Hydrogen-bond effect, spectroscopic and molecular structure investigation of sulfamethazine Schiff-base: Experimental and quantum chemical calculations

Article abstract of DOI:10.1016/j.molstruc.2013.02.028

Comprehensive theoretical and experimental structural studies on N-(4,6-dimethyl-pyrimidin-2-yl)-4-[(2-hydroxy-benzylidene)-amino] benzenesulfonamide (SMS) have been carried out by elemental analysis, FT IR, ¹H NMR, UV-Vis. and MS. Optimized mo

Full text of DOI:10.1016/j.molstruc.2013.02.028

Accepted Manuscript
Hydrogen-bond effect, spectroscopic and molecular structure investigation of
sulfamethazine Schiff-base: Experimental and quantum chemical calculations
Ahmed M. Mansour, Nour T. Abdel Ghani
PII:
S0022-2860(13)00173-7
DOI:
http://dx.doi.org/10.1016/j.molstruc.2013.02.028
MOLSTR 19577
Reference:
To appear in:
Journal of Molecular Structure
Received Date:
Revised Date:
Accepted Date:
12 January 2013
23 February 2013
25 February 2013
Please cite this article as: A.M. Mansour, N.T. Abdel Ghani, Hydrogen-bond effect, spectroscopic and molecular
structure investigation of sulfamethazine Schiff-base: Experimental and quantum chemical calculations, Journal of
Molecular Structure (2013), doi: http://dx.doi.org/10.1016/j.molstruc.2013.02.028
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Hydrogen-bond effect, spectroscopic and molecular structure investigation of
sulfamethazine Schiff-base: Experimental and quantum chemical calculations
*
Ahmed M. Mansour , Nour T. Abdel Ghani
Chemistry Department, Faculty of Science, Cairo University, Gamaa Street, Giza 12613, Egypt
Abstract
Comprehensive theoretical and experimental structural studies on N-(4,6-Dimethyl-pyrimidin-2-
yl)-4-[(2-hydroxy-benzylidene)-amino]benzenesulfonamide (SMS) have been carried out by elemental
1
analysis, FT IR, H NMR, UV-Vis. and MS. Optimized molecular structure and harmonic vibrational
frequencies have been investigated by DFT/B3LYP and HF methods combined with 6-31G(d) basis
set. Stability of the molecule arises from hyperconjugative interactions, charge delocalization and
intramolecular hydrogen bond has been analyzed using natural bond orbital (NBO) analysis. Electronic
structures were discussed by TD-DFT method and the descriptions of frontier molecular orbitals and
1
the relocation of the electron density were determined. H NMR chemical shifts were computed by
Gauge-invariant atomic orbital (GIAO) method in both gas and DMSO media, using the polarizable
continuum model (PCM). Structure-activity relationship has been used to correlate biological activity
with some appropriate quantum descriptors such as EHOMO, ELUMO, energy gap, dipole moment (μ),
global hardness (η), softness (S), electrophilicity index (ω), molecular polarizability (α), Mulliken
electronegativity (χ), Mulliken charge (Qi) and molecular electrostatic potential (MEP).
Key Words: Sulfamethazine; TD-DFT; hydrogen bond; NBO; MEP; SAR
*
Corresponding author, Tel.: +2 02 01222211253; Fax: +20 2 35728843. E-mail: inorganic_am@ yahoo.com
1
. Introduction
Sulfonamides constitute an important class of antimicrobial agents in the world owing to their
low cost, low toxicity and excellent activity against bacterial diseases. Sulfonamides act as competitive
inhibitors of the enzyme dihydropteroate synthase in bacteria and catalyze the conversion of p-amino-
benzoic acid into an essential nutrient for some bacteria [1]. Sulfonamides are bacteriostatic rather than
bactericidal due to their ability to slow down or prevent bacterial multiplication in wounds or infected
systems without appreciable toxicity to the body tissues [2]. Recently, sulfonamides have been replaced
by antibiotics, since antibiotics have greater potency and several strains of bacteria have acquired
resistance to sulfonamides. Moreover, sulfonamides were found to have no clinical usage on
Mycobacterium tuberculosis [3]; their role is controversial, and thus they are not recommended for a
routine susceptibility testing of M. tuberculosis isolates [4].
1

Due to the well-known problems of sulfonamide therapy [5], especially those related to growing
bacterial resistance adverse effects and low bioavailability, sulfonamides have been modified either
through formation of Schiff-base [6] and/or metal complexes [7] to initiate new derivatives with more
convenient antimicrobial properties. Sulfamethazine (4-amino-N-(4,6-dimethyl-2-pyrimidinyl)benzene-
sulfonamide) is a sulfa drug that is clinically used in veterinary medicine as an antibacterial agent to
treat livestock diseases such as gastrointestinal and respiratory tract infections. Several sulfamethazine
Schiff-base [6] were found to be able to stop the growth of some bacterial species e.g. Pseudomonas
aeruginosa, Escherichia coli, Pseudomonas aeruginosa, Shigella flexneri, Klebsiella pneumoniae and
Salmonella typhi.
The absence of any quantum-chemical calculations [8-10] on sulfa-drug salicyaldehyde Schiff-
base in the literature, to the best of our knowledge, and seeking to understanding the antibacterial
behavior of sulfamethazine upon modification encouraged us to discover the structural features of SMS
(
(
Fig. 1). Comprehensive experimental and theoretical studies of SMS at density functional theory
DFT) and ab inito Hartree Fock (HF) have been carried out aiming to obtain complete reliable and
precise structural features of the investigated compound. Atomic charges, distribution of electron
2
density (ED) in various bonding and anti-bonding orbitals and stabilization energies, E have been
calculated by NBO analysis. Investigations have been done to identify HOMO-LUMO energy gap,
non-linear optical (NLO) effects, harmonic vibrational modes, electronic structure, and chemical shift.
Correlation between biological activity and some appropriate quantum descriptors [11] such as EHOMO
LUMO, energy gap, dipole moment (μ), global hardness (η), softness (S), electrophilicity index (ω),
molecular polarizability (α), Mulliken electronegativity (χ), molecular electrostatic potential (MEP) and
Mulliken charge (Q ) have been also carried out.
. Experimental
,
E
i
2
2.1. Synthesis and characterization
An aqueous solution (15 mL) of sodium sulfamethazine (3.01 g, 0.01 moles) was mixed with an
ethanolic solution of salicyaldehyde (1.22 g, 0.01 moles/35 mL) and the mixture was then refluxed for
h, where the color of the solution is gradually changed from colorless to orange. After that, the
reaction mixture was acidified with dilute H SO where a solid of sulfamethazine Schiff-base was
4
2
4
separated and re-crystallized from ethanol. The elemental analyses data are in a good agreement with
those calculated for the suggested formula as follows: Anal. Calcd. %C, 59.67; %H, 4.70; %N, 14.65.
Found: %C, 59.54; %H, 5.03; %N, 14.57. The mass spectrum of the titled compound shows a
molecular ion peak at m/z 382 with a fragmentation pattern as shown in scheme (1).
2

2.2. Physical measurements
FT IR spectrum was recorded as potassium bromide pellet using FT IR-460 plus, JASCO. EIMS
1
was obtained from SHIMADZU QP-2010 plus mass spectrometer at 70 eV. H NMR spectrum was
6
recorded at 300 MHz in DMSO-d using Varian-Oxford Mercury VX-300 NMR. Electronic absorption
spectra were obtained by UV-Vis. SHIMADZU Lambda 4B automated spectrophotometer. Elemental
microanalyses were performed at Micro-analytical Center, Cairo University.
2.3. Computational details
Full-unconstrained geometry optimization of SMS has been performed at HF and DFT (B3LYP)
methods combined with 6-31G(d) basis set using Gaussian 03 package [12]. The optimized geometries
were verified by performing a frequency calculation at the same level of theory. Vibrational modes
were analyzed via Gaussview software [13]. At this level of theory, the calculated harmonic wave-
numbers were found to be higher than the corresponding experimental quantities due to the fact of the
electron correlation approximate treatment, anharmonicity effects and basis set deficiencies [14-15].
Vibrational frequencies are scaled as 0.958 for B3LYP/6-31G(d) for the range of wavenumbers above
−1
−1
1
700 cm and 0.983 for those below 1700 cm [16], as well as 0.9067 for HF/6-31G(d) to account
these systematic errors. The NMR chemical shifts were computed at B3LYP/6-311+G(2d,p) and HF/6-
1
3
1G(d) level of theory in the gaseous state by applying GIAO approach [17] and the values for the H
isotropic were referenced to TMS, which was calculated at the same level of theory. The effect of
solvent (DMSO) on the theoretical NMR parameters was performed using the default PCM model.
According to Koopman’s theorem [18], the ionization energy (I) and electron affinity (A) can be
obtained as, I = -EHOMO and A = -ELUMO. Mulliken electronegativity (χ) can be calculated as follows: χ
=
(I + A)/2. Softness (S) is a property of molecule that measures the extent of chemical reactivity. It is
defined as the reciprocal of hardness (η) and η = (I - A)/2 [19]. The electrophilicity index (ω), ω =
2
(
-χ /2η) [20] is a measure of energy lowering due to maximal electron flow between donor and
acceptor. NBO calculations [21] were performed using NBO 3.1 program as implemented in Gaussian
03 package at DFT/B3LYP level.
2
.4.Antimicrobial activity
The antimicrobial activities of the tested samples were carried out as previously described [8]
using culture of Staphylococcus aureus, as a Gram-positive bacterium and Escherichia coli, as a Gram-
negative bacterium according to a modified Kirby-Bauer disc diffusion method [22] under standard
conditions using Mueller-Hinton agar medium (tested for composition and pH). The antimicrobial
3

activities could be calculated as a mean of three replicates. The results (in DMSO) were compared with
a similar run of Tetracycline as an antibacterial agent.
3. Results and discussion
3
.1. Geometry optimization
Full geometry optimization of SMS was performed at DFT/B3LYP/6-31G(d) and HF/6-31G(d)
level of theory. The optimized structure was checked as minima on the potential energy surfaces by
frequency calculations. A view of the optimized structure and its atoms numbering are shown in Fig. 1.
Selected bond distances, angles and charges are listed in Table (1). The optimized geometry is
compared with the crystallographic data of sulfamethazine [23] and those closely related molecules, 2-
[(5-Chloro-2-hydroxy-benzylidene)-amino]-N-(4,6-dimethyl-pyrimidin-2-yl)benzenesul-fonamide (4-
Cl-SMS) [24] and 2-[(5-Bromo-2-hydroxy-benzylidene)-amino]-N-(4,6-dimethyl-pyrimi-din-2-yl)ben-
zenesulfonamide (4-Br-SMS) [25]. The global energy minimum of SMS is -1577.688 Hartree (-
5
5
9
.90×10 kcal/mol) and -1569.829 Hartree (-9.85×10 kcal/mol) as calculated by DFT/B3LYP and HF,
respectively. The optimization studies showed that the molecule belongs to C1 symmetry point group.
It is well known that bond lengths and angles given at DFT/B3LYP level of theory are usually more
accurate than HF owing to the inclusion of electron correlation [26]. On the contrary, in the present
study, it was found that HF method correlates well for the molecular parameters comparing with
DFT/B3LYP method (Table 1). Better agreement between the calculated bond lengths of SMS and the
experimental data of sulfamethazine is found, since the largest difference is found to be 0.028 Å and
0
.076 Å as calculated at HF and DFT/B3LYP, respectively. In addition, the bond angles of the titled
compound are slightly deviated from those of sulfamethazine by 0.2-2.6° for HF and 0.3-3.7° for DFT,
where the larger inconsistency is observed to C3S12N13. For the comparison with 4-Cl derivative, the
largest difference between the experimental of 4-Cl and calculated bond lengths is 0.027 Å for HF and
0
.079 Å for DFT/B3LYP. Moreover, the standard deviation (SD) in the bond lengths is found to be
.011 Å for HF and 0.023 Å for DFT/B3LYP method. A linear fit between the experimental and
0
theoretical bond distances confirms that HF/6-31G(d) method gives better agreement than DFT/
B3LYP/6-31G(d) and SMS bond lengths are more close to 4-Cl-SMS derivative than 4-Br-SMS as
follows:
2
d
calcd = 1.0429dexp-0.0582
calcd = 1.0403dexp-0.0534
calcd = 1.0796dexp-0.1159
R = 0.9876 SD = 0.011 HF, 4-Cl-SMS
2
d
R = 0.9846 SD = 0.013 HF, 4-Br-SMS
2
d
R = 0.9900 SD = 0.011 HF, sulfamethazine
4

2
d
calcd = 1.0723dexp-0.0846
calcd = 1.0688dexp-0.0785
calcd = 1.1243dexp-0.1622
R = 0.9785 SD = 0.023 DFT/B3LYP, 4-Cl-SMS
2
d
R = 0.9876 SD = 0.025 DFT/B3LYP, 4-Br-SMS
2
d
R = 0.9836 SD = 0.020 DFT/B3LYP, sulfamethazine
To account the effect of intramolecular H-bond between phenolic OH and azomethine group,
O43H44…N11, on the optimized structure of SMS and its structural features, we optimized SMS in
presence (F
presence of hydrogen bond increases the stability of SMS by 11.296 kcalmol . The comparison
between F and FII reveals that O43H44 and N11C32 bond distances are lengthened by 0.028 and 0.011
I
) and absence (FII) of intramolecular H-bond at DFT/B3LYP/6-31G(d). It was found that
-
1
I
Å, respectively, while the C36O43 bond length is shortened by 0.024 Å upon the formation of H-bond.
The shortening of C36O43 bond distance is coming from the redistribution of partial charges on O43
atom as the unpaired electron is significantly delocalized with an increase of the double bond character
of C-O bond. On the other hand, the C-C bond lengths of salicyaldehyde moiety are not affected by
presence of hydrogen bond except C34C36 bond, which is lengthened by 0.010 Å. In addition, the
salicyaldehyde moiety appears little distorted and their angles are slightly out of the perfect hexagonal
structure whether the H-bond is present or not. The breakdown of hexagonal symmetry is obvious from
the elongation of C34-C36 (1.403 Å) and shortening of C35C37 (1.374 Å), as calculated by HF method
(Table 1). The C16N21 and C16N22 bond distances in the pyrimidine moiety are found to be shorter
than the corresponding observed values of 4-Br derivative [25]. The inconsistency between the latter
bonds may be justified on the basis that the calculations were performed on a single molecule in the
gaseous state contrary to the experimental values, which were recorded in presence of intermolecular
interactions.
3
.2. Natural bond orbital (NBO) analysis
NBO approach of Weinhold and co-workers [21] has been frequently used in evaluation of intra-
and intermolecular interactions and provides a convenient basis for investigating charge transfer or
conjugative interaction in molecular systems. NBO analysis was performed to provide the contribution
of atomic orbitals to NBO σ and π hybrid orbitals for bonded atom pairs. Three NBO hybrid orbitals
are defined, bonding orbital (BO), lone pair (LP) and core (CR). The ideal Lewis structure picture is
constructed from Lewis σ-type (donor) NBOs that are complemented by non-Lewis σ-type (acceptor)
NBOs. The filled NBOs describe covalency effects in molecules, while the anti-bonds represent empty
valence-shell capacity and spanning portions of the atomic valence space that are formally unsaturated
by covalent electrons. Weak occupancies of the valence anti-bonds signal irreducible departure from an
5

idealized localized Lewis picture, i.e. true "delocalization effects". Hyperconjugation is given as a
stabilizing effect that arises from an overlap between an occupied and another electron deficient orbital.
The hyperconjugative interaction energy was deduced from the second-order perturbation approach of
Fock Matrix in NBO basis between donor-acceptor orbitals [27]. The larger the second order
2
interaction energy (E ) value, the more intensive is the interaction between electron donors and electron
acceptors, i.e. the more donating tendency from electron donors to electron acceptors and the greater
the extent of conjugation of the whole system. These interactions can be identified by finding an
increase in the electron density (ED) of the anti-bonding orbital that weakens the respective bonds.
*
NBO analysis shows that π(C1-C2) and π(C3-C4) participate as donors and π (C5-C6) as
-
1
acceptor with charge transfer energy values ∼ 22 and 16 kcalmol , respectively. These interactions
1
.90
weaken C5-C6 bond with elongation of its bond length, 1.406 Å. The σ(C5-C6) is formed from sp
1
.76
hybrid on C5 (65.55% p) and sp on C6 (63.69% p). Other π electrons hyperconjugative interactions
are found in the aniline residue (No. C1 to C6) revealing the delocalization of π electrons as
summarized in Table S1 (supplementary materials). It was found that S12-O14 bond (σ(S12-O14) =
2
.66 0.06
3.01 0.02
0
.582 sp
d
+ 0.813 sp
d
) is slightly shorter than S12-O15 bond (σ(S12-O15) = 0.581
2
.58 0.06
2.96 0.02
sp
d
+ 0.813 sp
d
). The slightly increasing in p character of one S=O relative to the other
group. The lone pair interaction of LP(1)N13
leads to an inequality in the bond distances of SO
2
16.18
2
-1
(
sp
) with anti-bonding π*(C16-N22) (ED ≈ 0.430e and E = 35 kcalmol ) has a small energy
difference (∼0.30 a.u.) supporting the electron delocalization between sulfonamidic nitrogen (N13)
and pyrimidine ring with improvement of the coordinating ability of pyrimidine nitrogen (N21). The
*
*
LP(1)N21→π (C16-N22) and LP(1)N22→π (C16-N21) charge transfers inside the pyrimidine ring
lead to stabilization of pyrimidine moiety.
NBO analysis has been performed to throw more light on intramolecular H-bond, intra charge
transfer (ICT), hybridization, delocalization of electron density and cooperative effect due to LP(N11)
6

*
*
→
σ (O43-H44). The intra H-bond is formed by an orbital overlap between LP(N11) and σ (O43-H44)
with a charge transfer causing stabilization of H-bond system. Hence, H-bonding interaction leads to an
*
increase in electron density (ED) of σ (O43-H44) and lengthening of O-H bond, 0.028 Å as previously
mentioned. Therefore, the nature and strength of H-bond can be explored by studying the redistribution
I
of electron densities in the vicinity of O-H bond. Comparison between intra hydrogen (F ) and non H-
bonded (FII) systems manifests some evidences about the formation of strong intramolecular interaction
*
between N11 lone electron pair and σ (O43-H44) orbital. The lone pair interaction LP(1)N11→
*
2
-1
RY (H44) (ED ≈ 0.0044e and E = 0.58 kcalmol ) is a fact for intra charge transfer (ICT). The
occupation number of LP(1)N11 (Table 2) decreases by 0.028e through H-bond formation and this is
clearly reflected in geometry as C36-O43 contracts to an amount of 0.024 Å with respect to non H-
2
.86 0.01
bond isomer. In addition, the p characters of C36-O43 bond, σ(C36-O43) = 0.581 sp
d
+ 0.814
1.82
3.05 0.01
1.90
sp , increase to 0.574 sp
d
+ 0.574 sp
which substantiate the double bond character in F
I
1
.78
2.11
system. Similar, the p characters of C32-C34 bond is increased from sp
(C32) and sp
(C34) to
1.81
2.13
*
sp (C32) and sp (C34) with gaining of 0.016e. In addition, the electron density of π (C34-C36) is
increased significantly by 0.021e upon H-bond interaction, which in turn leads to weaken of C34-C36
2
bond, its elongation and concomitant red shift of its stretching frequency. This is an evident from the E
-
1
energy (38.75 kcalmol ) of the hyperconjugative intramolecular interaction in F
I
system, LP(2)O43→
*
-1
π (C34-C36) (Table S1, supplementary materials) comparing with 29.65 kcalmol for non H-bonded
system, FII
.
3
.3. Mulliken atomic charges
The calculation of effective atomic charge plays an important role in the application of quantum
mechanical calculations to the molecular systems. The total (σ + π) charge distribution in molecular or
ionic species is a very important parameter on the basis of which several important properties may be
discussed. These include hydrogen bond proton acceptor ability and character (dipolar vs. zwitterionic)
of the studied species. As shown in Fig. 2, the C6 atom is the only carbon atom in the aniline residue
(
(
C1 to C6) of SMS has a positive value, 0.294e that is attributed to the σ withdrawing character of N11
-0.527e). Similar, the C16 atom possesses the maximum positive charge (0.658e) among all carbon
atoms in the reported compound that is mainly due to the attachment of three electronegative atoms,
N13, N21, and N22, which withdraw electrons from C16. Moreover, both C17 (0.338e) and C18
(
0.336e) atoms have positive charges with respect to C19 (-0.233e) as a result of the attachment of
negatively charges methyl groups (C23 and C24). All the hydrogen atoms have positive charges within
the range from 0.134e to 0.427e as calculated by DFT/B3LYP. The ionizable proton (H31) has a
7

greater positive atomic charge (0.374e) that reduces to some extent the greater negative atomic charge
on N13 atom. In addition, it was found that N13 has the highest negative charge in the titled compound
by reserved electrons from sulfur atom. The highest positive value on hydrogen atoms is located upon
H44 (0.427e). The presence of large negative charge on N11 (-0.527e) and O43 (-0.645e) atoms and
net positive charge on H44 (0.427) atom may suggest the formation of intramolecular interaction. This
is confirmed by presence of positive charge on C32 (0.102e), C34 (0.081e), and C36 (0.314e)
comparing with other carbon atoms in the same moiety. The O14 (-0.546e) possesses a more negative
charge than the other sulfonyl O, O15 (-0.514e). This seems to indicate presence of some sort of
interaction with N13H31 with D…A distance of 2.45 Å.
3
.4. Non-linear effects
Nonlinear optical (NLO) effects arise from the interactions of electromagnetic fields in various
media to produce new fields altered in phase, frequency, amplitude or other propagation characteristics
from the incident fields [28]. NLO provides the key functions of frequency shifting, optical
modulation, switching and memory for the emerging technologies in areas of telecommunications,
signal processing and optical interconnections [26]. Dipole moment, the first derivative of energy with
respect to an applied electric field, is a measure of the asymmetry in the molecular charge distribution
and is given as a vector in three dimensions. Dipole moment is strictly determined for neutral
molecules. For charged systems, its value depends on the choice of origin and molecular orientation.
The non-linear optical response of an isolated molecule in an electric field E (ω) can be presented as a
i
Taylor series expansion of the total dipole moment, μtot, induced by the field:
where α is the linear polarizability, μ is the permanent dipole moment and B are the first
ij
o
ijk
hyperpolarizability tensor components. Another way of obtaining information about the distribution of
electrons is given by computing the polarizability. This property depends on the second derivative of
the energy with respect to an electric field. The average linear polarizability (αtot) and the anisotropy of
the polarizability (Δα) are calculated as follows [29]:
8

Higher order polarizabilities (hyperpolarizabilities β, γ, etc.), which describe the non-linear
response of atoms and molecules are related to a wide range of phenomena from non-linear optics to
intermolecular forces, such as the stability of chemical bonds, as well as the conformation of molecules
and molecular aggregates [28-29].The second order polarizability or first hyperpolarizability (βtot) is
calculated as follows:
The polarizabilities and hyperpolarizability are reported in atomic units (a.u.), the calculated values
−24
have been converted into electrostatic units (esu) (α: 1 a.u. = 0.1482 × 10 esu, β: 1 a.u. = 8.6393 ×
−33
1
0
I
esu). The hyperpolarizability, dipole moment and polarizability for intra H-bonded system (F ) at
DFT/B3LYP and HF level of theory and non H-bonded system (FII) at DFT/B3LYP are presented in
Table 3. Herein, the dipole moment and the mean polarizability are found to be 5.64 Debye and 238.83
a.u., respectively, as calculated by HF method. The highest value of dipole moment is observed for
-30
y
component μ , 5.30 Debye. The first hyperpolarizability (βtot) value is found to be 6.38 × 10 esu.
Urea is a prototypical molecule (1.52 Debye) used for studying the NLO properties [26] of the
molecular systems and it has been used frequently as a threshold value for comparative purposes. It can
-33
be seen that the calculated βtot is nearly 32 times higher than urea (343.27×10 esu at HF/6-31G(d))
revealing that the titled compound can act as a good NLO material.
3
.5. Electronic structure
Sulfonamides exhibited a single absorption band at 260 nm [30]. The electronic spectrum of SMS
in ethanol (Fig. 3) displayed two absorption bands at 214 and 275 nm as well as a shoulder at 341 nm.
The absorption spectrum of the titled Schiff-base was observed in solvents of different polarity and of
hydrogen bond formation tendency like ethanol, dioxane, cyclohexane, chloroform and DMSO.
Generally, n-π* transitions are blue shifted with increasing solvent polarity. This arises from increased
solvation of the lone pair, which lowers the energy of the n orbital. As shown in Fig. 3, the solvent in
which the absorbing species is dissolved has no effect on the spectrum that is in agreement with our
theoretical spectra (Fig. 4) as calculated at TD-DFT level of theory. Thus, the n-π* transition is not
observed in SMS, although the system has many lone pairs. The values of the observed transition
P
energies (Eobs), oscillator strengths (fobs) and ionization potential (I ) of all the bands in the electronic
spectra of the titled compound in different solvents were calculated [31] and tabulated in table 4.
9

The nature of the electronic transitions observed in the UV-Vis. spectra of the titled compound in
different solvents has been also studied by TD-DFT method. The lowest 30 spin-allowed excitation
states were taken into consideration for calculation of its electronic absorption spectra. The absorption
spectra were simulated using GAUSSSUM [32]. Each excited state was interpolated by a Gaussian
-1
convolution with the full-width at half-maximum (FWHM) of 3000 cm . The calculated energies of
excitation states with transition strength (f > 0.05) are tabulated (Table S2, Supplementary
material).The primary feature of TD-DFT calculated absorption bands of SMS in gaseous state (Fig. 4)
shows mainly four absorption bands at 226, 273, 312 and 348 nm with oscillator strength 0.051, 0.247,
0
.282 and 0.373, respectively. The lowest absorption band at 348 nm predominately arises from
transition of HOMO to LUMO (96%), while the excitation energy at 312 nm (3.97 eV) is contributed
mainly from HOMO-1 to LUMO with configuration interaction coefficient up to 0.85. The sharp band
at 273 nm is assigned to a combination of HOMO-4→LUMO (37%) and HOMO-5→LUMO (20%).
The highest energy transition at 226 nm characterizes mainly the transitions HOMO-1→LUMO+2
(36%)/LUMO+3 (14%) and HOMO→LUMO+4 (16%). On the other hand, the theoretical UV-Vis.
spectra of SMS in the different solvents are typical and unique from that of gaseous state with four
bands at 230, 291, 328 and 385 nm and a shoulder at 248 nm. The lowest energy electronic transition
(
HOMO→LUMO) (Fig. 5) is red shifted to 385 nm (3.22 eV), while HOMO-1→LUMO is allocated at
28 nm (3.77 eV) comparing with the corresponding values in the gaseous state. Moreover, the
3
excitation energy at 291 nm is attributed to HOMO-3→LUMO (43%) and HOMO-4→LUMO (28%)
transitions. The shoulder at 248 nm is resulting from HOMO→LUMO+3 (70%), while the highest
energy transition at 230 nm is assigned to HOMO-1→LUMO+2 (52%) and HOMO→LUMO+5 (26%).
3.6. Vibrational assignment
The calculation of the vibrational frequencies is very useful task for the assignment of the spectra.
The vibrational frequencies obtained by quantum chemical calculations are typically higher than the
corresponding experimental quantities owing to several factors such as anharmonicity and basis set
deficiencies [14-15]. Experimentally, the asymmetric and symmetric SO
2
stretching vibrations are
-
1
-1
observed at 1346 and 1150 cm in SMS comparing with those of sulfamethazine, 1331, and 1157 cm
33]. The calculated νass(SO ) and νss(SO
[
2
2
) modes with HF/6-31G(d) method (No. 44 & 65) give better
agreement with the observed values (Table S3, Supplementary material), while DFT/B3LYP/6-31G(d)
estimates lower than the typical values given in the experimental study [34]. Thus, HF calculations
approximate the observed frequencies much better than the B3LYP/6-31G(d) results for S=O stretching
-
1
-1
vibrations. The scaled band at 593 cm is assigned to O=S=O bending mode. The band at 856 cm is
1
0

-
1
due to ν(C-S) (Fig. 6), whereas the band at 3377 cm is assigned to ν(NH) that is deviated from the
-
1
theoretical value, 3430 and 3480 cm , as calculated by DFT/B3LYP and HF, respectively. This
discrepancy may be justified on the basis that the calculations were performed on a single molecule in
the gaseous state contrary to the experimental values, which were recorded in presence of inter-
molecular interactions, between NH and phenolic O atom, as experimentally confirmed by the packing
diagram of 4-Cl-SMS [24]. The ν(C=N) mode of azomethine group is overlapped with the ν(C=C)
-
1
vibrations due to the effect of intramolecular H-bond, whereas the scaled value is found at 1706 cm
-
1
for HF and 1680 cm for DFT (B3LYP). The characteristic bands observed in the spectra of alcohols
and phenols are resulted from O-H and C-O bond stretching [35]. These vibration modes are sensitive
to hydrogen bonding. The non-hydrogen-bonded or "free" hydroxyl group of alcohols and phenols
-
1
absorbs strongly in the 3650-3584 cm , while the hydrogen bonded one appears in the region 3550-
-
1
3
200 cm . In the present work, SMS has a strong hydrogen bond in the solid state, which makes the IR
-
1
spectrum shows strong and broad absorption band in the 3500-2200 cm region. Thus, the assignment
-
1
of the O-H stretching vibration may be difficult. However, the theoretically scaled value at 3529 cm is
assigned to ν(OH) as calculated at the HF level of theory. In addition, the assignment of the stretching
mode of C-O is not easy due to intramolecular hydrogen bond formation and consequently increasing
-
1
of the double bond character [9]. However, the scaled value at 1308 cm is assigned to ν(C-O). SMS
molecule possesses two CH groups attached to the pyrimidine ring. For assignments of CH group
frequencies theoretically, nine fundamentals can be associated to each CH group [9]. The bands
(C23) asymmetric mode, while those at 3014 and
) of methyl group no. 24. Moreover, the bands at 2930 and 2931
) mode for C23 and C24 methyl groups, respectively. Infrared bands
3
3
3
-
1
observed at 3013 and 2988 cm are ascribed to CH
3
-
1
2
989 cm are attributed to νass(CH
3
-
1
cm are allocated to the νss(CH
3
-
1
opb
ipb
sb
established at 1488, 1478, 1409, 1059, 1030 and 268 cm are attributed to CH
, CH
, CH ,
3
3
3
opr
ipr
CH3 , CH3 and τCH (C23) vibration mode, respectively, at DFT/B3LYP level of theory. These
3
−
1
vibrations are established at 1488, 1478, 1412, 1059, 1030 and 247 cm , for methyl group no. 24,
respectively.
1
3
.7. H NMR spectral analysis
1
In order to provide an unambiguous assignment of H NMR spectrum of the studied compound,
we undertook a series of NMR calculations at DFT/B3LYP/6-311+G(2d,p) and HF/6-31G(d) level of
1
theory by applying GIAO approach [17]. The values for the H isotropic were referenced to TMS,
which was calculated at the same level of theory. The default PCM model provided by Gaussain 03
was also tested in order to describe the influence exerted by solvent (DMSO) on the NMR spectrum of
1
1

1
the given compound. As shown in Table 5, the H chemical shifts of methyl protons (H25-30), aromatic
proton of pyrimidine moiety (H20) and azomethine proton (H33) are in a good agreement with the
theoretically computed values, while the chemical shifts of aromatic protons are experimentally
difficult to assign. The calculated chemical shifts for aromatic protons are found to be at 7.66 (H
7
), 8.56
(
H ), 9.12 (H ), 7.66 (H10), 7.22 (H40), 7.22 (H41), 8.20 (H42) and 8.20 (H45) as calculated by HF/
8 9
6
-31G(d) method in DMSO as a solvent. The titled molecule shows a broad singlet signal in DMSO at
2.50 ppm that is assigned to phenolic proton (H44) that disappears by deuteration. The high
1
deshielding value of phenolic proton is attributed to intramolecular H-bond formation with azomethine
group. Moreover, the theoretical chemical shift for the intramolecular H-bonding proton, calculated by
HF/6-31G(d), shows better agreement with the experimental value than that calculated by DFT/
B3LYP/6-311+G(2d,p) in DMSO. The sulfonamide proton (H31) appears at 11.10 ppm and is shifted
towards higher magnetic field than the calculated one by DFT/B3LYP/6-311+G(2d,p) [10]. Although,
the chemical shift of sulfonamide proton in DMSO shows little improvement in relation to the gaseous
state, but this value remains unacceptable apart from the experimental value, which can reflect that the
chemical shift associated with this proton is not correctly described by continuum model. Thus, it is
clear that PCM model fails in reproducing the experimental findings for the hydrogen-bonded protons
and specific solute-solvent interactions are expected to completely explain the NMR spectra of the
studied compound [17]. Finally, it is worthy to mention that the H atom is the smallest of all atoms and
mostly localized on the periphery of molecules and thus its chemical shifts would be more susceptible
to intermolecular interactions in the aqueous solution comparing with those for other heavier atoms.
Another important aspect is that, hydrogen attached or nearby electron-withdrawing atom or group can
decrease the shielding and moves the resonance of attached proton towards to a higher frequency. By
contrast, electron donating atom or group increases the shielding and moves the resonance towards to a
lower chemical shifts.
3
.8. Antimicrobial activity and structure-activity relationship (SAR)
The antimicrobial activities of the titled compound were studied using culture of Staphylococcus
aureus as a Gram-positive bacterium and Escherichia coli as a Gram-negative bacterium and the results
were compared with respect to those of sodium sulfamethazine and Tetracycline as a standard. It was
found that sodium sulfamethazine has a capacity of inhibiting the metabolic growth of the investigated
bacteria to different extents and it is slightly more efficient than tetracycline, while SMS was found to
inactive against E. coli at concentration of 20 mg/mL. In addition, SMS is found to be toxic against the
studied Gram-positive bacterium, S. aureus, but with incomplete inhibition at this concentration. The
1
2

variation in the antimicrobial activity of SMS against different organisms depends either on the
impermeability of the cells of the microbes or on differences in ribosome of microbial cells. To
understand, to certain extent, the microbiological behavior of SMS and sodium sulfamethazine, it is
worthy to clarify that the truly active antimicrobial species of the sulfonamide drugs is the ionic form
i.e. sulfonamides penetrate bacterial cells in the unionized form and once they are inside a cell, their
bacterial action would be due to its ionized form [11]. For SSM, this compound would penetrate into
the cell and the release of the anionic form of sulfonamide would be achievable, not as the ionic
a
sodium sulfamethazine, but according to the value of the ionization constant, pK of sulfonamide
group. In addition, the variation of toxicity between SMS and sodium sulfamethazine may come from
the ability or inability to cross membranes and hence there is a high correlation with the lipophilicity.
The ultimate goal of structure-activity relationship (SAR) studies is to correlate the biological
activity of a series of compounds with some appropriate descriptors. Among different descriptors, the
electronic properties of molecules and the quantum chemical descriptors based on DFT have been
found useful in several SAR studies [11]. From the results of DFT calculations, different descriptors
such as EHOMO, ELUMO, energy gap, dipole moment (μ), global hardness (η), softness (S),
electrophilicity index (ω), molecular polarizability (α), Mulliken electronegativity (χ) and Mulliken
i
charge (Q ) were selected for SAR analysis. The computed quantum chemical descriptors based upon
DFT calculations are presented in Table 6. The energies of frontier molecular orbitals [36] are
important parameters in several chemical and pharmacological processes. EHOMO measures the electron
donating character of a compound, while ELUMO measures its electron accepting character. Thus, the
greater the EHOMO is, the greater the electron donating capability will be, and the smaller the ELUMO is,
the lower the resistance to accept electrons will be. Fig. 5 shows HOMOs and LUMOs molecular
orbitals with their energies for the titled compound. For the inactive compound studied in this work,
ELUMO is high (-6.08 eV), whereas the active sodium sulfamethazine has a small value, 0.98 eV. Hence,
sodium sulfamethazine is less efficient electron acceptor compound than the studied compound. As
shown in Table 6, the decrease in Mulliken charge on N13 atom of sodium sulfamethazine is associated
with an increase in biological activity. Thus, active molecule is characterized by a high acidity and a
small charge on N13 atom. The dipole moment (μ in Debye) is another important electronic parameter
that results from non-uniform distribution of charges on the various atoms in a given molecule. Herein,
the high value of dipole moment of SMS decreases markedly the antimicrobial activity [11].
Alternatively, polarizability (α) measures the ability of electrons in a molecule to move easily as a
result of stimulus and here the active sodium sulfamethazine is associated with low polarizability value.
1
3

Molecular electrostatic potential (MEP) is related to the electronic density and is a very useful
descriptor in understanding sites for electrophilic attack and nucleophilic reactions as well as hydrogen
bonding interactions [37].This is correlated with dipole moments, electronegativity, partial charges, and
chemical reactivity of the molecules. These maps allow us to visualize variably charged regions of a
molecule. Knowledge of the charge distributions can be used to determine how molecules interact with
one another. Different values of the electrostatic potential are represented by different colors: red
represents regions of most electro negative electrostatic potential, blue represents regions of most
positive electrostatic potential and green represents regions of zero potential. Potential increases in the
following order: red < orange < yellow < green < blue. Herein, MEP was calculated by the same
method and basis set (B3LYP/6-31G(d)) that used for geometry optimization. As shown in Fig. 7, this
molecule has several sites for electrophilic attack, where the negative regions are mainly located over
the oxygen atoms of sulfonyl group (O15: -0.068 a.u. and O14: -0.06 a.u.). In addition, a negative
electrostatic potential region is observed around the O43 atom of salicyaldehyde residue, -0.040 a.u..
Thus, the calculations suggested that the preferred site for electrophilic attack is oxygen atoms of SO2
then phenolic group. It is interesting to note that the maximum positive regions are localized on
hydrogen atoms of sulfonamidic (H31) and azomethine (H33) and may be center for nucleophilic
activity, with a maximum value of 0.069 a.u., and can be acted as centers for several inter H-bond with
other neighboring molecules.
4
. Conclusion
N-(4,6-Dimethyl-pyrimidin-2-yl)-4-[(2-hydroxy-benzylidene)-amino]benzenesulfonamide
SMS) has been synthesized and characterized extensively by a variety of physico-chemical tools. The
(
effect of intra H-bond on the optimized structure and its structural features is pronounced through NBO
analysis. A linear fit between the experimental and theoretical bond distances confirms that HF gives
better agreement than DFT (B3LYP), and SMS bond lengths are more close to 4-Cl-SMS derivative
than 4-Br-SMS. The presence of large negative charge on N11 (-0.527e) and O43 (-0.645e) atoms and
net positive charge on H44 (0.427) atom may suggest the formation of intramolecular interaction. The
variation of toxicity between SMS and the parent sulfamethazine may come from the ability or inability
to cross membranes and hence there is a high correlation with the lipophilicity. The increase in
Mulliken charge on N13 atom, high dipole moment, polarizability and ELUMO relative to sodium
sulfamethazine is associated with a decrease in biological activity. SMS has several sites for
electrophilic attack such as SO
of SO NH and CH=N groups.
2
and phenolic O, while its nucleophilic sites are localized on H atoms
2
1
4

5
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1
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1
7

Fig. 1: Optimized structure of the titled compound (SMS)
Charge
1
1
0
0
.9
.4
.9
.4
B3LYP/6-31G(d) FI
B3LYP/6-31G(d) FII
HF/6-31G(d) FI
S12
C16
H44
H31
C17 C18
C36
C6
H33
C32
C34
-0.1
-0.6
-1.1
C1 C2 C3
C4
C37
C39
C5
C38
C35
C19
N11
O15
N21
N22 C23 C24
O14
O43
N13
Atom
Fig. 2: Comparison of Mulliken charges for F and F at DFT/B3LYP/6-31G(d), and F at HF/6-31G(d)
I
II
I

1
1
.4
.2
1
SMS-Ethanol
SMS-DMSO
SMS-Dioxane
SMS-Cyclohexane
SMS-Chloroform
0
0
0
0
.8
.6
.4
.2
0
1
90
240
290
340
390
Wavelength (nm)
-5
Fig. 3: Electronic absorption spectra of (3×10 M) of SMS in different solvents.
4
4
3
3
2
2
1
1
5000
0000
5000
0000
5000
0000
5000
0000
Gas
Ethanol
Cyclohexane
DMSO
Chloroform
5
000
0
1
90
240
290
340
390
440
Wavelength (nm)
Fig. 4: Theoretical electronic spectra of SMS in gaseous state, and different solvents

LUMO+5, -4.10 eV
LUMO+3, -4.52 eV
LUMO+4, -4.32 eV
LUMO+1, -5.15 eV
LUMO+2, -4.80 eV
2
30 nm
3
85 nm
2
48 nm
LUMO, -6.08 eV
3
28 nm
HOMO, -8.72 eV
HOMO-1, -8.96 eV
2
91 nm
HOMO-3, -9.86 eV
HOMO-2, -9.36 eV
HOMO-4, -10.02 eV

Fig. 5: Theoretical electronic absorption transitions for SMS in ethanol
(a)
1
8
6
4
2
0
00
0
0
SMS (DFT/B3LYP/6-31G(d))
0
0
3400
2900
2400
1900
Wavenumber (cm )
1400
900
400
-
1
(b)
1
8
6
00
0
0
SMS (HF/6-31G(d))
40
2
0
0
3
400
2900
2400
1900
1400
900
400
-
1
Wavenumber (cm )
(c)
Fig. 6: (a) Experimental and theoretical FTIR spectra of SMS at (a) observed (b) DFT/B3LYP and (c)
HF level of theory

Fig. 7: Molecular electrostatic potential map calculated at DFT/B3LYP level of SMS. The electron
density isosurface is 0.004 a.u.

H C
3
N
O
CH3
OH
N
HN
N
S NH
O
OH
O
NH2
H C
3
N
S NH
O
+
N
O
S NH
O
M = 382
OH
OH
N
N
m/z = 318
H C
3
HN
OH
N
CH3
O
NH2
N
O
N
m/z = 367
H N
S NH
O
2
H N
S NH
O
2
N
O
N
m/z = 195
m/z = 213
m/z = 278
N
S NH
O
H C
3
HN
O
NH2
N
CH3
S NH
O
m/z = 354
O
N
N
O
S NH
O
m/z = 199
N
O
N
S NH
O
S N
O
m/z = 263
H C
3
H C
N
CH3
3
m/z = 339
m/z = 167
N
H N
N
2
O
N
m/z = 123
H C
S NH
O
3
m/z = 248
N
CH3
H3C
N
N
m/z = 108
N
m/z = 94
Scheme (1): Fragmentation pattern of SMS.

Table (1): Selected bond lengths (Å), and angles (º) for intra H-bond (F ) and non H-bond (F ) systems
I
II
Bond length (Å)
Bond angle (˚)
FI
FII
FI
FII
a
b
c
a
b
c
X-ray
SMZ
X-ray
4-Cl
X-ray
4-Br
X-ray
SMZ
X-ray
4-Cl
X-ray
4-Br
DFT/
DFT/
B3LYP
1.388
1.398
1.395
1.391
1.407
1.407
1.785
1.460
1.465
1.709
1.393
1.339
1.334
1.341
1.341
1.396
1.398
1.505
1.505
1.400
1.283
1.461
1.411
1.414
1.384
1.403
1.388
1.401
1.365
0.968
DFT/
DFT/
B3LYP
119.2
121.2
119.1
120.5
119.1
120.5
104.6
108.5
108.4
121.5
101.8
110.4
126.3
119.0
119.6
114.4
117.7
116.0
121.1
117.8
121.2
127.7
115.9
117.8
122.9
120.0
123.0
120.2
120.1
120.5
119.4
121.4
118.3
120.0
121.6
124.2
115.6
HF
HF
B3LYP
1.389
1.398
1.395
1.391
1.406
1.405
1.786
1.460
1.465
1.708
1.394
1.338
1.334
1.341
1.341
1.396
1.398
1.505
1.505
1.404
1.294
1.446
1.410
1.424
1.385
1.404
1.388
1.403
1.341
0.996
1.759
2.650
B3LYP
119.2
121.2
119.1
120.5
119.2
120.5
104.5
108.5
108.4
121.6
101.9
110.5
126.2
119.0
119.6
114.4
117.7
116.0
121.1
117.9
121.2
127.8
115.9
117.7
122.9
121.0
122.6
119.3
120.2
121.1
119.0
121.3
118.8
119.6
121.5
122.2
118.4
C1C2
C2C3
C3C4
C4C5
C5C6
1.377
1.389
1.382
1.384
1.394
1.390
1.762
1.424
1.431
1.656
1.383
1.318
1.312
1.325
1.323
1.384
1.387
1.502
1.502
1.404
1.263
1.462
1.399
1.403
1.374
1.393
1.376
1.393
1.331
0.957
1.903
2.725
1.374 (4)
1.391 (4)
1.383 (3)
1.371 (3)
1.398 (3)
1.400 (4)
1.746 (3)
1.431 (2)
1.435 (1)
1.632 (2)
1.406 (3)
1.333 (3)
1.324 (3)
1.353 (3)
1.347 (3)
1.367 (5)
1.385 (5)
1.497 (5)
1.499 (5)
1.371 (4)
1.378 (4)
1.379 (3)
1.380 (4)
1.384 (4)
1.379 (4)
1.759 (3)
1.422 (2)
1.428(19)
1.629 (3)
1.393 (4)
1.318 (3)
1.332 (3)
1.333 (4)
1.343 (4)
1.378 (5)
1.368 (5)
1.495 (5)
1.503 (4)
1.414
1.374 (6)
1.372 (6)
1.381 (5)
1.375 (6)
1.378 (6)
1.365 (6)
1.753 (4)
1.416 (3)
1.431 (3)
1.629 (4)
1.391 (5)
1.329 (5)
1.330 (5)
1.339 (6)
1.332 (6)
1.368 (6)
1.378 (6)
1.499 (6)
1.506 (7)
1.414 (5)
1.279 (5)
1.448 (6)
1.408 (6)
1.416 (6)
1.362 (6)
1.382 (7)
1.371 (6)
1.380 (7)
1.322 (5)
0.8621
C1C2C3
C2C3C4
C3C4C5
C4C5C6
C5C6C1
119.5
120.8
119.4
120.2
119.6
120.2
105.6
108.5
108.3
120.6
102.1
110.5
127.7
119.3
119.8
114.5
117.9
116.3
121.2
117.1
121.3
127.5
116.3
117.9
122.3
120.2
123.7
119.5
120.2
121.1
118.6
121.7
118.8
118.5
122.6
123.0
117.4
119.8(2)
119.7(2)
120.5(2)
120.6(2)
118.3(2)
120.9(3)
108.2(1)
109.0(1)
108.1(1)
118.9(1)
103.1(1)
109.0(1)
128.0(2)
120.4(2)
120.4(2)
113.8(2)
117.1(2)
115.2(2)
120.4(3)
119.5(3)
121.1(3)
129.1(2)
114.8(2)
119.6 (3)
120.3 (3)
119.7 (2)
120.2 (3)
119.2 (3)
120.9 (3)
106.7
108.9
107.9
118.8 (13)
110.3
103.2
126.2 (2)
118.5 (2)
121.3 (2)
113.8 (2)
117.3 (3)
114.9 (3)
120.5 (3)
119.4 (3)
120.9 (3)
128.9 (3)
115.3 (3)
115.6 (2)
125.2 (2)
124.8 (2)
121.2 (3)
119.6 (3)
120.1 (3)
120.7 (3)
120.4 (3)
120.6 (3)
118.5 (3)
121.1 (3)
120.4 (3)
120.8 (3)
119.5 (3)
120.1 (4)
119.9 (4)
119.2 (4)
121.0 (4)
119.1 (4)
120.1 (4)
106.5 (18)
107.9 (19)
108.7 (19)
118.9 (2)
103.3 (18)
110.7 (2)
126.3 (3)
118.8 (3)
121.3 (3)
114.1 (4)
117.2 (4)
115.4 (4)
120.7 (5)
119.3 (5)
121.1 (4)
128.6 (4)
114.8 (4)
116.2 (4)
124.7 (4)
125.7 (4)
121.3 (4)
119.0 (4)
121.1 (5)
120.3 (5)
120.4 (4)
120.4 (4)
118.8 (4)
121.1 (4)
120.1 (4)
120.8 (4)
120.2 (4)
C1C6
C3S12
C2C1C6
C3S12N13
C3S12O14
C3S12O15
O14S12O15
O14S12N13
O15S12N13
S12N13C16
C2C3S12
S12O14
S12O15
S12N13
N13C16
C16N21
C16N22
C17N22
C18N21
C17C19
C18C19
C17C23
C18C24
C6N11
N11C32
C32C34
C34C35
C34C36
C35C37
C37C39
C38C39
C36C38
C36O43
O43H44
N11…H44
O43…N11
C4C3S12
N13C16N21
N13C16N22
C16N21C18
N21C18C19
C18C19C17
C19C17N22
N21C16N22
C16N22C17
C1C6N11
1.282
1.443 (4)
1.404 (4)
1.414 (4)
1.363 (4)
1.380 (4)
1.373 (4)
1.388 (4)
1.328
C5C6N11
C6N11C32
N11C32C34
C34C36C38
C36C38C39
C37C39C38
C35C37C39
C34C35C37
C35C34C36
C32C34C35
C32C34C36
C34C36O43
O43C36C38
0.73 (5)
1.90 (4)
2.534 (3)
1.73
2.530 (5)

O43H44…N
1
46.8
142.3
146 (5)
129
1
1
a
b
c
Ref. [23]. Ref. [24]. Ref. [25].
F : Intramolecular hydrogen bonded system & F : Non-hydrogen bonded system.
I
II

Table (2): Occupancy of natural orbitals (NBOs) and hybrids calculated for the titled compound (selected).
FI
Hybrid
[AO (%) ]
FII
Hybrid
[AO (%) ]
b
b
Donor
Occupancy
Acceptor
NBOs
Donor
Occupancy
Acceptor
NBOs
Donor (i)
Acceptor (j)
c
c
9
9.99 0.35
99.99 0.42
sp
d
(N11)
sp
d
(N11)
*
π(N11-C32)
π (C5-C6)
[s(0.37)p(99.49)d(0.13)]
0.380
0.453
0.018
[s(0.56)p(99.20)d(0.24)]
0.381
0.432
0.021
1
.909
99.99 0.18
1.912
99.99 0.18
sp
d
(C32)
sp
d
(C32)
*
[s(0.35)p(99.47)d(0.18)]
[s(0.53)p(99.38)d(0.09)]
π(N11-C32) π (C34-C36)
1
.88 0
1.88 0
sp d (C34)
sp d (C34)
*
[s(34.73)p(65.24)d(0.03)]
[s(34.73)p(65.24)d(0.03)]
σ(C34-C35) σ (C36-O43)
1.972
1.570
1.708
1.91 0
1.970
1.618
1.693
1.96 0
sp d (C35)
sp d (C35)
[
s(34.38)p(65.57)d(0.04)]
[s(33.76)p(66.19)d(0.04)]
0
0
spd (C34)
spd (C34)
*
[s(0.0)p(99.99)d( 0.01)]
[s(0.0)p(99.98)d( 0.02)]
π(C34-C36) π (C35-C37)
0
0.304
0.305
0
0.282
0.310
spd (C36)
spd (C36)
[
s(0.0)p(99.96)d( 0.04)]
[s(0.0)p(99.96)d( 0.04)]
0
0
spd (C35)
spd (C35)
*
[s(0.0)p(99.95)d( 0.05)]
[s(0.0)p(99.95)d( 0.05)]
π(C35-C37) π (C38-C39)
0
0
spd (C37)
spd (C37)
[
s(0.0)p(99.96)d( 0.04)]
[s(0.0)p(99.96)d( 0.04)]
2
.76 0
2.62 0.01
*
sp
d
sp
d
LP(1)N11
LP(2)O43
σ (C32-H33)
1.848
1.805
0.034
0.453
1.876
1.863
0.044
0.432
[
s(26.57)p(73.39)d( 0.04)]
[s(27.55)p(72.31)d( 0.14)]
9
9.87 0
99.87 0.98
*
sp
d
sp
d
π (C34-C36)
[
s(0.01)p(99.87)d(0.12)]
[s(0.12)p(99.76)d(0.12)]

Table (3): The electric dipole moment, linear polarizability, and first hyperpolarizability of the titled compound, SMS.
Linear polarizability and dipole moment
First hyperpolarizability
DFT/B3LYP/6-31G(d)
FII
HF/6-31G(d)
FI
HF/6-31G(d)
FI
FI
esu
10
esu
esu
esu
a.u.
-23
a.u.
-23
a.u.
-23
a.u.
-30
×
× 10
6.29
-0.56
0.19
3.06
-0.19
3.03
4.13
3.43
× 10
5.10
-0.37
0.37
2.61
-0.09
2.90
3.53
2.54
× 10
-5.43
2.39
-1.68
-1.85
1.71
0.42
0.35
1.15
0.27
0.05
6.38
αxx
αxy
αxz
αyy
αyz
αzz
αtot
Δα
μx
431.584
39.595
17.674
203.378
25.277
207.001
280.65
242.53
-1.50
6.39
0.58
0.26
3.01
3.74
3.07
4.16
3.59
424.83
-38.41
13.17
206.55
-13.03
204.59
278.65
231.37
1.82
344.78
-25.06
25.24
176.04
-6.62
195.67
238.83
171.67
1.76
βxxx
βxxy
βxyy
βyyy
βxxz
βxyz
βyyz
βxzz
βyzz
βzzz
βtot
-628.84
277.61
-194.82
-215.12
197.99
49.26
41.38
132.94
31.38
μy
μz
-5.11
-0.29
-4.96
-1.08
-5.30
0.80
6.31
739.09
μtot
5.33
5.39
5.64

-1
-1
-1
*
Table (4): Maximum wavelengths (λmax, nm), wavenumbers (cm ), molar absorptivities (ε , L mol cm ), π-π transition energy (E ),
max
obs
and oscillator strength (f ), of SMS in different solvents.
obs
Cyclohexane
Dioxane
Ethanol
213
DMSO
Chloroform
s
s
s
λmax (nm)
220
4.54
2.99
5.64
0.63
9.22
9.54
9.06
9.28
275
3.63
2.06
5.51
0.45
8.26
8.66
8.27
8.40
246
273
4.06
1.11
5.05
0.22
8.71
9.08
8.64
8.82
275
3.63
1.97
4.51
0.47
8.25
8.67
8.27
8.40
254
276
3.62
2.08
4.50
0.38
8.24
8.56
8.26
8.39
240
274
4
10
-1
(cm
)
3.66
2.05
4.55
0.45
8.28
8.69
8.29
8.42
4.69
4.21
5.83
0.79
9.38
9.69
9.19
9.42
3.93
1.11
4.88
0.22
8.57
8.96
8.53
8.69
4.16
1.07
5.17
0.22
8.82
9.18
8.73
8.91
3.64
1.87
4.53
0.45
8.27
8.68
8.28
8.41
×
4
εmax × 10
Eobs (eV)
fobs
st
*
I (eV) (1 method)
P
nd
**
I (eV) (2 method)
P
rd
***
I (eV) (3 method)
P
Mean I (eV)
P
s:shoulder
IP = a + bEobs (a = 4.93 and b = 0.857), ** (a = 5.156 and b = 0.778), *** (a = 5.11 and b = 0.701)
*

1
Table (5): Experimental and calculated H NMR chemical shifts for the title compound
δ Calcd.
FI
FII
δ Exp.
Atom
DFT/B3LYP/6-311+G(2d,p)
HF/6-31G(d)
DFT/B3LYP/6-311+G(2d,p)
Gaseous
7.62
8.34
8.96
7.40
6.68
2.02
2.42
2.66
2.02
2.53
2.42
6.92
8.90
7.08
7.31
7.62
12.72
DMSO
7.82
8.35
8.94
7.73
7.02
2.28
2.50
2.66
2.28
2.50
2.41
7.08
9.11
7.29
7.35
7.82
12.75
Gaseous DMSO
Gaseous
7.61
8.31
8.93
7.12
6.69
2.01
2.48
2.67
2.01
2.58
2.42
6.97
8.85
7.25
7.25
7.72
5.55
DMSO
7.73
8.31
8.92
7.46
7.04
2.26
2.55
2.66
2.26
2.55
2.43
7.12
9.04
7.38
7.38
7.92
6.12
DMSO
H7
H8
H9
7.49
8.55
9.14
7.22
6.27
1.96
2.49
2.74
1.90
2.59
2.49
6.22
8.90
6.97
7.22
7.94
11.99
7.66
8.56
9.12
7.66
6.66
2.22
2.56
2.72
2.22
2.56
2.49
6.42
9.22
7.22
7.22
8.20
12.02
m
6.5-7.79
H10
H20
H25
H26
H27
H28
H29
H30
H31
H33
H40
H41
H42
H44
6.51
2.19
2.19
11.10
8.93
m
6
6
.5-7.79
12.50
m
.5-7.79
H45
7.62
7.91
7.79
8.20
8.64
8.63
m: means multiplet and overlapped with other aromatic protons.