrich, P. Hellwig, J. Phys. Chem. B
113 (2009) 13429.
[8] J.C. Freys, G. Bernardinelli, O.S. Wenger, Chem. Commun. 2008 (2008) 4267.
[9] T. Irebo, S.Y. Reece, M. Sjodin, D.G. Nocera, L. Hammarström, J. Am. Chem. Soc.
129 (2007) 15462.
[10] G.T. Castro1, S.E. Blanco, O.S. Giordano, Molecules 5 (2000) 426.
[11] T. Gladysheva, J. Liu, B.P. Rosen, J. Biol. Chem. 271 (1996) 33256.
[12] C. Ög˘retir, H. Berber, O. Asutay, J. Chem. Eng. Data 46 (2001) 1540.
[13] N.C. Marziano, C. Tortatoa, R. Bertani, J. Chem. Soc. Perkin Trans. 2 (1992) 955.
[14] J.L. Décout, M.C. Maurel, Orig. Life Evol. Biosph. 23 (1993) 299.
[15] G. Ataie, A.A. Moosavi-Movahedi, A.A. Saboury, G.H. Hakimelahi, J.R. Hwu, S.C.
Tsay, Int. J. Biol. Macromol. 27 (2000) 29.
[16] S. Yan, Y. Bu, J. Phys. Chem. 108 (2004) 13874.
[17] M.S.A. Hamza, X. Zou, R. Banka, K.L. Brown, R.v. Eldik, Dalton Trans. 2005 (2005)
782.
[18] H.-O. Bertrand, M.-O. Christen, J.-L. Burgot, Analyst 120 (1995) 2639.
[19] L. Benisvy, A.J. Blake, D. Collison, E.S. Davies, C.D. Garner, E.J.L. McInnes, J.
McMaster, G. Whittaker, C. Wilson, Chem. Commun. 2001 (2001) 1824.
[20] C. Foulon, C. Danel, C. Vaccher, S. Yous, J.-P. Bonte, J.-F. Goossens, J. Chromatogr.
A 1035 (2004) 131.
[21] Y.-X. Yan, Y.-H. Sun, L. Tian, H.-H. Fan, H.-Z. Wang, C.-K. Wang, Y.-P. Tian, X.-T.
Tao, M.-H. Jiang, Opt. Mater. 30 (2007) 423.
[22] K. Feng, F.-L. Hsu, D.V. DerVeer, K. Bota, X.R. Bu, J. Photochem. Photobiol. 165
(2004) 223.
[23] M.-J. Han, Y.-M. Chen, K.-Z. Wang, N. J. Chem. 32 (2008) 970.
[24] F. Gao, X. Chen, F. Zhou, L.-P. Weng, L.-T. Guo, M. Chen, H. Chao, L.-N. Ji, Inorg.
Chim. Acta 362 (2009) 4960.
[25] L. Bu, T. Sawada, Y. Kuwahara, H. Shosenji, K. Yoshida, Dyes Pigments 59 (2003)
43.
4. Conclusion
[26] J.A. Mondal, G. Ramakrishna, A.K. Singh, H.N. Ghosh, M. Mariappan, B.G. Maiya,
T. Mukherjee, D.K. Palit, J. Phys. Chem. 108 (2004) 7843.
[27] R.-Y. Wang, W.-L. Jia, H. Aziz, G. Vamvonuis, S. Wang, N.-X. Hu, Adv. Funct.
Mater. 15 (2005) 1483.
New imidazole based molecules were synthesized, character-
ized and used to investigate the effects of parameters such as
different substituents and intramolecular interactions on ioniza-
[28] W. Lin, L. Long, L. Yuan, Z. Cao, B. Chen, W. Tan, Org. Lett. 10 (2008) 5577.

A.O. Eseola, N.O. Obi-Egbedi / Spectrochimica Acta Part A 75 (2010) 693–701
701
[29] K.-Z. Wang, L.-H. Gao, G.-Y. Bai, L.-P. Jin, Inorg. Chem. Commun. 5 (2002) 841.
[30] A.O. Eseola, M. Zhang, J.-F. Xiang, W. Zuo, Y. Li, J.A.O. Woods, W.-H. Sun, Inorg.
Chim. Acta, doi:10.1016/j.ica.2009.1002.1026, in press.
[38] M.A. Ríos, M.C. Ríos, J. Phys. Chem. A 102 (1998) 1560.
[39] S. Yan, Y. Bu, Z. Cao, P. Li, J. Phys. Chem. A 108 (2004) 7038.
[40] J.S. Coleman, L.P. Varga, S.H. Mastin, Inorg. Chem. 9 (1970) 1015.
[31] Y.-P. Tong, S.-L. Zheng, X.-M. Chen, Eur. J. Inorg. Chem. 44 (2005) 3734.
[32] R.M. Tarkka, X. Zhang, S.A. Jenekhe, J. Am. Chem. Soc. 118 (1996) 9438.
[33] F. Liang, L. Wang, D. Ma, X. Jing, F. Wang, Appl. Phys. Lett. 81 (2002) 4.
[34] I.J. Rhile, T.F. Markle, H. Nagao, A.G. DiPasquale, O.P. Lam, M.A. Lockwood, K.
Rotter, J.M. Mayer, J. Am. Chem. Soc. 128 (2006) 6075.
[35] T.F. Markle, I.J. Rhile, A.G. DiPasquale, J.M. Mayer, Proc. Natl. Acad. Sci. 105
(2008) 8185.
[36] A.O. Eseola, W. Li, R. Gao, M. Zhang, X. Hao, T. Liang, N.O. Obi-Egbedi, W.-H. Sun,
Inorg. Chem. 48 (2009) 9133, and supporting information there in.
[37] K. Das, N. Sarkar, A.K. Ghosh, D. Majumdar, D.N. Nath, K. Bhattacharyya, J. Phys.
Chem. 98 (1994) 9126.
[41] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman,
V.G. Zakrzewski, J.A. Montgomery Jr., R.E. Stratmann, J.C. Burant, S. Drapprich,
J.M. Millam, A.D. Daniels, K.N. Kudin, M.C. Strain, O. Farkis, J. Tomasi, V. Barone,
M. Cossi, R. Cammi, B. Mennucci, C. Pomelli, C. Adamo, S. Clifford, J. Ochterski,
G.A. Petersson, P.Y. Ayala, Q. Cui, K. Morokuma, D.K. Malick, A.D. Rabuck, K.
Raghavachari, J.B. Foresman, J. Cioslowski, J.V. Ortiz, B.B. Stefanov, G. Lui, A.
Laishenko, P. Piskorz, I. Komoromi, R. Gomperts, R.L. Martin, D.J. Fox, T. Keith,
M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, C. Gonzalez, M. Challacombe, P.M.W.
Gill, B. Johnson, W. Chen, M.W. Wong, J.L. Andres, C. Gonzalez, M. Head-Gordon,
E.S. Repogle, J.A. Pople, GAUSSIAN 98, Revision A.6, Gaussian Inc., Pittsburgh,
PA, 1998.