New 1,6-heptadienes with pyrimidine bases attached: Syntheses and spectroscopic analyses

Article abstract of DOI:10.1016/j.molstruc.2007.08.026

A simple, high yielding synthesis leading to the functionalization of some pyrimidine bases with a 1,6-heptadienyl moiety spaced from the N - 1 position by a methylene group is described. A key step in this synthesis involves a Mitsunobu reaction by coupling ³N-benzoyluracil and ³N-benzoylthymine to 2-allyl-pent-4-en-1-ol followed by alkaline hydrolysis of the ³N-benzoyl protecting groups. This protocol should eventually lend itself to the synthesis of a host of N-alkylated nucleoside analogs. The absorption and emission properties of these pyrimidine derivatives (3-6) were studied in solvents of different physical properties. Computerized analysis and multiple regression techniques were applied to calculate the regression and correlation coefficients based on the equation that relates peak position λ_max to the solvent parameters that depend on the H-bonding ability, refractive index, and dielectric constant of solvents.

Full text of DOI:10.1016/j.molstruc.2007.08.026

Available online at www.sciencedirect.com
Journal of Molecular Structure 881 (2008) 11–20
www.elsevier.com/locate/molstruc
New 1,6-heptadienes with pyrimidine bases attached:
Syntheses and spectroscopic analyses
a,
a
b
Hassan H. Hammud *, Amer M. Ghannoum , Fares A. Fares ,
b
b,
*
Lara K. Abramian , Kamal H. Bouhadir
a
Chemistry Department, Faculty of Science, Beirut Arab University, Box 11-5020, Beirut, Lebanon
Chemistry Department, Faculty of Arts & Sciences, American University of Beirut, Box 11-0236, Beirut, Lebanon
b
Received 19 January 2007; received in revised form 21 August 2007; accepted 22 August 2007
Available online 4 September 2007
Abstract
A simple, high yielding synthesis leading to the functionalization of some pyrimidine bases with a 1,6-heptadienyl moiety spaced from
3
the N ꢀ 1 position by a methylene group is described. A key step in this synthesis involves a Mitsunobu reaction by coupling N-ben-
3
3
zoyluracil and N-benzoylthymine to 2-allyl-pent-4-en-1-ol followed by alkaline hydrolysis of the N-benzoyl protecting groups. This
protocol should eventually lend itself to the synthesis of a host of N-alkylated nucleoside analogs.
The absorption and emission properties of these pyrimidine derivatives (3–6) were studied in solvents of different physical properties.
Computerized analysis and multiple regression techniques were applied to calculate the regression and correlation coefficients based on
the equation that relates peak position kmax to the solvent parameters that depend on the H-bonding ability, refractive index, and dielec-
tric constant of solvents.
ꢀ 2007 Elsevier B.V. All rights reserved.
Keywords: Heptadiene; Uracil; Thymine; Mitsunobu reaction; Absorption spectra; Fluorescence
1. Introduction
and fluorescence spectra in different solvents and pH can
provide useful information because most laboratory exper-
iments as well as bio-processes occur in solution [10,11].
The ultraviolet absorption spectra of some purines and
pyrimidines had been studied during the last decades
[12–17]. Correlations found among the bands of pyrimidine
bases and some of their derivatives show that these bands
are simply derived from those of benzene [18]. Fluorescence
studies of some quinolines [19,20], 2-substituted pyrimi-
dines [21,22], 2-substituted purines [23], 5-substituted thi-
adiazolo and thiazolo pyrimidines [24,25] have been
reported. Recently, the electronic spectra of some barbitu-
ric and thiobarbituric acids were studied in different sol-
vents and pH, and a computerized analysis with multiple
regression techniques was applied [26]. Solvent effects on
the electronic absorption bands shift are commonly under-
stood as an indication of the extent of charge reorganiza-
tion of solute molecules upon electronic excitation.
Conversely, solvent shifts of emission bands reflect the
Synthetic oligodeoxynucleotides (ODNs) have gained
significant interest recently due to their increased role in
therapeutic and diagnostic applications [1–4]. Non-conju-
gated heptadienes have been polymerized and copolymer-
ized with a variety of monomers to yield polymers with
interesting properties [5–7]. One approach to synthetic neu-
tral ODNs is the polymerization of heptadienes with
nucleic bases attached. Incorporation of such modified,
unnatural nucleobases in oligonucleotides chain enables
the application of fluorescence techniques to nucleic acid
detection and to studies of conformation, dynamics and
interactions of bio-molecules [8,9]. The spectroscopic study
of these molecules in solution particularly their absorption
*
Corresponding authors. Tel.: +961 3 381862; fax: +961 1 300110.
E-mail addresses: hhammud@yahoo.com (H.H. Hammud), kb05@
aub.edu.lb (K.H. Bouhadir).
0022-2860/$ - see front matter ꢀ 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2007.08.026

12
H.H. Hammud et al. / Journal of Molecular Structure 881 (2008) 11–20
influence of equilibrium solvent arrangement around the
excited solute, rearranging inertially due to the instanta-
neous charge redistribution upon radiative deactivation
to the ground electronic state.
An effort is presented in this paper to synthesize and
characterize the spectral bands of some pyrimidines deriv-
atives and to correlate the wavelength shift (absorbance
and emission) in these compounds with the variation in sol-
vent properties and pH.
0 ꢁC (ice-water bath), a solution of acid 1 (13.6 g, 97 mmol)
in dry tetrahydrofuran (75 ml) was added drop-wise and
the mixture was refluxed for 21 h. The flask was then
cooled to room temperature and then immersed in an ice-
water bath. The reaction was quenched carefully with
water (6 ml), aqueous potassium hydroxide (15%, 6 ml),
and water (6 ml). The solution was filtered and the solid
washed with diethyl ether. The combined filtrate and
organic washes were dried over anhydrous magnesium sul-
phate and filtered. The solvent was evaporated under
reduced pressure to yield 2-allyl-pent-4-en-1-ol (12.0 g,
2. Equipments and reagents
1
98% yield). H NMR (300 MHz) d 1.6 (p, 1H), 2.0 (m,
Melting points were determined using a Fisher–Jones
4H), 2.8 (br s, 1H), 3.4 (br s, 2H), 4.9 (m, 4H), 5.7 (m,
2H); 13C NMR (75 MHz) d 35.0 (t), 40.0 (d), 64.6 (t),
116.1 (t), 136.6 (d). The spectroscopic data were in good
agreement with those reported in the literature [27,28].
1
apparatus. H NMR and 13C NMR spectra were recorded
in CDCl3 at 300 MHz (1H) or 75 MHz (13C) on a Bruker
AM300 NMR spectrometer. Chemical shifts are reported
in parts per million (d) downfield relative to tetramethylsil-
ane (TMS). Multiplicities were determined by DEPT exper-
iments. Infrared spectra were recorded as KBr pellets using
a Nicolet AVATAR 360 FTIR ESP spectrometer. The IR
bands are reported in wave numbers (m, cmꢀ1). Analytical
thin layer chromatography (TLC) was performed on Anal-
tech silica gel TLC Uniplates. Column chromatography
3.1.2. 1-(2-Allyl-pent-4-enyl)-3-benzoyl-1H-pyrimidine-2,4-
dione (3)
To a mixture of 3N-benzoyluracil (4.32 g, 20 mmol),
2-allyl-pent-4-en-1-ol (3.02 g, 24 mmol), and triphenyl phos-
phine (6.3 g, 24 mmol) in dry dioxane (130 ml) at 0 ꢁC was
added drop-wise a solution of diisopropyl azodicarboxylate
(DIAD, 94%, 5.16 g, 24 mmol) in dry dioxane (30 ml) under
a nitrogen atmosphere over 30 min. The mixture was stirred
at room temperature overnight to yield a clear solution. The
solvent was evaporated under reduced pressure to give an
oily residue from which some triphenylphosphine oxide
and diisopropyl hydrazodicarboxylate crystallized over-
night. The solid was filtered and washed with a small amount
of diethyl ether. The filtrates were combined and concen-
trated under reduced pressure and the residue was purified
by column chromatography using dichloromethane:acetone
(9:1) to yield the 1-(2-allyl-pent-4-enyl)-3-benzoyl-1H-
pyrimidine-2,4-dione as a white solid (4.47 g, 69% yield).
˚
was performed with ACROS silica gel (60 A, 200–400
mesh). Chemicals and reagents used in the various synthe-
ses were purchased from the Aldrich Chemical Company
(Milwaukee, WI) and ACROS Organics (Belgium), and
were used as received. 1,4-Dioxane and tetrahydrofuran
were purchased from ACROS Organics, dried over sodium
metal, and then distilled directly before use.
The pH of solutions was measured on GP 353 ATC pH-
meter after calibration with buffer solutions at pH’s 4 and
7. The electronic absorption spectra were recorded at 25 ꢁC
on SP-3000 OPTIMA UV–Visible spectrophotometer,
Japan. The room temperature spectrofluorometric mea-
surements were carried out on a Jasco FP-6200 spectroflu-
orometer, Japan and supported with Jasco spectra
manager software for Jasco corporation version 1.05.
The measured fluorescence intensity of the solution of
compounds in different solvents was not subtracted from
that of the corresponding pure solvent. The intensity scale
is thus an arbitrary scale.
1
M.p. 74–75 ꢁC; H NMR (300 MHz) d 2.1 (m, 5H), 3.66
(d, J = 3.9 Hz, 2H), 5.09 (m, 4H), 5.75 (m, 2H), 5.79 (d,
J = 7.95 Hz, 1H), 7.21 (d, J = 7.98 Hz, 1H), 7.52 (m, 2H),
7.64 (m, 1H), 7.92 (m, 2H); 13C NMR (75 MHz) d 35.6 (t),
36.8 (d), 52.8 (t), 101.8 (d), 117.7 (t), 129.2 (d), 130.4 (d),
131.4 (s), 135.1 (d), 144.8 (d), 149.9 (s), 162.4 (s), 168.7 (s);
FTIR (KBr disk, cmꢀ1) 3099, 3072, 2974, 2928, 1749, 1697,
1652, 1624, 1595, 1446, 1384, 1338, 1350, 1255, 1105, 978,
918, 804, 783, 763, 700, 680, 630; HRMS (EI) calcd for
C19H20N2O3 (M+), 324.14739, found 324.14751.
The electronic spectra of the solution (concentration
1 · 10ꢀ5 to 1 · 10ꢀ6 mol/l) were investigated in various
organic solvents of spectroscopic grade. The solvents are
of different polarities: carbon tetrachloride (CCl4), diethyl
ether, 1,4-dioxane, chloroform (CHCl3), N,N-dimethyl-
formamide (DMF), dimethyl sulfoxide (DMSO), acetoni-
trile (CH3CN), ethanol (EtOH), and methanol (MeOH).
3.1.3. 1-(2-Allyl-pent-4-enyl)-1H-pyrimidine-2,4-dione (4)
To a solution of sodium metal (0.75 g, 32.6 mmol) in
methanol (35 ml) at 0 ꢁC (ice-water bath) under a nitrogen
atmosphere was added drop-wise a solution of 3 (1.08 g,
3.33 mmol) in methanol (20 ml) and the mixture was
refluxed for 4 h then stirred at room temperature over-
night. The solvent was evaporated under reduced pressure
and the residue was dissolved in dichloromethane (20 ml)
and washed with aqueous hydrochloric acid (10%, 10 ml)
and then with aqueous saturated solution of sodium bicar-
bonate (10 ml). The organic layer was dried over anhy-
3. Synthesis of the pyrimidine derivatives
3.1. Method of preparation
3.1.1. 2-Allyl-pent-4-en-1-ol (2)
To a stirred suspension of lithium aluminum hydride
(5.8 g, 95%, 146 mmol) in dry tetrahydrofuran (60 ml) at

H.H. Hammud et al. / Journal of Molecular Structure 881 (2008) 11–20
13
drous magnesium sulphate, filtered, and the solvent was
removed under reduced pressure to yield a white solid that
was purified by flash chromatography using dichlorometh-
ane: acetone (9:1) to afford 4 as a white solid (623 mg, 85%
yield). M.p. 87–88 ꢁC; 1H NMR (300 MHz) d 2.10 (m, 5H),
3.65 (d, 2H, J = 6.03 Hz), 5.10 (m, 4H), 5.73 (d,
J = 7.86 Hz, 1H), 5.79 (m, 2H), 7.13 (d, J = 7.86 Hz,
1H), 10.0 (br. s, NH); 13C NMR (75 MHz) d 35.4 (t),
36.9 (d), 52.2 (t), 101.9 (d), 117.5 (t), 135.1 (d), 145.0 (d),
151.3 (s), 164.2 (s); FTIR (KBr disk, cmꢀ1) 3016.5, 2978,
2916, 1701, 1670, 1464, 1406, 1387, 1360, 1340, 1279,
1248, 1232, 1178, 993, 916, 767, 551; HRMS (EI) calcd
for C12H16N2O2 (M+), 220.12118, found 220.11989.
matography using dichlromethane:acetone (9:1) to yield 6
as a white solid (1.52 g, 78% yield). M.p. 111–113 ꢁC; H
1
NMR (300 MHz) d 1.92 (s, 3H), 2.09 (m, 5H), 3.63 (d,
J = 6.12 Hz, 2H), 5.08 (m, 4H), 5.75 (m, 2H), 6.98 (s,
1H), 10.3 (br. s, NH); 13C NMR (75 MHz) d 12.3 (q),
35.4 (t), 37.1 (d), 51.8 (t), 110.4 (d), 117.2 (t), 135.5 (d),
141.0 (s), 151.6 (s), 164.9 (s); FTIR (KBr disk, cmꢀ1
)
3161, 3022, 2982, 2835, 1660, 1477, 1456, 1427, 1379,
1367, 1348, 1313, 1279, 1246, 1115, 993, 945, 914, 889,
862, 764, 563; HRMS (EI) calcd for C13H18N2O2 (M+),
234.13683, found 234.13649.
3.2. Results and discussion
3.1.4. 1-(2-Allyl-pent-4-enyl)-3-benzoyl-5-methyl-1H-
pyrimidine-2,4-dione (5)
We report herein, the synthesis of 1,6-heptadienes with
uracil and thymine connected to carbon-4 of the former
via a methylene spacer. The synthetic protocol was initi-
ated with the 2-allyl-pent-4-enoic acid 1 that was prepared
in our laboratory following a reported procedure [29].
Reduction of compound 1 to the corresponding primary
alcohol, 2-allyl-pent-4-en-1-ol 2, was achieved with lithium
aluminum hydride (LAH) in 98% yield [27,28] (Scheme 1).
To a mixture of 3N-benzoylthymine (4.6 g, 20 mmol), 2-
allyl-pent-4-en-1-ol (3.02 g, 24 mmol), and triphenyl phos-
phine (6.3 g, 24 mmol) in dry dioxane (130 ml) at 0 ꢁC was
added drop-wise a solution of diisopropyl azodicarboxy-
late (DIAD, 94%, 5.16 g, 24 mmol) in dry dioxane
(30 ml) under a nitrogen atmosphere over 30 minutes.
The mixture was stirred at room temperature overnight
to yield a clear solution. The solvent was evaporated under
reduced pressure to give an oily residue from which some
triphenylphosphine oxide and diisopropyl hydrazodicarb-
oxylate crystallized overnight. The solid was filtered and
washed with a small amount of diethyl ether. The filtrates
were combined and concentrated under reduced pressure
and the residue was purified by column chromatography
using dichloromethane:acetone (9:1) to afford 1-(2-allyl-
pent-4-enyl)-3-benzoyl-5-methyl-1H-pyrimidine-2,4-dione
as a white solid (5.2 g, 77% yield). M.p. 84–85 ꢁC; 1H NMR
(300 MHz) d 1.93 (s, 3H), 2.1 (m, 5H), 3.63 (d, J = 4.6 Hz,
2H), 5.09 (m, 4H), 5.78 (m, 2H), 7.08 (s, 1H), 7.47 (m, 2H),
7.64 (m, 1H), 7.89 (m, 2H); 13C NMR (75 MHz) d 12.1 (q),
35.2 (t), 36.8 (d), 52.1 (t), 109.8 (d), 117.3 (t), 129.2 (d),
130.2 (d), 131.5 (s), 135.4 (d), 141.4 (s), 149.9 (s), 163.1
(s), 169.3 (s); FTIR (KBr disk, cmꢀ1) 3072, 2974, 2927,
1745, 1697, 1647, 1599, 1442, 1345, 1321, 1225, 1115,
980, 956, 908, 875, 789, 762, 675; HRMS (EI) calcd for
C20H22N2O3 (M+), 338.16304, found 338.16295.
3
The N-protected uracil and thymine bases have been pre-
pared following reported procedures [30]. The Mitsunobu
reaction was then employed to couple the 3N-protected
nucleic bases to 2-allyl-pent-4-en-1-ol 2 utilizing triphenyl-
phosphine and diisopropyl azodicarboxylate (DIAD) in
dry dioxane to yield the heptadiene derivatives 3 and 5 in
69% and 77% yield, respectively [31–34].
Examination of the 1H NMR spectra of 3 and 5 revealed
the aromatic protons of the benzoyl group resonating in the d
7.5–8.0 ppm region. Further evidence for the formation of 3
and 5 was clearly indicated in the 13C NMR spectra by the
absence of the carbon resonating at d 65.1 ppm (carbon sin-
gly connected to an oxygen) and the presence of a less
deshielded carbon resonating at d 52.8 ppm and d
52.1 ppm in the spectrum of 3 and 5, respectively, indicating
carbons singly connected to the less electronegative nitrogen.
The 3N-benzoyl groups of intermediates 3 and 5 were then
hydrolyzed in a methanolic solution of sodium methoxide to
yield the target compounds 1-(2-allyl-pent-4-enyl)-1H-pyrim-
idine-2,4-dione 4 and 1-(2-allyl-pent-4-enyl)-5-methyl-1H-
pyrimidine-2,4-dione 6 in 85% and 78% yield, respectively
(Scheme 1). The formation of 4 and 6 was clearly elucidated
in the 1H NMR spectra by the two broad singlets at
10.0 ppm (for 4) and 10.2 ppm (for 6) due to the NH protons
in the heterocyclic ring. This was confirmed further by the
absence of signals for the aromatic protons resonating in the
d 7.5–8.0 ppm region in the 1H NMR spectra of both 4 and 6.
3.1.5. 1-(2-Allyl-pent-4-enyl)-5-methyl-1H-pyrimidine-2,4-
dione (6)
To a solution of sodium metal (1.88 g, 81.5 mmol) in
methanol (85 ml) at 0 ꢁC (ice-water bath) under a nitrogen
atmosphere was added drop-wise a solution of 5 (2.82 g,
8.33 mmol) in methanol (50 ml) and the mixture was
refluxed for 4 h then stirred at room temperature over-
night. The solvent was evaporated under reduced pressure
and the residue was taken up in dichloromethane (40 ml)
and washed with aqueous hydrochloric acid (10%, 20 ml)
and then with saturated solution of sodium bicarbonate
(20 ml). The organic layer was dried over anhydrous mag-
nesium sulphate. Removal of the solvent under reduced
pressure gave a white solid that was purified by flash chro-
4. UV absorption and fluorescence study of the pyrimidine
derivatives (3–6)
4.1. Method of calculations
The solvent effect and that of the specific interaction
between solute and solvent molecules (hydrogen bonding)

14
H.H. Hammud et al. / Journal of Molecular Structure 881 (2008) 11–20
O
O
N
O
N
BzN
O
BzN
O
HN
N
H
O
NaOMe
MeOH
CO2H
OH
LiAlH4
THF
3 (69%)
4 (85%)
O
HN
N
O
1
2 (98%)
O
BzN
BzN
O
N
O
O
N
NaOMe
MeOH
H
5 (77%)
6 (78%)
Scheme 1.
are major factors to explain the spectral behaviour of com-
pounds. In the regression analysis, the following equation
is used:
eters or three parameters. The results are listed in Tables
4–11.
In a complementary study the coefficients K1, K2, m
vapour were calculated using multiple regression technique
based on the following equation:
Y ¼ a0 þ a1X1 þ a2X2 þ a3X3 þ ꢁ ꢁ ꢁ
msolution ¼ mvapour þ K1ð2D ꢀ 2Þ=ð2D þ 1Þ þ K2ð2n2 ꢀ 2Þ=ð2n2 þ 1Þ
The constant a1, a2, and a3 are the different regression coef-
ficients, and the constant a0 is the regression intercept. The
observed peak location kmax (Y) is considered as the depen-
dent variable while the independent variables have been se-
lected to be the solvent interaction mechanisms (D, n, E)
and (E, K, M, N) (Table 1).
mvapour is the frequency of the maximum in absence of sol-
vents. D is the dielectric constant, and n is the refractive in-
dex of the solvents. As an indication of the goodness of the
fit, the multiple correlation coefficient and the square of
correlation were calculated for each r2(m, n2), and r2(m,
D); the results are summarized in Table 12. The emission
spectra were recorded in different solvents, and the Stokes
shift is correlated with the orientation polarizability Df
(function of dielectric constant D and refractive index n)
of the solvents.
The parameter E is an empirical solvent polarity param-
eter sensitive to both solvent–solute hydrogen bonding and
dipolar interactions. K depends on the solvent dielectric
constant D, and is a measure of the polarity of the solvent,
K = (D ꢀ 1)/(2D+1).
M depends on the solvent refractive index n and is a
measure of solute permanent dipole–solvent induced
dipole interactions, M = (n2 ꢀ 1)/ (2n2 + 1).
N
is
a
4.2. Results and discussion
measure of permanent dipole–permanent dipole interac-
tions, N = (D ꢀ 1)/(D + 2) ꢀ (n2 ꢀ 1)/(n2 + 2). A multiple
regression analysis has been performed; in each case fits
are obtained as a function of one parameter, two param-
The electronic absorption (Table 2 and Figs. 1, 2) and
fluorescence emission (Table 3 and Figs. 4–6) spectra for
each compound were recorded in a variety of solvents of
Table 1
Table 2
Solvent dielectric constant D, refractive index n, empirical polarity E, and
parameters used in spectral correlation equations
kmax(abs) of compounds (3–6) in solvents of different polarities
Solvents
Compound
Compound
Compound
Compound
Solvent
D
n
E
K
M
N
3
4
5
6
CCl4
2
4.2
2.2
1.426
1.353
1.422
1.443
1.33
1.427
1.478
1.344
1.361
1.329
32.5
34.6
36
39.1
63.1
43.8
45
46
51.9
55.5
0.2
0.22
0.18
0.2
0.21
0.17
0.2
0.22
0.18
0.18
0.17
0.01
0.3
CCl4
Ether
Dioxane
261, 277
252, 280
255, 279
268
265
267
269
272
270
268
269
269
262, 283
250, 282
255, 283
256, 284
271
274
270
272
275
275
275
273
274
274
Diethyl ether
1,4-Dioxane
Chloroform
Water
Dimethylformamide
Dimethyl sulfoxide
Acetonitrile
Ethanol
0.34
0.22
0.36
0.49
0.48
0.49
0.48
0.47
0.48
0.03
0.29
0.76
0.67
0.66
0.71
0.67
0.71
4.7
Chloroform 256, 280
78.5
36.7
48.9
37.5
24.3
32.6
DMF
DMSO
270
264
264
Acetonitrile 255, 278
254, 280
254, 283
255, 283
Ethanol
Methanol
255, 280
255, 280
Methanol

H.H. Hammud et al. / Journal of Molecular Structure 881 (2008) 11–20
15
Fig. 1. Electronic absorption spectra of 3 in different solvents: (a) methanol, (b) ethanol, (c) acetonitrile, (d) chloroform, (e) 1,4-dioxane, (f) diethyl ether,
and (g) carbon tetrachloride.
different physical properties, mainly the dielectric constant
(e) and the refractive index (n). Generally, the effect of sol-
vents on the absorption bands of these substances consists
of displacements and does not involve a fundamental
change of the general form of the spectrum [35–38]. The
absorption and emission spectra of these compounds are
perturbed by varying the organic solvents, and the spectral
shifts are different for the absorption spectrum from those
for the emission one.
to p–p* electronic transitions and exhibit red shift (com-
pound 4, Table 2) as proceeding from non-polar (CCl4,
k
max = 268 nm) to polar solvents (DMF, kmax = 272 nm)
due to the stabilization of p* orbital more than p orbital.
Also, the first band (Band A) in the range 250–272 nm
(compounds 3 and 5) exhibit p–p* electronic transitions
with high molar absorptivities and bathochromic shift
while proceeding from CCl4 (kmax = 261 nm) and diethyl
ether (kmax = 252 nm) to the more polar solvents DMF
(kmax = 270 nm) and DMSO (kmax = 264 nm) (compound
3, Table 2) that substantiate their p–p* nature. The band
(Band B) at about 280 nm (compounds 3 and 5) is associ-
ated with considerable intramolecular charge transfer char-
acter [39,40] whose nature is substantiated by its broadness
4.2.1. Spectrophotometric study
4.2.1.1. Absorption electronic spectra. The electronic
absorption spectra of compounds 4 and 6 show strong
absorption band (Band A) in the range 265–275 nm due
Fig. 2. Electronic absorption spectra of 4 in different solvents: (a) methanol, (b) ethanol, (c) acetonitrile, (d) chloroform, (e) 1,4-dioxane, (f) carbon
tetrachloride, and (g) diethyl ether.

16
H.H. Hammud et al. / Journal of Molecular Structure 881 (2008) 11–20
Table 3
k
dielectric constant and refractive index of solvent as well
as H-bond interaction.
abs, kem, Dm(cmꢀ1) for compounds (3–6) and Df values in different solvents
Solvent
Compound
kabs
kem
Dm
Df
A one parameter correlation between kmax of com-
pounds 3–6 with either D, n, or E parameters reveal a high
dependence of kmax (compounds 3 and 5) on the refractive
index with MCC > 0.6 compared to that of 4 and 6 with
MCC < 0.5. The correlation for E parameter with kmax in
case of compound 3 and 5 indicate no remarkable solute–
solvent hydrogen bond interaction (MCC < 0.03) com-
pared to that of 4 and 6 with MCC > 0.4 indicating
solute–solvent hydrogen bonding interactions present
along with dipole interactions.
Correlation with two parameters equation for hydro-
gen bonding and refractive index (MCC > 0.8) prove
higher influence of these two parameters on the position
of kmax for compounds 4 and 6 than that of the dielectric
constant and hydrogen bonding (MCC = 0.645) or
dielectric constant and refractive index (MCC = 0.763)
(Tables 5–7).
The correlations for compounds 3 and 5 show no
remarkable solute–solvent hydrogen bonding interactions
compared to compounds 4 and 6 due to the presence of
the benzoyl group at the N(3) position that substituted
the amino (NH) hydrogen atom, but a (D, n) interaction
with correlation of (MCC = 0.784 and 0.763) for 3 and 5,
respectively (Tables 4–6). Little improvement of fits was
shown when using three parameters D, n, and E in case
of compounds (4–6) indicating their influence in different
manner.
Diethyl ether
3
4
5
6
3
4
5
6
3
4
5
6
3
4
5
6
3
4
5
6
3
4
5
6
3
4
5
6
3
4
5
6
252
265
250
270
255
267
255
272
256
269
256
275
270
272
271
275
264
270
264
275
255
268
254
273
255
269
254
274
255
269
255
274
343
305
345
311
311
303
313
307
359
335
360
336
328
329
329
332
326
330
326
335
313
10528
0.162
4948.96
11014.5
4882.7
7061.3
4449.8
7266.8
4191.4
11207.3
7323.9
11284.7
6601.7
6549.2
6369.5
6505.2
6243.15
7203.9
6734.0
7203.9
6512.3
7266.8
Dioxane
CHCl3
0.02
0.148
0.274
0.263
0.305
0.289
0.309
DMF
DMSO
CH3CN
Ethanol
Methanol
313
7421.2
323
326
322
330
8255.9
6499.8
8314.1
6193.3
332
339
9095.2
6997.8
The correlations between kmax of compounds (3–6) with
eitherE(solventpolarityparameter),K(functionofdielectric
constant), M (function of refractive index), or N (measure of
permanentdipole–permanentdipoleinteraction)parameters
(Tables 8–11) show dependence of kmax of compound 3 on M
parameter (MCC > 0.5), and that of compound 5 on K
parameter (MCC > 0.5), but relatively similar dependence
of kmax of compounds 4 and 6 on each parameter.
Higher correlation is shown in compound 3 using two
parameters equation (Table 8) with either (KM, MCC =
0.759) or (MN, MCC = 0.785) than with (EM, MCC =
0.686), (EN, MCC = 0.436) or (KN, MCC = 0.238)
parameters.
Table 4
Regression analysis for compound 3 at kabs = 255 nm using D, n, and E
solvent parameters
Parameters
a0
a1
0.146
69.129
ꢀ0.007
0.148
0.305
0.239
ꢀ0.18
a2
a3
MCC
D
254.984
161.461
258.424
154.453
273.798
129.288
180.192
0.466
0.626
0.01
0.784
0.679
0.691
0.796
n
E
D, n
D, E
n, E
D, n, E
69.725
ꢀ0.521
36.261
58.108
0.203
Compound 5 show higher correlation (Table 10)
between kmax and KM, KN or EK, with a MCC > 0.7 show-
ing a more influence of the polarity parameter on the spec-
tra than in case of compound 3.
Compounds 4 and 6 show high correlation (Tables 9 and
11) between the parameter K and the N parameter
(MCC > 0.79) or the E parameter (MCC > 0.8); improve-
ment of fits when using three parameters E, K, and M or
N since higher correlation coefficients (MCC > 0.8) are
obtained.
and its sensitivity to the nature of solvent used and is con-
firmed by its spectral behaviour in buffer solution of differ-
ent pH values.
The absence of the n–p* in the spectra of these com-
pounds can be presumably ascribed to its submerging with
a strong (280 nm) intramolecular charge transfer band (3,
5) and of the p–p* band (4, 6).
4.2.1.2. Solvatochromism absorption correlation studies.
From the correlation of kmax (Band A) for compounds 3–6
with any of solvent parameters, an idea about the type of
interactions between the solute and solvent can be
obtained. The solvatochromic shift reveals the effect of
The values of K1, K2, m (vapour), r2 (m, D), r2 (m, n) and
MCC for solutes are computed and listed in Table 12. The
data indicated that both the dielectric constant and the
refractive index of solvents affect the electronic absorption
spectra of compounds but with varying degree.

H.H. Hammud et al. / Journal of Molecular Structure 881 (2008) 11–20
17
Table 5
Table 8
Regression analysis for compound 4 at kabs = 269 nm using D, n, and E
solvent parameters
Regression analysis coefficients for compound 3 at kabs = 255 nm using E,
K, M, and N
Parameters
a0
a1
0.068
15
0.118
0.069
0.066
a2
a3
MCC
a0
a1
a2
a3
MCC
D
267.094
247.584
263.505
245.726
266.812
220.628
225.836
0.644
0.402
0.478
0.763
0.645
0.83
E
258.424
253.813
223.85
256.27
263.51
194.015
274.404
199.933
247.773
201.587
202.223
277.453
210.733
213.253
ꢀ0.07
0.01
n
K
M
10.99
175.197
4.091
0.223
0.572
0.209
0.417
0.686
0.436
0.759
0.238
0.785
0.76
E
D, n
D, E
n, E
D, n, E
15.276
0.008
0.2
N
EK
ꢀ0.466
37.041
254.405
17.045
243.569
ꢀ11.461
11.858
28.173
25.437
EM
EN
KM
KN
MN
EKM
EKN
EMN
KMN
0.336
0.157
0.021
0.839
ꢀ0.561
26.967
39.619
261.754
ꢀ0.05
Table 6
29.397
237.928
21.991
15.595
49.201
Regression analysis for compound 5 at kabs = 254 nm using D, n, and E
solvent parameters
ꢀ0.579
ꢀ0.182
ꢀ92.198
ꢀ11.564
246.124
300.289
0.437
0.793
0.819
Parameters
a0
a1
0.15
a2
a3
MCC
D
254.671
145.888
258.667
141.756
274.828
110.229
158.901
0.424
0.641
0.022
0.772
0.632
0.702
0.778
n
80.109
ꢀ0.18
0.153
0.321
0.264
0.194
E
Table 9
D, n
D, E
n, E
D, n, E
80.723
Regression analysis coefficients for compound 4 at kmax = 269 nm using E,
K, M, and N
ꢀ0.558
97.535
71.964
a0
a1
a2
a3
MCC
ꢀ0.135
E
263.505
262.858
264.919
266.941
242.333
264.701
266.718
250.932
252.191
263.2
0.118
0.478
0.282
0.559
0.544
0.821
0.559
0.544
0.79
0.813
0.563
0.845
0.85
K
M
29.134
9.299
3.587
0.231
0.01
0.007
63.227
70.609
17.466
0.15
Table 7
N
EK
Regression analysis for compound 6 at kabs = 274 nm using D, n, and E
solvent parameters
83.626
EM
EN
KM
KN
MN
EKM
EKN
EMN
KMN
8.716
3.427
Parameters
a0
a1
0.043
a2
a3
MCC
13.447
5.682
D
272.624
251.618
269.89
250.427
271.668
229.733
226.019
0.479
0.49
n
15.691
0.086
0.044
0.035
0.162
0.193
ꢀ3.261
80.185
82.063
20.869
ꢀ16.582
E
0.404
0.689
0.487
0.845
0.851
244.047
245.488
261.215
254.289
6.14
D, n
D, E
n, E
D, n, E
15.868
0.026
26.386
28.337
0.133
0.039
77.589
2.944
ꢀ5.498
12.398
0.568
0.822
ꢀ0.015
4.2.1.3. pH effect on absorption spectra. The effect of pH
change on the electronic absorption spectra of solutions
of each of the compounds (3, 4, 5, and 6) was studied in
ethanol by adding 1 ml of universal buffer in the pH range
3.2–12 and the extreme pH (1.4 and 13.2) were obtained by
adding few drops of aqueous HCl (0.1 N) or aqueous
NaOH (0.1 N), respectively. The absorption spectra of
these compounds in different buffers show little shift in
Table 10
Regression analysis coefficients for compound 5 at kabs = 254 nm using E,
K, M, and N
a0
a1
a2
a3
MCC
E
258.667
217.315
254.192
256.307
183.226
263.339
273.43
192.781
194.137
248.898
190.179
198.272
277.181
209.028
ꢀ0.18
0.022
0.599
0.17
0.159
0.71
0.339
0.357
0.751
0.771
0.181
0.752
0.778
0.359
0.821
K
M
207.48
9.452
N
EK
3.515
0.384
297.98
k
max(abs), (Table 13, Fig. 3).
EM
EN
KM
KN
MN
EKM
EKN
EMN
KMN
ꢀ0.439
ꢀ0.53
177.615
297.595
34.547
0.057
ꢀ0.82
ꢀ0.551
347.141
34.026
15.746
27.662
All four compounds show red shift in kmax(abs) as pro-
ceeding from ethanolic solution to pH = 1.4; this red shift
is due to the protonation of non-bonded pair on carbonyl
group causing stabilization of the excited state relative to
the ground state (protonation at an amino group cause a
blue shift upon protonation) [41,42].
Compounds 3 and 5 show further red shift as proceeding
to basic solutions indicating a greater degree of interaction
between the substituents and the aromatic ring [13]. The
blue shift in the absorption spectra of compounds 4 and
6 in basic solutions could be due to the formation of differ-
ent tautomeric forms [43] also could be related to acid base
equilibrium.
12.346
ꢀ10.046
284.024
290.528
ꢀ14.227
ꢀ117.695
24.901
14.035
21.831
60.016
4.2.2. Fluorescence study
4.2.2.1. Fluorescence measurements. Compounds (3–6) fluo-
resce at room temperature [44–46]. The excitation wave-
length was fixed at 254 nm for compounds (3 and 5),

18
H.H. Hammud et al. / Journal of Molecular Structure 881 (2008) 11–20
Table 11
4.2.2.2. Solvent effect on the fluorescence properties. The
fluorescence emission spectra showed considerable spectral
shifts in the organic solvents (Table 3, Figs. 4–6). The spec-
tral shift is correlated with the polarity parameters (dielec-
tric constant and refractive index) of the solvents. Stokes
shift (ma ꢀ mem), is one of the quantitative parameters which
is useful to understand the origin of the variation of spec-
tral shift in organic solvents.
The large Stokes shift (Table 3) indicated an increase in
the dipole moment upon excitation. This behaviour has
been attributed to a charge redistribution of the excited
state with respect to the ground state.
The plots of (ma ꢀ mem) versus the solvent polarity
parameter Df for the compounds (3–6) in solvents of
different polarities (Df = [(D ꢀ 1)/(2D + 1) ꢀ (n2 ꢀ 1)/
(2n2 + 1)]) show the presence of linear correlation of Stokes
shift with Df in polar and non-polar solvents (r2 > 0.85) for
compounds (4 and 6) with a slight deviation in chloroform
(r2 = 0.65), but only a satisfactory linear relationship in the
aprotic (r2 > 0.9) solvents for compounds (3 and 5). The
plots show linear correlation that is in good agreement with
Lippert–Mataga equation [47–49] and confirms that the
slope depends upon the change in dipole moment upon
excitation.
Regression analysis coefficients for compound 6 at kabs = 274 nm using E,
K, M, and N
a0
a1
a2
a3
MCC
E
269.89
265.78
0.086
0.404
0.448
0.395
0.369
0.913
0.418
0.406
0.775
0.792
0.424
0.913
0.913
0.5
K
M
39.764
5.633
2.089
0.205
0.052
0.072
64.826
70.219
21.328
0.206
0.208
0.121
75.107
271.353
272.616
247.611
270.26
270.292
257.013
257.946
268.041
247.574
247.514
261.855
259.415
N
EK
87.999
EM
EN
KM
KN
MN
EKM
EKN
EMN
KMN
2.698
0.429
9.885
4.172
ꢀ6.284
88.073
88.047
31.997
ꢀ11.611
ꢀ0.132
ꢀ0.9
ꢀ13.256
8.875
0.798
while that of (4 and 6) at 269 nm. The shape of the excita-
tion spectrum is shown to coincide reasonably well with the
absorption spectrum. The fluorescence excitation spectra
were measured on samples with maximum absorbance less
than 0.1 in order to avoid inner filter distortion.
The emission wavelength (kmax) measured in different
solvents are shown in Table 3. Compound 3 show a hyp-
sochromic shift (Fig. 4) in kem while proceeding from
diethyl ether (343 nm) to DMF (328 nm) and DMSO
(326 nm) that validates an n–p* transition. The same
was noticed in case of compound 5 where emissions at
360 nm in chloroform and 345 nm in diethyl ether show
a blue shift (Table 3) to 326 nm in DMSO and 329 nm in
DMF. Compounds (3 and 5) show no fluorescence in
CCl4 due most probably to that this non-polar solvent
cannot form a hydrogen-bonded complex with the sol-
utes [25].
ꢀ
ꢁ
2ðle ꢀ lgÞ
ðD ꢀ 1Þ
ðn2 ꢀ 1Þ
ðma ꢀ memÞ ¼
2 ꢂ
ꢀ
þ K
hca3
ð2D þ 1Þ ð2n2 þ 1Þ
‘‘ma’’ and ‘‘mem’’ are the peak absorption and emission fre-
quencies per centimeter, ‘‘le’’ and ‘‘lg’’ are the dipole mo-
ment of each compound in excited and ground state, ‘‘D’’
and ‘‘n’’, are the dielectric constant and refractive index
of the solvent, respectively, ‘‘h’’ is the Planck’s constant,
‘‘c’’ is the speed of light and ‘‘a’’ the Onsager cavity radius
for each molecule, ‘‘K’’ is a constant.
Compounds 4 and 6 show a red shift in emission spec-
tra (Figs. 5 and 6) as proceeding from diethyl ether (305
and 311 nm, respectively) to DMF (329 and 332 nm,
respectively) and DMSO (330 and 335 nm, respectively),
due to p–p* transition [22]. Fluorescence quenching in
acetonitrile (compounds 4 and 6) is observed due to lone
pair donor–acceptor interaction. No fluorescence was
observed in CCl4 (compound 4 and 6) because the lowest
excited singlet state is of the n–p* type and favours radi-
ationless intersystem crossing as a mode of deactivation
of the lowest excited singlet state. The addition of small
amounts of acid results in hydrogen bonding with the
non-bonded pairs raising the energy of the n–p* state to
such a degree that the lowest p–p* state becomes the low-
est excited singlet state making fluorescence to occur [25].
4.2.2.3. pH effect. The emission spectra of these compounds
show little dependence of the position of kmax (emission) on
the pH of solution, but show slight enhancement of the
fluorescence intensity at low pH due to the formation of
cationic species, and of quenching at pH greater than 7
due to the formation of anionic species with non-fluoresc-
ing properties.
5. Conclusion
In summary, we have synthesized two examples of
non-conjugated dienes with uracil and thymine attached
and separated from carbon-4 of the former by a
methylene spacer. This protocol constitutes a simple,
Table 12
K1, K2, m(vapour), and correlation analysis data for the compounds (3–6) at different m (cmꢀ1
)
Compound
m(vap) (cmꢀ1
)
K1
K2
MCC
r2(m, D)
r2(m, n)
3
4
5
6
46688.35
40436.85
47636.95
38492.19
ꢀ1531.03
ꢀ1954.5
ꢀ17373.4
ꢀ3901.37
ꢀ19761.2
ꢀ3907.39
0.749
0.7
0.737
0.72
0.217
0.343
0.179
0.229
0.4
0.002
0.421
0.238
ꢀ1511.64
ꢀ539.356

H.H. Hammud et al. / Journal of Molecular Structure 881 (2008) 11–20
19
Table 13
max(abs) of compounds (3–6) in different pH
k
pH
ETOH
pH 1.4
pH 3.2
pH 5.1
pH 7.4
pH 9.7
pH 12.5
pH 13.2
Compound 3
Compound 4
Compound 5
Compound 6
255
269
254
274
256
270
256
275
256
270
256
275
256
270
256
275
256
270
256
275
257
269
257
274
257
268
257
273
260
267
258
273
Fig. 3. Electronic absorption spectra of 3 in different pH: (a) ethanol, (b) pH 1.4, (c) pH 3.2, (d) pH 5.1, (e) pH 7.4, (f) pH 9.7, (g) pH 12.5, and (h) pH 13.2.
Fig. 4. Fluorescence spectra of solutions of compound 3 at kex = 254 nm in different solvents: (a) ethanol, (b) dimethyl sulfoxide, and (c) 1,4-dioxane.
Fig. 5. Fluorescence spectra of solutions of compound 4 at kex = 269 nm in different solvents: (a) ethanol, (b) dimethyl sulfoxide, (c) dimethylformamide,
(d) chloroform, and (e) 1,4-dioxane.
high yielding procedure that could be applied for the
synthesis of similar derivatives with other nucleic bases
and heterocycles as well. These molecules are attractive
precursors for the synthesis of neutral carbocyclic nucle-
oside and polynucleotide analogs. The absorption and
fluorescence spectra of these compounds show significant
dependence on specific and non-specific solute–solvent
interactions.

20
H.H. Hammud et al. / Journal of Molecular Structure 881 (2008) 11–20
Fig. 6. Fluorescence spectra of solutions of compound 6 at kex = 269 nm in different solvents: (a) ethanol, (b) dimethyl sulfoxide, (c) chloroform, (d) 1,4-
dioxane, and (e) diethyl ether.
[23] Z. Abdullah, N. Mohd, M. Abas, B. Low, Malaysian J. Anal. Sci. 4
Acknowledgements
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