Chemical Physics Letters 423 (2006) 131–137

www.elsevier.com/locate/cplett

Effect of C–H    S and C–H    Cl interactions on the

conformational preference of inhibitors of TIBO family
Renato F. Freitas, Sérgio E. Galembeck *

Departamento de Quı́mica, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Aveinda Banderiantes
3900, 14040-901 Ribeirão Preto-SP, Brazil

Received 7 December 2005; in final form 13 March 2006

Available online 22 March 2006

Abstract

The non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) are an important class of drugs employed in antiviral ther-
apy. The coordinates of three inhibitors, derived from TIBO, tetrahydroimidazo-(4,5,1-1-jk)(1,4)-benzodi-azepin-2(1H)-one, (which
belongs to the NNRTIs class), were taken from PDB database and the electronic structure were investigated by using the B3LYP/6-
31+G(d,p) model. Results obtained by means of the natural bond orbital (NBO) and atoms in molecules (AIM) methods indicated
the presence of weak hydrogen bonds of the C–H    S and C–H    Cl type, which are partially responsible for the conformational dif-
ferences observed between the inhibitors 8 Cl-TIBO and 9 Cl-TIBO.
 2006 Elsevier B.V. All rights reserved.

1. Introduction Two of the commonest mutations that make HIV-1 resis-

HIV-1 reverse transcriptase enzyme (HIV-1 RT) is a key
target of anti-AIDS therapy because it catalyzes an essen-
tial step in virus replication: the conversion of viral geno-
mic RNA into proviral DNA, which later integrates the
host genome [1]. There are two classes of HIV-1 RT inhib-
itors: the nucleoside (NRTIs) and the non-nucleoside ones
(NNRTIs). NRTIs act on the catalytic site of the reverse
transcriptase enzyme, preventing DNA synthesis, whereas
NNRTIs bind non-competitively to a hydrophobic site
close to the catalytic site, forcing the enzyme to adopt an
inactive conformation. [2].
Three NNRTIs are currently being used in anti-HIV
treatment, namely nevirapine, delavirdine, and efavirenz
[2]. The ‘first-generation’ inhibitors a-APA, TIBO 86183,
9 Cl-TIBO, and nevirapine promote fast mutations of the
enzyme. These mutations make the virus resistant to these
inhibitors because the interaction of these NNRTIs with
aminoacids from the allosteric site of HIV-1 RT is similar.
*
Corresponding author. Fax: +55 16 3602 4838/633 8151.
E-mail address: segalemb@usp.br (S.E. Galembeck).
tant to NNRTIs are Lys103Asp and Tyr181Cys [1]. Many
efforts have been made toward novel NNRTIs that are
resilient to such drug resistance mutations. To this end,
new compounds such as capravirine, DPC and TMC 125
have been obtained. These compounds have led to satisfac-
tory results regarding inhibition of HIV-1 RT exhibiting
one or more punctual mutations [3–5].
Compounds of TIBO family were the first to be shown
to have high power and specificity toward the inhibition
of HIV-1 replication [6]. Since then, these compounds have
been extensively studied with a view to increasing their
power and understanding the mechanism of action of
NNRTIs [7,8]. Conformational analysis of compounds of
TIBO family has been carried out in order to assess the role
played by the structure of these compounds in the inhibi-
tion of HIV-1 RT [9,10]. These studies have shown that
the bioactive conformation is not a global minimum, and
they have indicated that the compounds of TIBO family
present high flexibility, which allows them to adjust to
the allosteric site of the enzyme [9,10].
In this Letter, an analysis of the intramolecular interac-
tions taking place in 8 Cl-TIBO and 9 Cl-TIBO originally

0009-2614/$ - see front matter  2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.cplett.2006.03.041
132 R.F. Freitas, S.E. Galembeck / Chemical Physics Letters 423 (2006) 131–137
complexed with wild-type HIV-1 RT, and in 8 Cl-TIBO
complexed with the Tyr181Cys HIV-1 RT mutant will be
presented, by means of the natural bond orbital (NBO)
[11] and atoms in molecules (AIM) [12] methods. This
study was carried out aiming at understanding the different
conformational preferences exhibited by these molecules.
Our results indicate that interactions of the C–H    S
and C–H    Cl type are partially responsible for the diver-
sity in the observed conformations.
2. Computational methods
In this work, three crystalline structures of the HIV-1
RT enzyme, deposited in the Protein Data Bank (PDB)
[13] and complexed with inhibitors of TIBO family were
used. The first structure contained the inhibitor 8 Cl-TIBO
(R86183) complexed with wild-type HIV-1 RT (1HNV),
the second structure contained 8 Cl-TIBO complexed with
the enzyme exhibiting two punctual mutations, Tyr181Cys
in subunit p66 and Cys280Ser in subunit p51 (1UWB) [8],
and the third consisted of the inhibitor 9 Cl-TIBO
(R82913) complexed with wild-type HIV-1 RT (1REV) [9].
The inhibitors were extracted from the complexes by
means of the RASMOL software [14]. Hydrogen atoms were
then added by using the BABEL software [15], and the struc-
tures of the compounds were verified (Fig. 1).
From the structures obtained in the previous stage, the
positions of the added atoms were optimized by the HF/
6-31+G(d,p) model. Improving the method or the basis
set produces only minor changes in the positions of the
added atoms. The NBO and AIM methods was used for
the electronic density analysis with the B3LYP/6-
Fig. 1. Numbering of the atoms in the inhibitors studied herein. The number in brackets refers to the numbering of the chlorine atom in 9 Cl-TIBO.
31 + G(d,p) model [16]. Calculations were carried out by
using the softwares GAUSSIAN98 [17], NBO5.0 [18], and
AIM2000 [19]. Structures were superposed and visualized
by means of the software CHIMERA [20].
3. Results and discussion
The inhibitors studied in this work were designated T1
(wild 8 Cl-TIBO), T2 (mutant 8 Cl-TIBO), and T3 (9 Cl-
TIBO). Bond lengths and angles vary slightly among the
inhibitors, (Tables S1 and S2). As for bond lengths, the
widest variations are 0.103 and 0.017 Å for the heavy and
hydrogen atoms, respectively. The widest variation
observed in bond angles is 13.9 for C(18)–C(19)–C(20),
in a comparison between T1 and T3. In contrast, the dihe-
dral angles of the seven-membered rings, and methyl and
dimethylalyl substituents also vary significantly, as can be
seen from the superposition of the structures, (Fig. 2 and
Table 1). These differences can be attributed to the different
stable conformations that the molecules exhibit due to the
different positions of the chlorine atom in the isomers, as
well as to interactions with the aminoacids on the binding
pocket. In inhibitor T3, the seven-membered ring is almost
coplanar with the benzimidazole ring, and the angle
between the methyl and dimethylalyl groups [C(16)–C(8)–
N(9)–C(17)] is 161.4. A comparison between the dimethyl-
alyl and methyl groups on the structures of T1 and T2 with
these same groups on T3 shows that they are near perpen-
dicularly oriented. Contrary to T3, T1 and T2 have very
similar conformations, and the conformation of the
seven-membered ring is a half-chair. This indicates that
the conformation of the inhibitor is heavily dependent on
 R.F. Freitas, S.E. Galembeck / Chemical Physics Letters 423 (2006) 131–137 133

p ! p* n ! p*, and n ! r* type take place. The p ! p*,

np Nð1Þ ! pCð2ÞCð6Þ , and np Nð5Þ ! pCð2ÞCð6Þ interactions
indicate the resonance in the benzimidazole ring. It can be
seen that there is p backdonation from the chlorine atom
to the benzoimidazole ring, np Clð13Þ ! pCð11ÞCð12Þ , as well
as conjugation of the thiourea group, np Nð1Þ !
pCð3ÞSð4Þ and np Nð5Þ ! pCð3ÞSð4Þ . These are the most intense
interactions encountered in these compounds, specially in
T3. Although the electronegativity of the sulfur atom is mod-
erate, the resonance of the thiourea group increases the effec-
tive electronegativity of this atom significantly, making it a
good proton acceptor [21]. This leads to stabilization of the
interactions between non-chemically bonded atoms and also
of the intramolecular interactions np Sð4Þ ! rCð7ÞHð23Þ in T1
and T2, and np Sð4Þ ! rCð7ÞHð24Þ in T3, (Fig. 3A). Despite
being relatively little studied, several papers indicate that
Fig. 2. Superposition of the inhibitors from the TIBO family: T1 (blue), C–H    S interactions are weak hydrogen bonds that have
T2 (green), and T3 (yellow), using benzimidazole ring as reference. great importance in the design of supramolecular organic
systems and in molecular stacking [22,23].
Table 1 There is another intramolecular interaction np Clð13Þ !
Dihedral angles presenting the widest variations () rCð10ÞHð26Þ in T1 and T2, (Fig. 3B). To date, there is no con-
Dihedral angle T1 T2 T3 sensus on whether interactions of the C–H    Cl type are
C(7)–C(8)–N(9)–C(10) 30.3 40.4 93.0 hydrogen bonds. Apparently, interactions of the C–
C(8)–N(9)–C(10)–C(11) 90.9 85.5 91.1 H    Cl and C–H    Cl–M, (M = metal), type can be
N(5)–C(7)–C(8)–C(16) 159.4 144.8 68.3 considered hydrogen bonds, whereas C–H    Cl–C inter-
C(7)–C(8)–N(9)–C(17) 180.0 168.6 73.9
actions would hardly be taken as such without activation
C(8)–N(9)–C(17)–C(18) 111.9 121.8 174.4
of the acceptor via formation of an anion or by coordina-
tion to a metal [24]. Nevertheless, C–H    Cl interactions
the position of the chlorine atom, making it also dependent have shown to be of great importance in several areas such
on intramolecular interactions. Interactions between the as molecular recognition, reactivity and structure of bio-
inhibitor and aminoacids on the binding pocket should chemical species, stability of metal complexes, crystal engi-
alter the preferential conformation only slightly. neering, and determination of molecular conformations
The conformational analysis of a TIBO derivative [25–29].
(R82913) was carried out in this laboratory by means of In the case of inhibitor T3, there is no evidence that an
the pseudosystematic method SUMM [9]. The conformers interaction takes place between the lone electron pair of
were grouped by using the clustering technique, according the chlorine atom and the hydrogen atom present on the
to the folding of the seven-membered ring and to the position seven-membered ring, because the position of the chlorine
of the dimethylalyl group. Results showed that the com- atom hinder such interaction. Furthermore, the np Sð4Þ !
plexed structure of the inhibitor TIBO R82913 is equivalent rCð7ÞHð24Þ interaction in T3 is weaker than that in T1 and
to that of the conformer SP5. The inhibitors T1 and T2 can T2. These results indicate that T3 experiences more confor-
also be classified as SP5, while T3 does not fit into any of mational freedom, allowing the seven-membered ring to
the classes obtained in the clustering analysis. adopt a quasiplanar conformation in relation to the benz-
imidazole ring.
4. NBO Analysis
5. Natural atomic charges
The second-order perturbation energies, (DE(2)), of equiv-
alent interactions between NBOs in the three inhibitors are The natural atomic charges obtained by the NPA
similar, (Tables 2 and S4). In all cases, interactions of method are very similar in the three inhibitors, (Table S5).

Table 2
Second-order perturbation energy (DE(2)) of the most relevant interactions taking place in inhibitors from the TIBO family, (kcal/mol)
T1 T2 T3
Interaction DE(2) Interaction DE(2) Interaction DE(2)
np Nð1Þ ! pCð3ÞSð4Þ 46.40 np Nð1Þ ! pCð3ÞSð4Þ 56.68 np Nð1Þ ! pCð3ÞSð4Þ 71.54
  
np Nð5Þ ! pCð3ÞSð4Þ 53.97 np Nð5Þ ! pCð3ÞSð4Þ 71.08 np Nð5Þ ! pCð3ÞSð4Þ 75.48
  
np Sð4Þ ! rCð7ÞHð23Þ 3.77 np Sð4Þ ! rCð7ÞHð23Þ 3.65 np Sð4Þ ! rCð7ÞHð24Þ 1.03
 
np Clð13Þ ! rCð10ÞHð26Þ 2.49 np Clð13Þ ! rCð10ÞHð26Þ 2.47
134 R.F. Freitas, S.E. Galembeck / Chemical Physics Letters 423 (2006) 131–137

interactions S(4)    H(23), (1); Cl(13)    H(26), (2);

Fig. 3. Interactions in inhibitor T1: (A) np Sð4Þ ! rCð7ÞHð23Þ ; (B)
np Clð13Þ ! rCð10ÞHð26Þ .
The largest differences are related to the different locations
of the chlorine atom in the isomers and they can be
observed between the carbon atoms and the chlorine atom
in T1 and T3, (Table 3). The hydrogen atoms involved in
hydrogen bonding, H(23) and H(26) in T1 and T2, and
H(24) in T3, are the atoms with the highest positive charges.
6. AIM analysis
The various properties of BCPs are similar, (Tables 4
and S6). The molecular graphs for T1 show four bond
paths that indicate the occurrence of the intramolecular
H(27)    H(32), (3); and H(34)    H(41), (4), (Fig. 4A).
For all the four BCPs qr and L(r) fall in the range proposed
by Popelier to characterize a hydrogen bond [30]. Both
H    H interactions are traditionally considered as steric
repulsions, but Matta et al. demonstrated that these H–H
bonds substantially stabilize the system. [31] These authors
propose several criteria for these bonds. The nature of all
intramolecular interactions can be understood by e and
the distance between the BCP and the RCP, (Tables 4
and 5). A high e indicates that the interaction is structurally
unstable since the BCP may be destroyed upon its binding
to the RCP [32]. Therefore, the e value shows how stable a
system is in the face of a geometry variation in the system
[30]. By analyzing the results for (3) and (4) it is possible to
observe that e is higher than the suggested threshold,
qb = qr and BCP–RCP distances are small. By comparing
the integrated properties for the atoms involved in
H    H interaction with similar hydrogens it is possible
to observe that the energetic stabilization and the charge
variations are very small, around 2.0 kcal/mol and 0.001,
but Gb is larger than jVbj. It can be concluded that, despite
the disagreement of some parameters with the criteria pro-
posed by Matta et al., the observed H    H interactions are
attractive H–H bonds, but the associated bond paths are
very close to instability. As for interactions (1) and (2), they
have low e and moderate BCP–RCP distance. Domagala
et al. have observed the existence of intramolecular interac-
tions of the C–H    S type in some thiazolidinic com-
pounds, where the qr and L(r) values are close to those
found in this work [33]. According to these authors, the
C–H    S interaction may be regarded as a weak hydrogen
bond. The presence of the interactions C(7)–H(23)    S(4)
and C(10)–H(26)    Cl(13) as confirmed by the AIM anal-
ysis are in agreement with the results obtained during the
NBO analysis, which showed that these interactions could
be partially responsible for the conformational preference
observed in T1 and T2.

Table 3
NPA charges exhibiting the widest variations among the monomers T1, T2, and T3
T1 T2 T3
Átom Charge Átom Charge Átom Charge
N(1) 0.611 N(1) 0.606 N(1) 0.574
S(4) 0.212 S(4) 0.223 S(4) 0.263
C(6) 0.144 C(6) 0.153 C(6) 0.177
C(11) 0.033 C(11) 0.041 C(11) 0.072
C(12) 0.062 C(12) 0.072 C(12) 0.248
Cl(13) 0.011 Cl(13) 0.020 C(13) 0.086
C(14) 0.248 C(14) 0.251 Cl(14) 0.036
C(15) 0.254 C(15) 0.254 C(15) 0.282
C(16) 0.700 C(16) 0.698 C(16) 0.720
C(19) 0.037 C(19) 0.035 C(19) 0.010
H(23) 0.300 H(23) 0.300 H(23) 0.256
H(24) 0.245 H(24) 0.244 H(24) 0.275
H(26) 0.261 H(26) 0.263 H(26) 0.239
H(27) 0.224 H(27) 0.227 H(27) 0.261
H(31) 0.236 H(31) 0.237 H(31) 0.259
 R.F. Freitas, S.E. Galembeck / Chemical Physics Letters 423 (2006) 131–137 135

Table 4
Intramolecular BCP properties for T1, T2, and T3, qr, and L(r) in a.u.
Interaction T1 T2 T3
qr L(r) e qr L(r) e qr L(r) e
S(4)    H(23) 0.019 0.015 0.394 0.019 0.015 0.357
Cl(13)    H(26) 0.017 0.016 0.336 0.017 0.016 0.331
C(16)    H(27) 0.026 0.026 0.131
H(27)    H(32) 0.015 0.015 0.886 0.021 0.019 0.387
H(26)    H(35) 0.021 0.019 0.291
H(34)    H(41) 0.010 0.011 1.384

Three of the four BCPs present in T1 can also be
observed in T2: between S(4) and H(23), Cl(13) and
H(26), and H(27) and H(32). These BCPs have qr and
L(r) lying in the range proposed by Popelier. Interaction
(3) exhibits low e and moderate BCP–RCP distance. All
results for the critical point and integrated properties are
similar to the observed for interactions (3) and (4) in T1,
with indicate that this interaction is an attractive H–H
bond. As for interactions (1) and (2), which are also
observed in T1, they can be seen as an indication of the
existence of weak intramolecular hydrogen bonds of the
C–H    S and C–H    Cl type, (Figure S1).
As for T3, none of the intramolecular interactions previ-
ously observed for T1 and T2 were found, (Fig. 4B). Only
two interactions can be seen: C(16)    H(27) and
H(26)    H(35), which have qr and L(r) falling within the
range proposed by Popelier for hydrogen bond formation.
Despite exhibiting moderate BCP–RCP distances and low
e, the bond paths in T3 are curved. Because it is observed
a bond path, an energetic stabilization and an increase in
the electronic densities in the atoms involved in these inter-
molecular bonds, both interactions are attractive ones.
Various researchers have proposed the use of another
parameter besides L(r) to distinguish between intra or
intermolecular interactions with partial covalent character,
or open shell, and purely closed shell interactions, such as
van Der Waals or ionic interactions [33,34]. This other
parameter is the total energy density in the BCP, H(r),
which is given by the following equation:
H ðrÞ ¼ GðrÞ þ V ðrÞ ð1Þ
where G(r) and V(r) correspond to the kinetic and potential
energies densities, respectively. In a covalent or partially
covalent interaction, V(r), which is always negative, is lar-
ger in terms of absolute value than G(r), which is positive
for any interaction. Consequently, H(r) is negative. In
interactions with a closed shell character only, jG(r)j is lar-
ger than jV(r)j, so H(r) should be positive [34] (Table 6).
Analysis of these parameters indicates that the interac-
tions S(4)    H(23) and Cl(13)    H(27) can be considered

Table 5
BCP–RCP distances, in Å
Interaction T1 T2 T3
S(4)    H(23) 0.389 0.411
Fig. 4. Molecular graphs for (A) T1, and (B) T3. (A): (1) BCPS(4)  H(23); Cl(13)    H(26) 0.415 0.416
(2) BCPCl(13)  H(26); (3) BCPH(27)  H(32); (4) BCPH(34)  H(41). (B): (1) C(16)    H(27) 0.489
BCPC(16)  H(27); (2) BCPH(26)  H(35). Atoms are indicated by spheres and H(27)    H(32) 0.282 0.521
the critical points by dots. BCP are red points and RCP are the yellow H(26)    H(35) 0.658
ones. H(34)    H(41) 0.251
136 R.F. Freitas, S.E. Galembeck / Chemical Physics Letters 423 (2006) 131–137
Table 6
G(r), V(r), and H(r), (·103 a.u.), for T1, T2, and T3
Interaction T1
G(r) V(r) H(r)
S(4)    H(23) 13.777 12.329 1.448
Cl(l3)    H(26) 13.712 11.312 2.399
C(16)    H(27)
H(27)    H(32) 12.598 9.757 2.841
H(26)    H(35)
H(34)    H(41) 8.169 5.634 2.534
weak hydrogen bonds, since L(r) < 0 and H(r) > 0. These
results are in agreement with the work of Rozas et al, who
propose that weak hydrogen bonds exhibit L(r) < 0 and
H(r) > 0, intermediate hydrogen bonds present L(r) < 0
and H(r) < 0, and strong hydrogen bonds have L(r) > 0
and H(r) < 0 [35]. However, H(r) > 0 indicates that all the
intramolecular interactions observed in the compounds
studied herein are purely of the closed shell type, with no
covalent character. This fact reinforces the conclusion that
the hydrogen bond of the C–H    S type is weak, since the
strongest hydrogen bonds present small covalent character.
7. Conclusions
Analysis of the intramolecular interactions of two inhib-
itors of TIBO family (8 Cl-TIBO and 9 Cl-TIBO) extracted
from three crystalline structures of complexes formed
between these inhibitors and HIV1 RT was carried out
by means of the NBO and AIM methods. It can be
observed that 8 Cl-TIBO and 9 Cl-TIBO present different
conformations. This indicates that the intramolecular inter-
actions determine the conformation of these molecules,
while the intermolecular interactions act by only distorting
the preferential conformation. The presence of interactions
of the C–H    S and C–H    Cl type was observed in 8
Cl-TIBO, T1 and T2. The former interaction may be
considered a weak hydrogen bond, and both interactions
contribute to the stabilization of the observed conforma-
tions. 9 Cl-TIBO does not display the C–H    Cl interac-
tion because of the position of the chlorine atom, and the
NBO and AIM analyses showed that the hydrogen bond
C–H    S is relatively weaker in this inhibitor than in 8
Cl-TIBO. The absence of the former interaction and the
low intensity of the latter, if compared with the same in
T1 and T2, render 9 Cl-TIBO greater conformational free-
dom, which allows the seven-membered ring of this inhib-
itor to adopt a conformation that is approximately
coplanar with the benzimidazole ring.
Appendix A. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/
j.cplett.2006.03.041.
T2 T3
G(r) V(r) H(r) G(r) V(r) H(r)
13.390 12.013 1.377
13.860 11.458 2.402
24.084 21.776 2.309
16.996 15.022 1.974
17.120 15.214 1.906
References
[1] J. Ren, R. Esnouf, A. Hopkins, C. Ross, Y. Jones, D. Stammers, D.
Stuart, Structure 3 (1995) 915.
[2] E. De Clercq, J. Med. Chem. 48 (2005) 1297.
[3] J. Ren, C. Nichols, L.E. Bird, T. Fujiwara, H. Sugimoto, D.I. Stuart,
D.K. Stammers, J. Biol. Chem. 275 (2000) 14316.
[4] J.W. Corbett, K.J. Kresge, S. Pan, B.C. Cordova, R.M. Klabe, J.D.
Rodgers, S.K.E. Viitanen, Antimicrob. Agents 43 (1999) 2893.
[5] J. Guillemont, E. Pasquier, P. Palandjian, D. Vernier, S. Gaurrand,
P.J. Lewi, J. Heeres, M.R. de Jonge, L.M.H. Koymans, F.F.D.
Daeyaert, M.H. Vinkers, E. Arnold, K. Das, R. Pauwels, K. Andries,
M.P. de Bethune, E. Bettens, K. Hertogs, P. Wigerinck, P. Timm-
erman, P.A.J. Janssen, J. Med. Chem. 48 (2005) 2072.
[6] R. Pauwels, K. Andries, J. Desmyter, D. Schols, M. Kukla, H.
Breslin, A. Raeymaekers, J.V. Gelder, R. Woestenborghs, J. Heyk-
ants, K. Schellenkens, M.A.C. Janssen, E. De Clercq, P. Janssen,
Nature 343 (1990) 470.
[7] W. Ho, M. Kukla, H. Breslin, D. Ludovici, P. Grous, C. Diamond,
M. Miranda, J. Rodgers, C. Ho, E. De Clercq, R. Pauwels, K.
Andries, M.A.C. Janssen, P. Janssen, J. Med. Chem 38 (1995) 794.
[8] K. Das, J. Ding, Y. Hsiou, A.D. Clark, H. Moereels, L. Koymans, K.
Andries, R. Pauwels, P.A. Janssen, P.L. Boyer, P. Clark, R.H. Smith,
M.B.K. Smith, c.J. Michejda, S.H. Hughes, E. Arnold, J. Mol. Biol.
264 (1996) 1085.
[9] O.J. Abrahão, P.G.B.D. Nascimento, S.E. Galembeck, J. Comput.
Chem. 22 (2001) 1817.
[10] S. Saen-oon, S. Hannonguba, P. Wolschann, J. Chem. Inf. Comput.
Sci. 43 (2003) 1412.
[11] A.E. Reed, R.B. Weinstock, F.J. Weinhold, J. Chem. Phys. 83 (1985)
735.
[12] R.F.W. Bader, Atomns in Molecules – A Quantum Theory, Inter-
national Series of Monographs on Chemistry, vol. 22, Oxford
University Press, Oxford, 1990.
[13] H.M. Berman, J. Westbrook, Z. Feng, Z.G. Gilliland, T.N. Bhat, H.
Weissig, I.N. Shindyalov, P.E. Bourne, Nucl. Acid Res. 28 (2000) 235.
[14] R. Sayle, Molecular Graphics Visualization Tool, Glaxo Research
and Development, Greeford, Middlesex, UK, 1994.
[15] J.J. Gosper, BabelWin A Molecular Structure Information Inter-
change Hub, Brunel University, 1998.
[16] C. Lee, W. Yang, R.G. Parr, Phys. Rev. B 37 (1988) 785.
[17] M.J. Frisch et al., GAUSSIAN 98, Revision A.9, Gaussian Inc.,
Pittsburgh PA, 1998.
[18] E.D. Glendening, J.K. Badenhoop, A.E. Reed, J.E. Carpenter, J.A.
Bohmann, C.M. Morales, F. Weinhold, NBO 5.0, Theoretical
Chemistry Institute, University of Wisconsin, Madison, WI, 2001.
[19] F. Biegler-König, J. Schönbohm, D. Bayles, J. Comput. Chem. 22
(2001) 545.
[20] E.F. Pettersen, T.D. Goddard, C.C. Huang, G.S. Couch, D.M.
Greenblatt, E.C. Meng, T.E. Ferrin, J. Comput. Chem. 25 (2004)
1605.
[21] F. Allen, C.M. Bird, R.S. Rowland, P.R. Raithby, Acta Cryst. B53
(1997) 680.
 R.F. Freitas, S.E. Galembeck / Chemical Physics Letters 423 (2006) 131–137
[22] S.J. Narayanan, B. Sridevi, T.K. Chandrashekar, A. Vij, R. Roy, R.
Angew, Chem. Int. Ed. 37 (1998) 3394.
[23] M.J. Potrzebowski, M. Michalska, A.E. Koziol, S. Kazmierski, T.
Lis, J. Pluskowski, W. Ciesielski, J. Org. Chem. 63 (1998) 4209.
[24] C.B. Aakeröy, T.A. Evans, K.R. Seddon, I. Pálinko, New J. Chem. 23
(1999) 145.
[25] E.M.D. Keegstra, A.L. Spek, J.W. Zwikker, L.W. Jenneskens, J.
Chem. Soc. Chem. Commun. 14 (1994) 1633.
[26] Z.S. Derewenda, L. Lee, U. Derewenda, J. Mol. Biol. 252 (1995) 248.
[27] T. Steiner, W. Saenger, J. Chem. Soc. Chem. Commun. 20 (1995)
2087.
[28] V. Balamurugan, W. Jacob, J. Mukherjee, R. Mukherjee, Cryst. Eng.
Commun. 6 (2004) 396.
137
[29] G. Müller, M. Lutz, S. Harder, Acta Crystallog. 52 (1996) 1014.
[30] P. Popelier, Atoms in Molecules: An Introduction, Prentice Hall,
England, 2000.
[31] C.F. Matta, J. Hernández-Trujillo, T.-H. Tang, R.F.W. Bader,
Chem. Eur. J. 9 (2003) 1940.
[32] D. Cremer, E. Kraka, T.S. Slee, R.F.W. Bader, C.D.H. Lau,
T.T.N. Ding, P.J. MacDougall, J. Am. Chem. Soc. 105 (1983)
5069.
[33] M. Domagala, S.J. Grabowski, K. Urbaniak, G. Mloston, J. Phys.
Chem. A 107 (2003) 2730.
[34] S.J. Grabowski, J. Phys. Org. Chem. 17 (2004) 18.
[35] I. Rozas, I. Alkorta, J. Elguero, J. Am. Chem. Soc. 122 (2000)
11154.