A theoretical study of the conformational preference of alkyl- and aryl-substituted pyrogallol[4]arenes and evidence of the accumulation of negative electrostatic potential within

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A theoretical study of the conformational preferenceof alkyl- and aryl-substituted pyrogallol[4]arenes andevidence of the accumulation of negative electrostaticpotential within the cavity of their rccc conformersSebastiaacuten Manzanoab Cesar H Zambranoab Miguel Angel Mendezab Eric E Duenoc RobertA Cazarbd amp F Javier Torresab

a Grupo de Quiacutemica Computacional y Teoacuterica (QCT-USFQ) Universidad San Francisco deQuito Diego de Robles y Viacutea Interoceaacutenica 17-1200-841 Quito Ecuadorb Grupo Ecuatoriano para el Estudio Experimental y Teoacuterico de Nanosistemas ndash GETNano ndashUniversidad San Francisco de Quito Edificio Newton Oficina N102C Quito Ecuadorc Division of Arts and Sciences Bainbridge College Bainbridge GA39818 USAd Facultad de Ciencias Escuela Superior Politeacutecnica de ChimborazoPanamericana Sur Km15 Riobamba EcuadorPublished online 16 Jul 2013

To cite this article Sebastiaacuten Manzano Cesar H Zambrano Miguel Angel Mendez Eric E Dueno Robert A Cazar amp FJavier Torres (2014) A theoretical study of the conformational preference of alkyl- and aryl-substituted pyrogallol[4]arenesand evidence of the accumulation of negative electrostatic potential within the cavity of their rccc conformers MolecularSimulation 404 327-334 DOI 101080089270222013806806

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A theoretical study of the conformational preference of alkyl- and aryl-substitutedpyrogallol[4]arenes and evidence of the accumulation of negative electrostaticpotential within the cavity of their rccc conformers

Sebastian Manzanoab Cesar H Zambranoab Miguel Angel Mendezab Eric E Duenoc Robert A Cazarbd

and F Javier TorresabaGrupo de Quımica Computacional y Teorica (QCT-USFQ) Universidad San Francisco de Quito Diego de Robles y Vıa Interoceanica17-1200-841 Quito Ecuador bGrupo Ecuatoriano para el Estudio Experimental y Teorico de Nanosistemas ndash GETNano ndash UniversidadSan Francisco de Quito Edificio Newton Oficina N102C Quito Ecuador cDivision of Arts and Sciences Bainbridge CollegeBainbridge GA 39818 USA dFacultad de Ciencias Escuela Superior Politecnica de ChimborazoPanamericana SurKm 15 Riobamba Ecuador

(Received 18 March 2013 final version received 15 May 2013)

We report a theoretical study of the structural and electronic properties of the rccc and rctt conformers of severalpyrogallol[4]arenes R-Pyg[4]arenes (ie R frac14 fluoroethyl methyl t-butyl phenyl tolyl and p-fluorophenyl) carried out byemploying the HF-DFT hybrid B3LYP functional Comparison of the B3LYP energies of the two stereoisomers showed thatthe rccc conformer is more stable than its rctt counterpart for all the derivatives considered However calculations made withthe double-hybrid Grimmersquos B97D functional confirmed the experimental observation that the relative stability depends onthe type of the R substituents These results clearly suggest that the B97D functional together with large enough basis sets(ie split-valence plus polarisation and diffuse functions) is sufficiently accurate for the purpose of describing theconformational features of these compounds Computed electrostatic potential maps of the rccc of the differentR-Pyg[4]arenes showed that a negative potential is present within the cavity of these compounds In addition it is observedthat the size of this negative electrostatic potential depends on the electron-donating or electron-withdrawing character of theR substituents

Keywords macromolecules pyrogallol DFT conformational preference electrostatic potential

1 Introduction

In the last few decades there has been an increased interest

in the potential applications of compounds generally

denoted as calixarenes carcerands and cavitands[12]

Pyrogallol[4]arenes (referred to as R-Pyg[4]arenes here-

after) which are macromolecular cyclic oligomers that

belong to the group of compounds mentioned earlier[3]

have been the object of intensive research due to their

interesting features which include solution behaviour

structural simplicity selectivity recognition and the

presence of a variety of conformational preferences[4ndash8]

These unique characteristics make these macromolecules

as interesting candidates for a number of applications such

as pharmaceutical drug carriers nano-sensors and gas--

storage devices[9ndash12]

An important structural feature of R-Pyg[4]arenes is

the relative orientation of the R substituents (ie up or

down) with respect to the mean macrocyclic plane This

feature results in the formation of various stereoisomers

among which the most common are the cup-like (rccc) and

the chair-like (rctt) conformers (see Scheme 1)[1]

Concerning the stereoisomerism of these compounds

there is a plethora of experimental evidence indicating that

the conformation of pyrogallol[4]arenes synthesised by

means of the acid-catalysed condensation of pyrogallol

units (C6(OH)3H3) with aldehydes (R-CHO) depends

exclusively on the aldehydersquos R group[113ndash15] More

precisely it has been observed that aliphatic aldehydes lead

to the formation of rccc isomers whereas aromatic

aldehydes produce macrocycles with rctt structure[16]

Only recently Maerz et al [17] were able to produce an

aromatic-substituted rccc conformer although induced by

the presence of Zn2thorn ions This remarkable report not only

demonstrates that cup-like structures are possible for

aromatic-substituted pyrogallol[4]arenes but also shows

that conformational and size control can be attained for

these compounds allowing them to be classified as

important structure-tunable macromolecules

Despite the interesting properties of pyrogallol[4]ar-

enes only few theoretical studies of their properties have

been reported Maerz et al [17] and Rozhenko et al [18]

have investigated the conformational features of phenyl-

and methyl-substituted pyrogallol[4]arenes respectively

by means of DFT and post-HartreendashFock MP2 calcu-

lations These studies showed in agreement with the

experimental evidence that the rccc conformation is the

q 2013 Taylor amp Francis

Corresponding author Email jtorresusfqeduec

Molecular Simulation 2014

Vol 40 No 4 327ndash334 httpdxdoiorg101080089270222013806806

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most stable one for the alkyl-substituted compound

whereas the rctt conformation is the preferred one for the

aryl-substituted macromolecule However the effect of

other alkyl- or aryl-substituent groups on the conformation-

al preference of pyrogallol[4]arenes has not been addressed

by these authors More recently Fraschetti et al[19]

reporting on an experimental study of the enantioselectivity

of rccc-281420-tetra-n-decyl-4101622-tetra-O--

methylresorcin[4]arene have suggested that the structural

features as well as the sorption properties of this specific

system can be accurately reproduced by the Grimmersquos

B97D functional [20] because this functional includes

dispersive forces which as indicated by Novikov and

Shapiro[21] appear to be essential for determining the

properties of cavitands

In contrast with the few theoretical studies published

on the properties of pyrogallol[4]arenes an important

number of theoretical reports are available in the case of

their parent compounds calix[n]arenes These are

macrocyclic molecules consisting of four five or six

phenol rings connected via methylene bridges located at an

ortho position with respect to the hydroxyl groups (see

Scheme 2)[122] Considering the close relation between

these compounds and pyrogallol[4]arenes some of the

results on their conformational features obtained at

different levels of theory are summarised in the following

Previous theoretical studies on calix[n]arenes relied

because of their low computational cost on semi-empirical

methods[23ndash32] It can be emphasised that MM2 MM2P

AMBER and CHARMm force fields correctly reproduce

the relative stability of substituted calix[4]arenes [2326]

nonetheless results obtained from these methods showed

pronounced quantitative differences caused by the

different potentials employed for describing electrostatic

forces which are the main (but not the unique) interactions

in calix[4]arenes[1323] In Refs [2425] Harada et al

showed that the MM3 force field is superior than those

mentioned earlier as the p-aromatic system is also taken

into account for the description of the calix[4]arenes

conformers The latter studies suggested that the relative

stability of substituted calix[4]arenes conformers is a result

of a combined effect between electrostatic forces caused by

steric effects and intra-molecular hydrogen bonding More

precisely Harada et al [25] concluded that the cup-like

conformation is the most stable one when hydrogen bonds

can be formed at the lower rim of substituted calix[4]ar-

enes However as concluded by Aleman and Casanovas

[31] rotational isomerism (ie rccc to rctt or rtct transition)

is possible only when -OH groups of the lower rim are

replaced by methoxy groups Finally Bernardino et al [29]

indicated that although the semi-empirical AM1 method

accurately predicts the structure of p-tertbutyldihomoox-

acalix[4]arene higher level calculations (ie post-Har-

treendashFock or DFT) are needed to obtain bond dissociation

energies in agreement with experimental data which will

allow a correct description of the pathways of calix[4]arene

conformational interconversion[2631] Regarding the

DFT studies on calix[4]arenes it can be pointed out that

structural results based on these methods corroborate

previous results obtained with semi-empirical approaches

For instance the studies carried out at the B3LYP level of

Scheme 1 Schematic representation of rccc (a) and rctt (b) conformations of R-Pyg[4]arenes For the sake of clarity the OH groups ofpyrogallol units are omitted

Scheme 2 Schematic representation of R-substitutedcalix[4]arenes

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Novikov et al[33] Kim and Choe [34] and Kim et al [35]

support the fact that the great stability of the cup-like

conformer over the other possible structures can be

attributed to the formation of intra-molecular hydrogen

bonds which contributes with about 100 kJmol to the total

energy of the rccc conformer as estimated using the

procedure proposed by Grootenhuis et al [23]

In this study a computational study of different

derivatives of pyrogallol[4]arenes in the gas phase with

rccc and rctt conformations is carried out In the first part

of this study we use the B3LYP functional [36] to describe

the structure of the different rccc and rctt derivatives In

this way we may compare our results with those reported

by Maerz et al [17] and others for related calix[n]arenes

compounds[33ndash35] In addition acknowledging the work

of Fraschetti et al[19] the B97D functional is also

employed to obtain a more accurate description of the

conformational features of pyrogallol[4]arenes[21]

Finally based on these calculations we analysed the

localisation of negatively charged regions in R-substituted

pyrogallol[4]arenes by examining computed electrostatic

potential maps Our main interest at this stage was to

determine the extent to which a negative region

accumulates in the R-substituted pyrogallol[4]arene cavity

and to ascertain how this accumulation was affected by the

presence of electron-donating and electron-withdrawing

character of the R-substituent groups

2 Models and methods

The gas-phase molecular model of the rccc conformer of

decyl-Pyg[4]arene obtained by cutting out a single

molecule from its corresponding crystal structure reported

by Dueno et al[37] was employed as a starting point The

rcccmodels of the R-Pyg[4]arenes considered in this study

were constructed by substituting the decyl groups for

fluoroethyl methyl t-butyl phenyl tolyl or p-fluorophenyl

groups The same procedure was employed to construct the

models of the rctt conformers although the structure of

phenyl-Pyg[4]arene also obtained from available X-ray

diffraction data [38] was employed as a starting point1 In

the first stage of the study the models of the rccc and rctt

conformers of the different R-Pyg[4]arenes were fully

optimised with the program Gaussian09 [39] by adopting

the B3LYP and the B97D functionals as levels of theory

together with two basis sets of increasing size namely

6-311G(dp) and 6-311thornthornG(dp) It is important to point

out that although the use of the 6-311Gthornthorn(dp) basis sets

for the quantum-mechanical simulation of large systems

such as R-Pyg[4]arenes represents a demanding compu-

tational task basis sets including diffuse functions are

considered in this study to retrieve some of the electron

correlation in the description of these macrocycles To save

the computational resources symmetry constrains were

imposed for the optimisation process by considering that

all rccc and rctt molecules belong to the C4 and Ci point

groups respectively2

Upon obtaining the computed equilibrium geometries

vibrational frequencies were calculated at both B3LYP6-

311G(dp) and B97D6-311G(dp) levels of theory within

the harmonic approximation and using first and second

analytical derivatives for the construction of the Hessian

matrix The analysis of the resulting Hessian matrix

confirmed that all rccc-C4 and rctt-Ci structures corre-

spond to global minima in the potential energy surface

rccc versus rctt relative stability was determined through

single point energy calculations performed at the

B3LYP6-311G(dp) B3LYP6-311Gthornthorn(dp) B97D6-

31G(dp) level and at the B97D6-311thornthornG(dp) levels by

employing a tighter convergence criterion for the SCF

procedure (ie 10210 on the root mean square of the

elements of the density matrix) This strategy was adopted

to obtain well-converged wave functions for further

analysis of the electronic properties Electrostatic potential

cubes were generated from the resulting wave functions by

means of the cubegen utility [39] of Gaussian09 adopting a

coarse grid Finally electrostatic potential maps were

plotted with GaussView5[40]

Table 1 Relative stability of the various R-Pyg[4]arenes stereoisomers computed as DE frac14 Erctt2Ercccat the B3LYP6-311G(dp)

B3LYP6-311 thorn thorn G(dp) B97D6-311G(dp) and B97D6-311 thorn thorn G(dp) levels of theory

DE B3LYP6-311G(dp) DEB3LYP6-311thornthornG(dp) DE B97D6-311G(dp) DE B97D6-311thornthornG(dp)

R-Pyg[4]arene (kJmol) (kJmol) (kJmol) (kJmol)

R frac14 alkylFluoroethyl-Pyg[4]arene 849 759 622 540Methyl-Pyg[4]arene 682 568 488 382t-Butyl-Pyg[4]arene 1072 1015 489 499R frac14 arylPhenyl-Pyg[4]arene 143 45 276 290Tolyl-Pyg[4]arene 155 61 296 2115p-Fluorophenyl-Pyg[4]arene 149 45 2131 2126

Note Values are reported in kJmol

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3 Results and discussion

31 Relative stability of the rccc and rctt

R-Pyg[4]arenes

A comparison of the B3LYP6-311G(dp) energies of the

conformers (ie DEB3LYP6-311G(dp) frac14 Erctt 2 Erccc) for the

different R-Pyg[4]arenes is reported in Table 1 in which it

is shown that the rccc conformation is the most stable

structure regardless of the R group present in all the

macromolecules under investigation Although this clearly

contrasts with many experimental observations on the

conformational preference of pyrogallol[4]arenes[41]

further analysis of the computed data indicates a substantial

difference between the DEB3LYP6-311G(dp) values obtained

for the alkyl- and the aryl-substituted compounds In the

case of the alkyl-substituted systems the energy difference

of the conformers is significantly large ranging from

682 kJmol to 1072 kJmol The DEB3LYP6-311G(dp) values

computed for the aryl-substitutedmolecules are smaller and

close to 150 kJmol This difference in the computed

values suggests that from a theoretical point of view it is

possible to produce aryl-Pyg[4]arenes with the rccc

conformation[17] but alkyl-Pyg[4]arenes with rctt confor-

mation are more difficult to produce due to a thermodyn-

amic impediment The same observation can be made from

the energy difference computed at B3LYP6-311thornthornG(d

p) In Table 1 it is reported that the average value of

DEB3LYP6-311thornthornG(dp) decreases from 150 kJmol to

45 kJmol for the case of aryl-Pyg[4]arenes whereas

DEB3LYP6-311thornthornG(dp) values of alkyl-Pyg[4]arenes remain

as large differences of stability ranging from 568 kJmol to

1015 kJmol This evidence suggests that the inclusion of

diffuse functions in the basis set somehow stabilises the rctt

conformer indicating that dispersion forces are expected to

be relevant in determining the conformational stability in

R-Pyg[4]arenes

In addition to these observations it is important to point

out the fact that all the DEB3LYP6-311G(dp) are positive that

can be explained by considering two aspects (i) as the

number of atoms and interatomic bonds are the same in both

the rccc and rcttR-Pyg[4]arenes the relative stability of the

conformers is solely determined by the strong Hmiddot middot middotOH and

the weak Hmiddot middot middotp and pmiddot middot middotp interactions [42] in which p

interactions are due to the electronic clouds of the benzene

groups and (ii) the well-known fact that traditional DFT

functionals are not considered capable of describing

dispersive forces which in the present systems are

responsible for the weak interactions[43] Considering the

statements mentioned earlier it can be suggested that the

most stable conformer at the B3LYP6-311G(dp) and

B3LYP6-311thornthornG(dp) levels corresponds to the struc-

ture that exhibits an arrangementwith the greater number of

strong Hmiddot middot middotOH bonds This can be illustrated by inspecting

the optimised structure of the rccc and rctt conformers of

t-butyl-Pyg[4]arene (ie the system with the largest

DEB3LYP value as reported in Table 1) depicted in Figure

1 In the case of the rccc structure the upper rim is formed

by the 12 hydroxyl groups that belong to the four pyrogallol

units of the macrocycle These groups are oriented in the

same direction (ie clockwise) resulting in the maximisa-

tion of the number of both intra- and inter-pyrogallol

Hmiddot middot middotOH bonds As indicated in Figure 1(a) distances of

211 and 212 A were computed for the intra-pyrogallol

H1middot middot middotO2H2 and H2middot middot middotO3H3 bonds whereas a value of

185 A was obtained for the inter-pyrogallol H3middot middot middotO1H1

bond suggesting that the latter interaction is stronger than

the former interactions (see the inset in Figure 1(a) for

atomic labels) In the rctt conformation of the t-butyl-Py-

g[4]arene the situation is different the 12 hydroxyl groups

of the macrocycle are separated into two sets of six axial

groups (ie O1H1 O2H2 and O3H3 plus symmetry

equivalents) and six equatorial groups (ie O4H4 O5H5

Figure 1 (Colour online) B3LYP6-311G(dp) optimised structures of rccc (a) and rctt (b) t-butyl-Pyg[4]arene The Hmiddot middot middotOH stronginteractions present in both isomers are represented with red dashed lines Symmetry irreducible OH groups are labelled Carbon oxygenand hydrogen atoms are represented with grey red and white colours respectively For the sake of clarity t-butyl groups are representedwith the large blue spheres

S Manzano et al330

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and O6H6 plus symmetry equivalents) which in contrast to

the rccc conformation are capable of forming only

intra-pyrogallol Hmiddot middot middotOH bonds of lengths ranging from

213 to 215 A and not the stronger inter-pyrogallol Hmiddot middot middotOH

bonds (see Figure 1(b)) By considering this structural

description of the t-butyl-Pyg[4]arene conformers it seems

reasonable to point out that the extra stabilisation of the rccc

molecule (ie DEB3LYP6-311G(dp) frac14 1072 kJmol

DEB3LYP6-311thornthornG(dp) frac14 1015 kJmol) (Table 1) is primar-

ily due to the four inter-pyrogallol Hmiddot middot middotOH bonds which

are present in the rccc isomer but not in its rctt counterpart

The same results were observed for the other R-Pyg[4]ar-

enes studied ofwhich the optimised structures are shown in

Figures S1ndashS5 (Supplementary material available via the

article webpage)

The results described above allow us to conclude that

the analysis of the alkyl- and aryl-substituted pyrogallo-

l[4]arenes carried out at the B3LYP6-311G(dp) and

B3LYP6-311thornthorn G(dp) levels of theory is not accurate

enough Therefore it is clear that alternative methods

Figure 2 (Colour online) Total charge and negative electrostatic potential maps of (top) methyl-Pyg[4]arene and (bottom) fluoroethyl-Pyg[4]arene plotted from their corresponding wave functions computed at the B97D6-311G(dp) level of theory The maps were plottedwith an isosurface value of 003 ebhor3 Carbon oxygen and hydrogen atoms are represented with grey red and white coloursrespectively

Molecular Simulation 331

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capable of describing the weak Hmiddot middot middotp and pmiddot middot middotp

dispersive interactions[44] are necessary for an adequate

study of the structural properties of these macromolecules

In an effort to include the dispersive forces in the present

theoretical description of the various R-Pyg[4]arenes and

acknowledging the work of Fraschetti et al[19] the

double-hybrid Grimmersquos B97D functional was also

employed to investigate the structural properties of the

various R-Pyg[4]arenes The B97D functional contains a

dispersion correction term [20] capable of estimating the

weak Hmiddot middot middotp and pmiddot middot middotp interactions that are present in the

rctt conformers of the aryl-substituted pyrogallol[4]arenes

and might therefore result in a change in the relative

stability of the conformers As reported in Table 1 the

energy difference between the rctt and rccc conformers of

the R-Pyg[4]arenes obtained at both B97D6-311G(dp)

and B97D6-311thornthornG(dp) levels decreases significantly

in comparison with the values obtained at the

B3LYP6-311G(dp) and B3LYP6-311thornthornG(dp) levels

respectively As a result a difference in the conformational

preference of the alkyl- and the aryl-substituted pyrogal-

lol[4]arenes is obtained In the case of the latter

compounds the rctt structure represents the most stable

conformer with DEB97D values ranging from 276 kJmol

to2131 kJmol for the B97D6-311G(dp) level and from

290 kJmol to 2126 kJmol for the

B97D6-311thornthornG(dp) level in agreement with the

experimental observations on the conformational prefer-

ence of R subsituted Pyg[4]arenes[1641]

32 Electrostatic potential of rccc R-Pyg[4]arenes

Because the rccc isomer is the most interesting structure

from the point of view of its potential applications and

because it can be produced for both alkyl- and aryl-

substituted pyrogallol[4]arenes as reported by Maerz

et al[17] only this conformer of the various R-Pyg[4]arenes

was considered for the analysis of the electrostatic potential

The electrostatic potential map of methyl-Pyg[4]arene is

shown in Figure 2(a) A salient feature of this map is the

presence of a localised negatively charged region within the

cavity of the cup-like molecule as inferred by plotting only

the negative isovalue of the charge density (see Figure 2(b))

We may conjecture that the origin of this particular

accumulation of negative electrostatic potential inside the

cavity is due to the electron-donating character of themethyl

groups as well as the macromoleculersquos ability to freely

transport charge from the bottom towards the cup and vice

versa as a result of the highlyp-conjugated systempresent in

its structure[45] With the purpose of determining whether

the above inferences hold we also obtained a total charge

density map for the rccc fluoroethyl-Pyg[4]arene for which

the fluoride atoms have a high electron-withdrawing

character The resulting map is shown in Figure 2(c) in

which it is observed that in contrast with the rccc

methyl-Pyg[4]arene negative potential does not accumulate

within the cavityof the compound but is rather located on the

very electronegative F atoms at the bottom of the

macromolecule (see Figure 2(d)) By considering that the

presence or absence of a localised negatively charged region

inside the cavityofR-Pyg[4]arenes depends on theR groups

it is reasonable to suggest that the more electron-donating

character of the R groups the bigger the size of the

negative potential will be within its cavity This can be

confirmed by inspecting the total charge and negative

isovalue electrostatic potential maps of t-butyl-Pyg[4]ar-

ene (see Figure S6 Supplemetary material) in which it is

observed that the negative potential inside this molecule is

in fact bigger than that of methyl-Pyg[4]arene We

observed the same kind of behaviour for the electrostatic

potential maps of the aryl-substituted pyrogallol[4]arenes

investigated In the case of p-fluorophenyl-Pyg[4]arene it

is observed that negative potential does not accumulate

within its cavity due to the presence of the electronegative

F atoms in the R groups However negative potential

accumulates in the interior of the phenyl-Pyg[4]arene and

tolyl-Pyg[4]arene macromolecules where the negative

potential of the latter appears to be the largest one (see

Figures S7ndashS9 Supplementary material available via the

article webpage)

In view of the results mentioned earlier it is reasonable

to suggest that the presence (or absence) of a localised

negatively charged region has an important effect on the

absorption properties of R-Pyg[4]arenes More precisely

it is expected that the presence of a negatively charged

region within the cavity of R-Pyg[4]arenes can favour the

encapsulation of positively charged species In order to

confirm the validity of this conjecture an NH4thorn cation was

added in the interior of the methyl- and fluoroethyl-

substituted pyrogallol[4]arenes of which the cavity

provides an ideal adsorption environment for the nearly

spherical ammonium group (see Figure 3) Upon obtaining

the equilibrium geometries of both NH4thorn-

methyl-Pyg[4]arene and NH4thornfluoroethyl-Pyg[4]arene

complexes BSSE-corrected binding energies (BEc) were

computed for the two complexes at the B97D6-

311G(dp) Values of thorn2298 kJmol and thorn1990 kJmol

were obtained for the NH4thornmethyl-Pyg[4]arene and the

NH4thornfluoroethyl-Pyg[4]arene complexes respectively

These results indicate that although the ammonium

group is strongly bound to the two host macromolecules

a more favourable host ndash guest interaction (ie

DBEc frac14 BEcNH4thornmethyl-Pyg[4]arene ndash BEc

NH4thornfluoroethyl-

Pyg[4]arene frac14 308 kJmol) is present in the NH4thornmethyl-

Pyg[4]arene complex due to the presence of the negative

potential in the cavity of methyl-Pyg[4]arene This

relevant result indicates that the adsorption properties of

R-Pyg[4]arenes might be controlled by the a priori

selection of the R-substituent group

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4 Conclusions

The present theoretical study showed that the B3LYP

functional together with appropriate basis sets predicts

that the rccc conformation of the various R-Pyg[4]arenes

investigated is the most stable structure regardless of the

R-substituent group However results refined at both the

B97D6-311G(dp) and the B97D6-311thornthornG(dp) levels

showed that the B97D functional reproduces the

experimental observations concerning the conformational

preference of alkyl- and aryl-substituted pyrogallol[4]ar-

enes The reason may be clearly ascribed to the fact that

the B97D functional is well suited to cope with the

dispersive forces present in these macromolecules

However it is important to comment that although

structural results obtained at the B97D level agree with a

large number of experimental studies the relatively small

negative energy difference obtained between the two

conformers (ie DEB97D6-311G(dp) 2100 kJmol for

aryl-substituted pyrogallol[4]arenes) suggests that the

theoretical description of these macromolecules could be

improved This might be achieved for instance through

the use of both post HartreendashFock methods and more

flexible basis sets (eg correlation consistent Dunningrsquos

basis sets) for the atoms involved in the weak Hmiddot middot middotp and

pmiddot middot middotp interactions

Concerning the electronic properties the analysis of

total charge and negative electrostatic potential maps of

the various rccc R-Pyg[4]arenes indicates that the interior

cavity of these macromolecules can be filled with negative

electrostatic potential or depleted of it just by varying the

R substituents at the lower rim of the structure It is

important to point out that this observation might open

new possibilities with respect to the applications (ie

adsorption of charged species) of these important

compounds because electronic tuning of the cavity

interior appears feasible by varying the R-substituent

groups

Acknowledgements

This work has made use of the High Performance ComputingSystem of the Universidad San Francisco de Quito (HPC-USFQ)The present project was carried out with funding fromCorporacion Ecuatoriana para el Desarrollo del InternetAvanzado (CEDIA) in the framework of the CEPRA grantsFJT MAM and CZ thank USFQrsquos Chancellor Grantsprogramme (2009 2010 and 2011) for partially financing thisproject FJT also thanks Prof R Sierra at the University ofArizona for granting access to the UofArsquos High PerformanceComputer System where part of this work was performed

Notes

1 Crystallographic information files (iecif files) of the decyl-Pyg[4]arene and phenyl-Pyg[4]arene crystal structures werevisualised and manipulated to obtain the desired molecularmodels with the program MOLDRAW[46]

2 The initial structures of the different R-Pyg[4]arenes (ieRfrac14fluoroethyl methyl t-butyl phenyl tolyl and p-fluorophenyl) were refined with the program GaussView5to obtain models of the rccc and rctt conformers with C4 andCi symmetry respectively[40]

References

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[2] Cram DJ Cram JM Container molecules and their guestsCambridge The Royal Society of Chemistry 1997

[3] Amaya T Rebek J Hydrogen-bonded encapsulation complexes inprotic solvents J Am Chem Soc 200412614149ndash14156

[4] Avram L Cohen Y Self-recognition structure stability and guestaffinity of pyrogallol[4]arene and resorcin[4]arene capsules insolution J Am Chem Soc 200412611556ndash11563

[5] Botta B Delle Monache G Zappia G Misiti D Baratto MC PogniR Gacs-Baitz E Botta M Corelli F Manetti F Tafi A Synthesisand interaction with copper(II) cations of cyano- and aminor-esorcin[4]arenes J Org Chem 2002671178ndash1183

[6] Cave GWV Ferrarelli MC Atwood JL Nano-dimensions for thepyrogallol[4] arene cavity Chem Commun 2005222787ndash2789

[7] Fox OD Leung JF-Y Hunter JM Dalley NK Harrison RG Metal-assembled cobalt(II) resorc[4]arene-based cage molecules thatreversibly capture organic molecules from water and act as NMRshift reagents Inorg Chem 200039783ndash790

[8] Redshaw C Coordination chemistry of the larger calixarenes CoordChem Rev 200324445ndash70

[9] Atwood JL Barbour LJ Jerga A Hydrogen-bonded molecularcapsules are stable in polar media Chem Commun 2001222376ndash2377

[10] Biavardi E Favazza M Motta A Fragala IL Massera C Prodi LMontalti M Melegari M Condorelli GG Dalcanale E Molecularrecognition on a cavitand-functionalized silicon surface J AmChem Soc 20091317447ndash7455

[11] Rebek J Jr Reversible encapsulation and its consequences insolution Acc Chem Res 199932278ndash286

[12] De Zorzi R Guidolin N Randaccio L Purrello R Geremia SNanoporous crystals of calixareneporphyrin supramolecular

Figure 3 (Colour online) Optimised structure of NH4thornmethyl-

Pyg[4]arene complex obtained at B97D6-311G(dp) level oftheory The blue sphere represents the NH4

thorn cation whereas theyellow sphere represents the methyl substituent

Molecular Simulation 333

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complex functionalized by diffusion and coordination of metal ionsJ Am Chem Soc 20091312487ndash2489

[13] Gutsche CD Calixarenes Acc Chem Res 198316161ndash170[14] Han J Song X Liu L Yan C Synthesis crystal structure and

configuration of acetylated aryl Pyrogallol[4]arenes J InclusionPhenom Macrocyclic Chem 200759257ndash263

[15] Weilnet F Schneider H Mechanisms of macrocycle genesis Thecondensation of resorcinol with aldehydes J Org Chem1990565527ndash5535

[16] Morikawa O Iyama E Oikawa T Kobayashi K Konishi HConformational properties of C-2v-symmetrical resorcin[4]arenetetraethers J Phys Org Chem 200619214ndash218

[17] Maerz AK Thomas HM Power NP Deakyne CA Atwood JLDimeric nanocapsule induces conformational change ChemCommun 2010461235ndash1237

[18] Rozhenko A Scheller W Letzel M Decker B Agena C Mattay JConformational features of calix[4]arenes with alkali metal cationsA quantum chemical investigation with density functional theoryTHEOCHEM 20057327ndash20

[19] Fraschetti C Letzel MC Paletta M Mattay J Speranza M FilippiA Aschi M Rozhenko AB Cyclochiral resorcin[4]arenes aseffective enantioselectors in the gas phase J Mass Spectrom20124772ndash79

[20] Grimme S Semiempirical GGA-type density functional constructedwith a long-range dispersion correction J Comput Chem2006271787ndash1799

[21] Novikov AN Shapiro YE Energy and geometry of cooperativehydrogen bonds in p-susbtituted calix[n]- and thiacalix[n]arenes aquantum-chemical approach J Phys Chem A 2012116546ndash559

[22] Gutsche CD Calixarenes Cambridge Royal Society of Chemistry1989

[23] Grootenhuis PDJ Kollman PA Groenen LC Reinhouldt DN vanHummel GJ Ugozzoli F Computational study of the structuralenergetical and acidndashbase properties of calix[4]arenes J Am ChemSoc 19901124165ndash4176

[24] Harada T Rudzinski JM Osawa E Shinkai S Computationalstudies of calix[4]arene homologs influence of 5111723- and25262728-substituents on the relative stability of four conformersTetrahedron 1993495941ndash5954

[25] Harada T Ohseto F Shinkai S Combined NMR spectroscopy andmolecular mechanics studies of OH-depleted calix[4]arenes on theinfluence of OH groups on the relative stability of calix[4]areneconformers Tetrahedron 19945013377ndash13394

[26] Fischer S Grootenhuis PDJ Groenen LC van Hoorn WP vanVeggel FCJM Reinhouldt DN Karplus M Pathways to confroma-tional interconversion of calix[4]arenes J Am Chem Soc19951171611ndash1620

[27] Botta B Delle Monache G De Rosa MC Seri C Gacs-Baitz ESantini A Misiti D Synthesis of C-alkylcalix[4]arenes 5 Designsynthesis computational studies and homodimerization of poly-methylene-bridged resorc[4]arenes J Org Chem 199762932ndash938

[28] Brouyere E Persoons A Bredas JL Geometric structure andsecond-order nonlienar optical response of substituted calix[4]arenemolecules a theoretical study J Phys Chem A 19971014142ndash4148

[29] Bernardino RJ Costa Cabral BJ Pereira JLC Hydrogen bondingand conformational equilibrium in p-tert-butyldihomooxacalix[4]-arene THEOCHEM 199845523ndash32

[30] Ghoufi A Morel JP Morel-Desrosiers N Malfreyt P MDsimulations of the binding of alchohols and diols by a calixarenein water connections between microscopic and macroscopicproperties J Phys Chem B 200510923579ndash23587

[31] Aleman C Casanovas J Theoretical investigation on the rotationalisomerism of calix[4]arenes influence of the hydroxyl-methoxyreplacement J Phys Chem A 20051098049ndash8054

[32] Boulet B Joubert L Cote G Bouvier-Capely C Cossonnet CAdamo C A combined experimental and theoretical study on theconformational behavior of a calix[6]arene J Phys Chem A20061105782ndash5791

[33] Novikov AN Bacherikov VA Shapiro YE Gren AI Ab initio anddensity functional theory studies of cooperative hydrogen bond inacalix[4]- and calix[6]arenes J Struct Chem 2006471003ndash1015

[34] Kim K Choe J DFT conformational study of calix[6]arenehydrogen bond Bull Korean Chem Soc 200930837ndash845

[35] Kim K Park SJ Choe J DFT confromational study of calix[5]areneand calix[4]arene hydrogen bond Bull Korean Chem Soc2008291893ndash1897

[36] Becke AD Density-functional thermochemistry 3 The role ofexact exchange J Chem Phys 1993985648ndash5652

[37] Dueno EE Zambrano CH Shafer W Kass JP 281420-tetradecylpyrogallol[4]arene CCDC Deposit Number 266275Unpublished Results 2005

[38] Kass JP Zambrano CH Zeller M Hunter AD Dueno EE 281420-tetraphenylpyrogallol[4]arene dimethylformamide octasolvateActa Crystallogr Sect E 2006623179ndash3180

[39] Frisch MJ Trucks GW Schlegel HB Scuseria GE Robb MACheeseman JR Scalmani G Barone V Mennucci B Petersson GANakatsuji H Caricato M Li X Hratchian HP Izmaylov AF BloinoJ Zheng G Sonnenberg JL Hada M Ehara M Toyota K Fukuda RHasegawa J Ishida M Nakajima T Honda Y Kitao O Nakai HVreven T Montgomery JA Peralta JE Ogliaro F Bearpark MHeyd JJ Brothers E Kudin KN Staroverov VN Kobayashi RNormand J Raghavachari K Rendell A Burant JC Iyengar SSTomasi J Cossi M Millam NJ Klene M Knox JE Cross JBBakken V Adamo C Jaramillo J Gomperts R Stratmann REYazyev O Austin AJ Cammi R Pomelli C Ochterski JW MartinRL Morokuma K Zakrzewski VG Voth GA Salvador PDannenberg JJ Dapprich S Daniels AD Farkas O Foresman JBOrtiz JV Cioslowski J Fox DJ Gaussian 09 Revision A1Wallingford CT Gaussian Inc 2009

[40] Dennington R II Keith T Millam JM Gauss view ShawneeMission KS Semichem Inc 2007

[41] Zambrano C Thomas R Zeller M Salvatore N Dueno E ActaCrystallogr 2007633452

[42] Prosvirkin AV Kazakova EK Gubaidullin AT Litvinov IA GrunerM Habicher WD Konovalov AI Synthesis of rctt rccc and rcctdiastereomers of calix[4]methylresorcinarenes based on p-tolualde-hyde X-ray diffraction study of the rcct isomer Formation of rcttand rccc cavitands in a cone conformation Russ Chem Bull Int Ed2005542550ndash2557

[43] van der Avoird A Wormer PES Mulder F Bert RM Ab initiostudies of the interaction in van der Waals molecules Top CurrChem 1980931ndash51

[44] Thantiriwatte KS Hohensteins EG Burns LA Sherrill CDAssessment of the performance of DFT and DFT-D methods fordescribing distance dependence of hydrogen-bonded interactionsJ Chem Theory Comput 2011788ndash96

[45] Kawase T Kurata H Ball- bowl- and belt-shaped conjugatedsystems and their complexing abilities exploration of the concavendashconvex pndashp interaction Chem Rev 20061065250ndash5273

[46] Ugliengo P MOLDRAW a program to display and manipulatemolecular and crystal structures Torino 2006 [cited 2012 Feb 15]Available from httpwwwmoldrawunitoit

S Manzano et al334

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