Thiazole-carbonyl interactions: A case study using phenylalanine thiazole cyclic tripeptides

Article abstract of DOI:10.1021/cg301147s

Natural as well as synthetic thiazole/oxazole peptides have shown widespread pharmacological and metal binding properties. Herein, phenylalanine- and tyrosine derived thiazole-containing cyclic tripeptides were synthesized, and the influence of the solvent on the supramolecular assembly in the solid state was investigated. Striking influences of the solvent on the solid state structure were observed. S...O interactions between the sulfur of a thiazole ring and a carbonyl moiety of an amide showing an average distance of 3.1 A which is much smaller than the sum of the van der Waals radii predominantly mediate the crystal structure. To get deeper insights into this kind of interaction, two model systems consisting of thiazole and acetyl-N-methylamide were studied using the MP2/6-311G++(3df,3dp) level of theory. Theoretical calculations revealed that these interactions are associated with an average energy gain of about 16 kJ/mol in comparison with the separated species.

Full text of DOI:10.1021/cg301147s

Article
pubs.acs.org/crystal
Thiazole−Carbonyl Interactions: A Case Study Using Phenylalanine
Thiazole Cyclic Tripeptides
Sachitanand M. Mali,† Tobias F. Schneider,‡ Anupam Bandyopadhyay,† Sandip V. Jadhav,†
Daniel B. Werz,*,‡ and Hosahudya N. Gopi*,†
†Department of Chemistry, Indian Institute of Science Education and Research, Sai Trinity Building, Garware Circle, Pashan,
Pune-411021, India
‡Instiut fur Organische und Biomolekulare Chemie der Georg-August-Universitat Gottingen, Tammannstr. 2, D-37077 Gottingen,
̈
̈
̈
̈
Germany
S
* Supporting Information
ABSTRACT: Natural as well as synthetic thiazole/oxazole pep-
tides have shown widespread pharmacological and metal binding
properties. Herein, phenylalanine- and tyrosine derived thiazole-
containing cyclic tripeptides were synthesized, and the influence
of the solvent on the supramolecular assembly in the solid state
was investigated. Striking influences of the solvent on the solid
state structure were observed. S···O interactions between the
sulfur of a thiazole ring and a carbonyl moiety of an amide
showing an average distance of 3.1 Å which is much smaller
than the sum of the van der Waals radii predominantly mediate the crystal structure. To get deeper insights into this kind of
interaction, two model systems consisting of thiazole and acetyl-N-methylamide were studied using the MP2/6-311G++(3df,3dp)
level of theory. Theoretical calculations revealed that these interactions are associated with an average energy gain of about
16 kJ/mol in comparison with the separated species.
A plethora of azole-based cyclic peptides isolated from marine
organisms have been reported in the past decade.11 The broad
spectrum of pharmacological properties of these secondary meta-
bolites and the ability to bind metals and to host small molecules
have fascinated synthetic as well as natural product chemists.12,13
A unique and very little explored property of thiazole/oxazole
cyclic peptides is the projection of the side chains at one face of
the molecule. Nevertheless, Fairlie et al. have shown the effective
utilization of side chain orientations in the design of a variety of
functional molecules and molecular shapes.14 However, there is
no clear understanding of the molecular behavior of these cyclic
peptides containing heterocyclic amino acids in solvents. Such
investigations may provide new opportunities to build various
molecular architectures, polymorphs, and biomaterials. Herein,
we report remarkable supramolecular architectures in the crystal
structures of thiazole-containing cyclic tripeptides directed from
polar protic, polar aprotic, and nonpolar solvents. In all structures
special motifs based on intermolecular chalcogen−chalcogen
interactions containing the thiazole moiety play a crucial role.
INTRODUCTION
■
The influence of solvents on the rates of chemical reactions
and chemical equilibria has been extensively investigated and
has become a central discipline of physical organic chemistry.
Studies on solvent−solute interactions reveal that solvopho-
bicity might play a significant role in driving flexible molecules
into compact conformations.1,2 The solvent and noncovalent
interactions play a pivotal role in the self-assembly of β-amyloid
peptides.3 The formation of well-ordered supramolecular
assemblies of peptides guided by noncovalent interactions has
been utilized in the design of peptide nanotubes, nanofibrils,
and nanospheres.4,5 Applications of these peptide nanostruc-
tures have been recognized in various fields from antimicrobial
agents, regeneration of bone and enamel, cartilage, wound-
healing, cardiovascular therapies to molecular electronics.6
Thus, the selection of an appropriate solvent or solvent mixture
is of paramount importance in physical processes such as self-
assembly of molecules, recrystallization, chromatographic separa-
tions, and catalytic reactions by phase-transfer catalysts, just
to name a few. The strengths of solvent−solute interactions
depend on a variety of intermolecular forces such as hydrogen
bonds, ionic interactions, π···π interactions, dipole−dipole,
lone pair···π, and other noncovalent interactions.7,8 Recently,
chalcogen−chalcogen9 interactions have also gained interest
across various disciplines. These noncovalent forces are often
responsible for molecular recognition events and supramole-
cular assemblies of compounds containing sulfur, selenium, or
tellurium.10
EXPERIMENTAL SECTION
General Methods. Phenylalanine, tyrosine, DCC, Lawesson’s
reagent, ethyl bromopyruvate, trifluoroacetic anhydride, trifluoroacetic
acid, N-hydroxy succinamide, 2,6-lutidine, BOP-Cl, DME, and DIPEA
■
Received: August 9, 2012
Revised: September 20, 2012
Published: September 21, 2012
© 2012 American Chemical Society
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were used as commercially available. THF was dried over sodium and
distilled prior to use. Column chromatography was performed on silica
gel (100−200 mesh). 1H and 13C NMR were recorded on a 400 MHz
instrument (100 MHz for 13C) using the residual solvent signals as an
internal reference. The chemical shifts (δ) are reported in ppm and
coupling constants (J) are given in Hz. IR spectra were recorded on
FT-IR spectrophotometer using KBr pellet. High-resolution mass
spectra were obtained from an ESI-TOF MS spectrometer.
Scheme 1. Synthesis of Thiazole-Containing Cyclic
Tripeptides 4 and 6, Respectively
(S)-Ethyl 2-(1-(tert-Butoxycarbonylamino)-2-phenylethyl)-
thiazole-4-carboxylate (Ethyl Ester of Boc-Phenylalanine
Thiazole 2). 4.38 g (15.6 mmol) of Boc-phenylalanine thioamide
1 in DME (80 mL) was cooled to −16 °C. To this solution 12.50 g
(124 mmol) of solid KHCO3 was added under nitrogen atmosphere.
The reaction mixture was stirred for another 20 min prior to the addition
of 9.73 g (49.9 mmol) of ethyl bromopyruvate. The reaction mixture was
stirred at the same temperature for about 30 min and then at room
temperature for another 30 min. The reaction mixture was cooled
to −16 °C, and then the solution of trifluoroacetic anhydride (8.7 mL,
63 mmol) and 2,6-lutidine (15 mL, 129 mmol) in DME (25 mL) was
added in a dropwise manner. The reaction mixture was allowed to
reach room temperature and stirred for another 12 h. After the
completion of the reaction, volatiles were evaporated under reduced
pressure. The reaction mixture was diluted with water and extracted
with chloroform (3 × 50 mL). The combined organic layer was
washed with brine and dried over anhydrous Na2SO4. The organic
layer was concentrated under reduced pressure and purified by silica
gel column chromatography using 20% EtOAc/petroleum ether
to afford 2 as a yellowish solid (5.2 g, 89%), mp = 82−84 °C; UV
20
(λmax) = 235 nm; [α]D + 9.32 (c = 1, MeOH); IR ν (cm−1) 3352,
2979, 1729, 1693, 1514, 1368, 1251, 1212, 1169, 1093, 1022, 854, 744;
1H NMR (400 MHz, CDCl3) δ 8.04 (s, 1H, CH (thiazole)), 7.28−
7.22 (dd, 3H, J = 8.3 Hz, 3 × CH (phenyl)), 7.11−7.09 (d, 2H, J = 6.4
Hz, 2 × CH (phenyl)), 5.30 (br., 2H, 1 × NH (Boc), 1 × CH), 4.46−
4.40 (q, 2H, J = 6.9 Hz, OCH2CH3), 3.36−3.30 (t, 2H, CHCH2Ph),
1.43 (s, 9H, C(CH3)3) 1.40−1.34 (t, 3H, J = 7.3 Hz, OCH2CH3); 13
C
NMR (100 MHz, CDCl3) δ 173.0, 161.3, 154.9, 147.2, 136.1, 129.3,
128.5, 127.1, 80.2, 61.4, 53.8, 41.5, 28.2, 14.3; HRMS (ESI) m/z calcd.
for C19H24N2NaO4S [M + Na]+ 399.1354, observed 399.1346.
(S)-2-(1-Amino-2-(4-methoxyphenyl)ethyl)thiazole-4-car-
boxylic Acid, 2,2,2-Trifluoroacetate Salt (Phenylalanine Thia-
zole 3). 2.0 g (5.3 mmol) of Boc-protected phenylalanine thiazole 2
was dissolved in methanol (7 mL). To this stirred solution, NaOH (1 N,
12 mL) was added dropwise. The reaction mixture was stirred for
another 1.5 h. After completion of the reaction, the methanol was
evaporated and the aqueous layer was acidified with 5% of aqueous
hydrochloric acid. The aqueous layer was extracted with EtOAc (3 ×
30 mL). The organic layer was washed with brine, dried over Na2SO4
and concentrated under reduced pressure. The gummy free carboxylic
acids was dissolved in dichloromethane (10 mL). To this solution,
trifluoroacetic acid (10 mL) was added at 0 °C and stirred for about
1.5 h. After completion of the reaction, the volatiles were removed
under reduced pressure and the product (free amino acid) was pre-
cipitated using diethyl ether to yield 1.8 g (94%). The free amino acid
was directly used in the next step without purification.
8.02 (s, 3H, CH, thiazole), 7.34−7.29, 7.15−7.13 (m, 15H, 15 × CH
(Phenyl)), 5.76−5.71 (m, 3H, 3 × NHCHCH2), 3.59−3.54 (dd, 3H,
J = 4.6 Hz, CHCH2Ph), 3.13−3.07 (dd, 3H, J = 3.6 Hz, CHCH2Ph);
13C NMR (100 MHz, CDCl3) δ 168.2, 159.4, 148.5, 135.8, 129.7,
128.6, 127.2, 123.9, 52.7, 44.0, 26.8; HRMS (ESI) m/z calcd. for
C36H30N6NaO3S3 [M + Na]+ 713.1439; observed 713.1434.
Cyclization of 5 to Afford Cyclic Tripeptide 6. The same
protocol as described above was used for the synthesis of the tyrosine-
containing cyclic tripeptide 6. 1.96 g (5.0 mmol) of amino acid tri-
fluoroacetate 5 afforded 1.0 g (75%) of 6 as a white solid; mp = 115−
117 °C; UV (λmax) = 228 nm, 251 nm; [α]D20 + 18.42 (c = 1, MeOH);
IR ν (cm−1) 3401, 2924, 1665, 1540, 1511, 1383, 1247, 1178, 1107,
1033, 821, 756; 1H NMR (400 MHz, CDCl3) δ 8.65−8.63 (d, 3H, J =
8.0 Hz, NH, amide), 8.02 (s, 3H, CH(thiazole)), 7.06−7.04 (d, J = 8.8
Hz, 6H, 6 × CH(phenyl)), 6.86−6.83 (d, J = 8.8 Hz, 6H, 6 ×
CH(phenyl)), 5.70−5.65 (m, 3H, 3 × CH, NHCHCH2), 3.80 (s, 9H,
3 × OCH3), 3.53−3.48 (dd, 3H, J = 4.4 Hz, CHCH2), 3.06−3.00 (dd,
3H, J = 4.4 Hz, CHCH2); 13C NMR (125 MHz, CDCl3) δ 168.4,
159.5, 158.8, 148.6, 130.7, 127.8, 123.9, 113.9, 55.2, 52.9, 43.1; HRMS
(ESI) m/z calcd. for C39H36N6NaO6S3 [M + Na]+ 803.1756 observed
803.1754.
Cyclization of Phenylalanine Thiazole 3 to Afford Cyclic
Tripeptide 4. 1.80 g (5.0 mmol) of amino acid trifluoroacetate 3 and
3.34 g (7.5 mmol) of BOPCl were dissolved in DMF (140 mL) and
cooled to 0 °C. To this solution 5.48 g (42.4 mmol) of DIPEA was
added and the reaction mixture was stirred for further 12 h. After
completion of the reaction, the solvent was evaporated under reduced
pressure and diluted with EtOAc (150 mL). The organic layer was
washed with 5% HCl (2 × 50 mL), saturated NaHCO3 solution (3 ×
50 mL), brine (50 mL) and dried over anhydrous Na2SO4. The
organic layer was then concentrated under reduced pressure. The
product was purified by silica gel column chromatography using 60%
EtOAc/petroleum ether as solvent system to afford 0.926 g (78%) of
the pure cyclic tripeptide 4 as a colorless solid, mp = 131−133 °C; UV
X-ray Crystallography. Single crystal X-ray data sets were
collected on a Bruker APEX DUO CCD diffractometer using Mo
Kα radiation (λ = 0.71073 Å) at the desired temperature by using
Oxford Instrument Cryojet-HT controller. The collected data were
reduced by using program SAINT.15 Empirical absorption correction
was carried out by using the program SADABS.16 The crystal system
was determined by Laue symmetry and space groups were assigned on
20
(λmax) = 230 nm; [α]D + 15.63 (c = 1, MeOH); IR ν (cm−1) 3393,
1
2926, 1668, 1538, 1486, 1277, 1123, 1068, 995, 804, 745, 705; H
NMR (400 MHz, CDCl3) δ 8.65−8.63 (d, 3H, J = 8.0 Hz, 3 × NH),
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Figure 1. The crystal structures of thiazole cyclic tripeptides 4 and 6: (A) 4 from methanol, crystal system monoclinic, space group P21; (B) 4 from
toluene, crystal system triclinic, space group P1; (C) 4 from chlorobenzene, crystal system triclinic, space group P1, (D) 4 from ethyl acetate, crystal
system trigonal, space group P32; (E) 6 from toluene, crystal system orthorhombic, space group P212121.
the basis of systematic absences by using XPREP. All the structures were
obtained by direct methods using SHELXS-97.17 Hydrogen atoms were
fixed geometrically and refined isotropically. ORTEP was used for struc-
ture visualization and making the molecular representation. Packing
diagrams were generated by using Mercury.
is trapped in the center above the cyclic ring backbone of the
tripeptide by forming a weak hydrogen bond (2.693 Å) with
the proton of an amide moiety.
All trans amide NHs are pointing inside the ring. Inspection
of the hydrogen bond parameters reveals that there is no intra-
molecular hydrogen bond observed between the NH units or
with the nitrogen of the thiazole ring.11f Examination of the crys-
tal packing reveals that the cyclic peptide adapted a well-organized
supramolecular architecture in the crystal (Figure 2A). A
network of S···O interactions with a distance of 3.03 Å (the
sum of the van der Waals radii of sulfur and oxygen is 3.32 Å)
and S···H interactions determines the self-assembly. The most
important intermolecular S···O distances are compiled in Table 1.
In addition, other interactions such as C−H···π, C−H···O, π···π
and S···π interactions support the supramolecular assem-
bly. Details with respect to these distances are provided in
Supporting Information.
The serendipity of S···O mediated supramolecular assembly
of the tripeptide 4 led us to grow the crystals in toluene,
chlorobenzene, and ethyl acetate to further understand the
molecular behavior and polymorphisms. The crystals of the
cyclic peptide obtained from the solution in toluene revealed a
structure as shown in Figure 1B. Surprisingly, the cyclic peptide
adapted overall a different type of crystal packing compared
to the crystals grown in methanol. The asymmetric unit con-
tains two molecules of the cyclic tripeptide associated with two
molecules of toluene. In contrast to the structure in methanol,
the tripeptide 4 adapted a closed structure exposing the cyclic
backbone for other noncovalent interactions. Two molecules of
4 are connected via toluene through CH···π and C−H···O
RESULTS AND DISCUSSION
■
As a part of our ongoing research to study heterocyclic amino
acid containing cyclic peptide antibiotics and to understand
their molecular architectures and polymorphisms, we synthe-
sized phenylalanine thiazole cyclic peptides. The phenylalanine
thiazole ω-amino acid 3 was prepared according to the reported
procedures.14 Key is the reaction of a bromopyruvate with
thioamide 1 to assemble the thiazole ring. The macrocycliza-
tion of the trifluoroacetate salt of the free amino acid 3 was
mediated by BOPCl in the presence of DIPEA (Scheme 1a).
The thiazole-containing cyclic tripeptide 4 was isolated in good
yield (78%) along with traces of cyclic tetra- and pentapeptides.
1H NMR spectroscopy (in chloroform and in methanol) has
unequivocally indicated the C3-symmetric nature of the molecule.
An analogous procedure afforded the tyrosine-derived thiazole
cyclic tripeptide 6 starting from amino acid trifluoroacetate salt 5
(Scheme 1b).
Because of our interest in the behavior of the side chains, we
tried to get crystals from different solvents. Slow evaporation of
a solution of 4 in methanol yielded crystals with a molecular
structure shown in Figure 1A. The thiazole-containing cyclic
peptide backbone appeared slightly distorted from the planarity
(with rms deviation 0.41, see Supporting Information). As
anticipated all benzyl groups of the cyclic peptide are projecting
at one face of the molecule. Interestingly, the solvent methanol
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Figure 2. Supramolecular assembly of cyclic tripeptide 4 in methanol (A) and in toluene (B). The solvent molecules are highlighted in light blue.
(C) Top view of B showing a network of S···O interactions in the horizontal direction.
Table 1. S···O Interactions Observed in the Crystal Structures of Thiazole Cyclic Tripeptides
crystals from
S···O
d [Å]
S···OC [deg]
crystals from
S···O
d [Å ]
S···OC [deg]
4 (MeOH)
4 (PhMe)
S1···O2
S1···O2
S2···O3
S3···O1
S4···O5
S5···O6
S6···O4
S2···O3
S3···O1
S4···O7
3.039
3.049
3.219
3.213
3.312
3.055
3.130
3.171
3.236
3.189
133
146
143
143
141
145
143
144
141
143
4 (EtOAc)
4 (PhCl)
S5···O8
S1···O2
S2···O3
S3···O1
S4···O4
S5···O6
S6···O5
3.305
3.303
3.249
3.074
3.132
3.064
3.275
140
141
141
146
142
148
141
4 (EtOAc)
O-methyl tyrosine cyclic tripeptide
S2···O6 3.140
6 (toluene)
149
interactions. The corresponding side view is depicted in Figure 2B.
The careful examination of the crystal structure reveals
that the supramolecular architecture is stabilized by the six
C−H···O and the six S···O interactions in the horizontal direc-
tion (Figure 2C). The distances of C−H···OC interactions
lie within the limits of the standard C−H···O distances (2−3 Å),8
whereas the C−H···O angles were found to be in the range
of 108−120°. The carbonyl oxygen is involving in bifurcated
C−H···O and S···O interactions. The distances of six different
S···O interactions from the top and the bottom plane are in the
range of 3.06−3.31 Å (as compiled in Table 1). Similarly, the
crystals grown from a solution of chlorobenzene show an
isomorphic structure (Figure 1C). Furthermore, the crystal pack-
ing is stabilized by six C−H···O and six S···O interactions in the
horizontal planes (top and bottom), and the two tripeptides are
interconnected by chlorobenzene molecules similar to toluene.
The distances and bond angles of S···O interactions are given
in Table 1, and the parameters of the other interactions are
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tabulated in Supporting Information. The Cl(1) is involved in a
bifurcated hydrogen bonding with C(6)−H and C(50)−H with
distances of 2.82 and 2.89 Å and C−H···Cl(1) angles of 152°
and 149°, respectively. Interestingly, Cl(2) is involved in a lone
pair···π interaction with another molecule of chlorobenzene but
not in hydrogen bonding.
Crystals of the peptide obtained from a solution of ethyl
acetate revealed the structure shown in Figure 1D. In contrast
to the structure obtained from the crystals grown in toluene,
the peptide adapted a different packing. The supramolecular
assembly of the cyclic peptide is shown in the Supporting
Information. Interestingly, the phenyl side chains are directly
involved in the C−H···π interaction with phenyl groups of
another cyclic peptide in the crystal packing. In contrast to the
structures from toluene and chlorobenzene, four S···O inter-
actions (Table 1) along with C−H···O interactions are observed
in the horizontal assemblies of both the planes. Instructively, an
average CO···S bond angle of about 143° is observed in all
crystal structures.
To further understand the influence of nonpolar solvents in
the crystallization of tripeptides with the polar head groups,
crystals of the tyrosine-derived cyclic tripeptide 6 were grown
from a solution of toluene yielding the molecular solid state
structure shown in Figure 1E. Instructively, the peptide adapted
a molecular assembly similar to that of 4 obtained from a
solution of methanol (Figure 1A). Only one S···O interaction is
observed with a distance of 3.14 Å and an S···OC bond angle
of 149°. However, in contrast to the peptide crystals grown in
methanol, an interaction of the solvent toluene with the thiazole
ring is observed in the tripeptide 6.
The analysis of the crystal structures from different solvents
suggests the striking influence of the solvent in architecting
divergent supramolecular assemblies. The cyclic peptides may
adopt different molecular conformations based on the polarity
of the molecule and the solvent. However, all these divergent
supramolecular assemblies are predominantly mediated by S···O
interactions. The role of nonbonded intramolecular S···O inter-
actions in organic reactions has been well recognized;9f,i−m how-
ever, very little is known about intermolecular S···O interactions.
To get deeper insights into the supramolecular assemblies
in the solid state and the respective S···O interactions, theo-
retical calculations were performed. The most striking struc-
tural motif is the close contact between a peptidic carbonyl on
the one hand side and the sulfur and the hydrogen of the
thiazole ring on the other (as depicted in Figure 2C). Therefore,
two model systems 7 and 8 consisting of thiazole and acetyl-
N-methylamide were investigated (Figure 3) by means of the
systems shown in Figure 3 all the geometrical parameters were
optimized with Gaussian0320 using the counterpoise procedure
to obtain a BSSE-corrected supramolecular assembly. Energies
were corrected for zero-point and the corresponding geom-
etries were characterized as minima by subsequent frequency
calculation. Our investigations revealed several minima, a global
one with a skewed arrangement being 20.4 kJ/mol more stable
than the separate monomers (see Supporting Information) and
the two local ones showing a very similar geometry as observed
in the solid-state architecture. The local ones in which the two
molecules are almost located in one plane are about 16.0 kJ/mol
(7) and 16.6 kJ/mol (8) more stable than separated thiazole and
acetyl-N-methylamide. We assume that most of the interaction
energy is attributed to dispersion forces; corresponding natural
bond orbital (NBO) analyses21 having been performed on the
dimer’s optimized geometry did not result in a clear-cut charge
transfer from one functionality to another.
CONCLUSION
■
In summary, phenylalanine- and tyrosine-derived thiazole-con-
taining cyclic tripeptides 4 and 6 were synthesized by BOPCl/
DIPEA-mediated trimerization of the corresponding amino
acids. X-ray investigations performed with crystals obtained
from various solvents (methanol, toluene, chlorobenzene, and
ethyl acetate) revealed strongly divergent supramolecular
assemblies in the solid state. All of them are predominantly
mediated by nonbonded intermolecular S···O interactions of a
thiazole and a carbonyl unit arranged in a coplanar fashion.
Theoretical calculations at the MP2 level of theory using
appropriate model systems have shown that a significant energy
gain of about 16 kJ/mol is associated with such an arrangement.
Thus, interactions with thiazole as the crucial structural element
might also play an important role for the biological activity
of thiazole-containing cyclic peptide antibiotics and may offer
new opportunities for the construction of novel supramolecular
assemblies and materials.
ASSOCIATED CONTENT
■
S
* Supporting Information
1
X-ray structure analyses, H and 13C NMR spectra, Gaussian
Archive Entries, ORTEP diagrams of peptide structures and
noncovalent interactions data. Further crystallographic infor-
mation can be obtained from The Cambridge Crystallographic
Data Centre (CCDC) Nos. 807926-807928, 904832 and 904833.
This material is available free of charge via Internet at http://pubs.
acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: hn.gopi@iiserpune.ac.in (H.N.G.); dwerz@gwdg.de
(D.B.W.).
Notes
Figure 3. Simplified predominant motifs 7 and 8 in the solid-state
structure of the cyclic thiazoles resulting in an interaction energy of
16.0 kJ/mol (7) and 16.6 kJ/mol (8), respectively.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
MP2/6-311G++(3df,3dp) level of theory.18,19 Previous studies
revealed that such a level of theory provides a very efficient way
for estimating coupled cluster interaction energies, whereas the
B3LYP method leads to quite good geometries but is incapable
of recovering correct interactions energies.9h,e For the model
This work was supported by the Department of Science
Technology, Govt. of India. S. M. M., A. B., and S. V. J are
thankful to CSIR for research fellowships. D.B.W. thanks the
German Research Foundation (DFG) and the Fonds der
Chemischen Industrie for generous support of his work.
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