9 June 2000

Chemical Physics Letters 323 Ž2000. 59–70

www.elsevier.nlrlocatercplett

Application of quantum chemical descriptor in quantitative

structure activity and structure property relationship
P. Thanikaivelan, V. Subramanian) , J. Raghava Rao, Balachandran Unni Nair
Chemical Laboratory, Central Leather Research Institute, Adyar, Chennai 600 020, India

Received 14 March 2000; in final form 11 April 2000

Abstract

Various quantum chemical descriptors such as ionisation potential Ž I ., electron affinity Ž A., quantum chemical hardness
index Žh ., softness index Ž S ., electronegativity Ž x . and electrophilicity Ž v . have been used in order to develop a possible
quantitative structure–activity and structure–property relationship ŽQSARrQSPR. model for a series of alkanes. The
correlation between ‘I ’ and boiling point ŽBP. of alkanes ŽC 2 –C 8 . has been found to be y0.984. Among the six selected
descriptors, linear relations derived from ‘I ’ reproduce fairly better experimental values for all the selected macroscopic
properties. Hardness and softness indices exhibit acceptable correlation for all the selected macroscopic properties. They
show promising correlation for heat of formation thereby establishing the fact that hardness is a measure of stability of
molecules. q 2000 Elsevier Science B.V. All rights reserved.

1. Introduction pounds with desired properties can be predicted.

Quantitative Structure–Activity and Structure–
Property Relationship ŽQSARrQSPR. studies have
immense application in the area of chemistry and
biochemistry w1–5x. The main objective of
QSARrQSPR is to transform searches for new
molecules with required properties using chemical
intuition and experience into a mathematically quan-
tified and computerized form w6x. Once a correlation
is established, the structure of any number of com-
)
Corresponding author. Fax: q91-44-491-1589; e-mail:
clrimd@vsnl.comrsubuchem@hotmail.com
Thus QSARrQSPR approaches save resources and
expedite the process of development of new
molecules and drugs. Several quantum descriptors
have been em ployed in establishing the
QSARrQSPR relationship in chemistry and bio-
chemistry w6x. Numerous reviews have been pub-
lished on the applications of quantum descriptors in
QSARrQSPR w3–5x. Methods based on classical
force fields and quantum chemical approaches are
used to determine the geometry and property of the
molecules corresponding to minimum energy confir-
mation w7,8x. A wide variety of semi-empirical and
ab initio methods have been employed to predict a
precise quantitative description of molecular struc-
ture and their chemical properties w6x.

0009-2614r00r$ - see front matter q 2000 Elsevier Science B.V. All rights reserved.
PII: S 0 0 0 9 - 2 6 1 4 Ž 0 0 . 0 0 4 8 8 - 7
60 P. ThanikaiÕelan et al.r Chemical Physics Letters 323 (2000) 59–70
The main objective of this investigation is to
relate the electronic properties derived from quantum
chemical calculation for isolated molecules with their
macroscopic properties. It is well known fact that
these microscopic electronic properties essentially
depend on the geometry of the isolated molecule.
Description of macroscopic properties of a molecule
in bulk from its microscopic property derived from
quantum chemical calculation is an interesting ratio-
nale. Hence, an attempt has been made to identify a
quantum chemical descriptor, which gives good cor-
relation between the calculated and experimentally
found values of macroscopic properties for a series
of alkanes. Six quantum chemical descriptors have
been chosen and individually analysed for the rela-
tion with five selected macroscopic properties of a
series of alkanes. Two kinds of relations, namely
linear and polynomial Ž2nd order., have been made
between the descriptors and macroscopic properties
of series of alkanes.
Based on density functional theory several impor-
tant properties of molecules such as hardness index,
chemical potential, softness index, electronegativity
index, electrophilicity index and Fukui function have
been defined w9–11x. Parr and Chattaraj have used
hardness as a tool to understand chemical reactivity
and other properties of a molecular system w12x. It
was found that stability of molecules is related to
hardness w13,14x. Pauling w15x has introduced the
concept of electronegativity as the power of an atom
in a molecule to attract electrons to itself. Hardness
Žh ., chemical potential Ž m . and electronegativity
index Ž x . are defined as w9,10,16–18x
Em E 2E
hs 1
s 1
2 2
EN VŽr. EN2 VŽr.
EE
ms
EN VŽr.
EE
x s ym s y
EN VŽr.
where E and V Ž r . are electronic energy and external
potential of an N-electron system, respectively. Soft-
ness is a property of molecules that measures the
extent of chemical reactivity. It is the reciprocal of
hardness:
1
Ss Ž 4.
h
Using Koopmans’ theorem for closed-shell
molecules, h , m and x can be redefined as
1 1
hf Ž ´ LUMO y ´ HOMO . f Ž I y A . Ž 5.
2 2
1 1
mf Ž ´ HO MO q ´ LUMO . f y Ž I q A . Ž 6.
2 2
IqA
xs Ž 7.
2
I f y´ HO MO and A f y´ LUMO Ž 8.
where I and A are the ionization potential and
electron affinity of the molecules. Electron affinity
refers to the capability of a ligand to accept precisely
one electron from a donor. However, in many kinds
of bonding viz. covalent, dative or hydrogen bond-
ing, partial charge transfer takes place. Parr et al.
w11x have proposed electrophilicity index as a mea-
sure of energy lowering due to maximal electron
flow between donor and acceptor. They have pro-
posed electrophilicity index Ž v . as a function of the
square of electronegativity divided by hardness:
m2
vs Ž 9.
2h
Numerous applications are available on the use of
the HOMOy LUMO gap as a quantum descriptor in
establishing correlation in various chemical and bio-
Ž 1. chemical systems w19–23x. In the previous studies
several attempts have been made to relate atomic
radius of atoms using electrostatic potential and elec-
tronegativity w24x. Using the quadratic Euler–
Ž 2. Lagrange equation, the atomic radii have been pre-
dicted from atomic densities. The predicted radii
have been used to relate the experimental covalent
Ž 3. radii and other physical properties like softness, elec-
tronegativity etc. Since alkanes are generally used as
a starting point for QSARrQSPR models, an attempt
has been made to obtain correlation between several
quantum chemical descriptors of series of alkanes
with their macroscopic properties in this work.
 P. ThanikaiÕelan et al.r Chemical Physics Letters 323 (2000) 59–70 61

2. Computational details Table 1

Abbreviations of the selected alkanes and their isomers ŽC 2 –C 8 .
All calculations have been performed using the Abbreviation IUPAC name
GAUSSIAN 94W suite program w25x. The Hartree– 2 ethane
Fock method has been used to optimize the geometry 3 propane
of alkanes using the 6-31G U basis set. Employing 4 butane
2M3 2-methyl propane
Koopmans’ approximation Žunrelaxed orbitals., ioni- 5 pentane
sation potential Ž I . and electron affinity Ž A. have 2M4 2-methyl butane
been calculated. Using these values various quantum 22MM3 2,2-dimethyl propane
chemical descriptors, namely hardness, softness, 6 hexane
electronegativity and electrophilicity, have been 2M5 2-methyl pentane
3M5 3-methyl pentane
computed using Eqs. Ž4. – Ž9.. The physical proper- 23MM4 2,3-dimethyl butane
ties of alkanes have been taken from the literature 22MM4 2,2-dimethyl butane
w26x. A standard regression analysis package has 7 heptane
been used to develop QSARrQSPR models for the 2M6 2-methyl hexane
physical properties of alkanes with all the selected 3M6 3-methyl hexane
3E5 3-ethyl pentane
descriptors. 24MM5 2,4-dimethyl pentane
22MM5 2,2-dimethyl pentane
23MM5 2,3-dimethyl pentane
3. Results and discussion 33MM5 3,3-dimethyl pentane
223MMM4 2,2,3-trimethyl butane
8 octane
Alkanes being simple organic compounds are 2M7 2-methyl heptane
generally employed for QSPR analysis. The alkanes 3M7 3-methyl heptane
used are in the range of C 2 –C 8 along with their 4M7 4-methyl heptane
isomers. Table 1 provides the name of the selected 25MM6 2,5-dimethyl hexane
alkanes and their abbreviations that have been used 3E6 3-ethyl hexane
24MM6 2,4-dimethyl hexane
in this study. In order to obtain an extensive structure 22MM6 2,2-dimethyl hexane
property relationship, five macroscopic properties 23MM6 2,3-dimethyl hexane
were selected for the analysis, viz. boiling point, BP 34MM6 3,4-dimethyl hexane
Ž8C.; heat of formation, D Hf 8 Žkcal moly1 .; entropy, 33MM6 3,3-dimethyl hexane
S8 Žcal Ky1 moly1 .; heat capacity, C p Žcal Ky1 2M3E5 2-methyl-3-ethyl pentane
224MMM5 2,2,4-trimethyl pentane
moly1 . at 258C; and heats of vaporization, D Hv Žcal 234MMM5 2,3,4-trimethyl pentane
moly1 .. From the ionisation potential and electron 3M3E5 3-methyl-3-ethyl pentane
affinity values, remaining quantum chemical descrip- 223MMM5 2,2,3-trimethyl pentane
tors have been calculated for C 2 –C 8 alkanes and 233MMM5 2,3,3-trimethyl pentane
2233MMMM4 2,2,3,3-tetramethyl butane
their isomers using Eqs. Ž4. – Ž9..
Figs. 1–5 show the plot of quantum chemical
descriptor values versus experimental macroscopic
property for C 2 –C 8 alkanes. The points were fitted
for linear and polynomial Ž2nd order. relation using Table 1, with the exception of heat capacity Žsample
a standard regression analysis package. The resulting number is 28..
regression equations and statistical parameters are It can be seen from Table 2 that among all the
given in Table 2. In the regression equations, ‘ x’ microscopic properties, ionisation potential holds the
refers to the value of the quantum chemical descrip- correlation coefficient greater than 0.95 for all the
tor. In Table 2, r and SD represent the correlation macroscopic properties in a linear fit. For boiling
coefficient and standard deviation, respectively. The point it attains a maximum correlation coefficient of
number of samples Žalkanes. taken for the analysis y0.984. The negative sign indicates the characteris-
for each macroscopic property is 39 as given in tic of the slope i.e. whether the curve is of increasing
62 P. ThanikaiÕelan et al.r Chemical Physics Letters 323 (2000) 59–70

or decreasing order. A polynomial fit does not alter the points approach a coherent linear fit as seen from
the relation drastically. This is due to the fact that all Fig. 1a–e for all the five macroscopic properties.

Fig. 1. Plot of experimental macroscopic property vs. I indices of C 2 –C 8 alkanes Ža. Boiling point ŽBP.. Žb. Heat of formation Ž D Hf 8.. Žc.
Entropy Ž S8.. Žd. Heat capacity Ž C p .. Že. Heat of vaporisation Ž D H v .. , linear fit; P P P , polynomial fit Žsecond order.. The same
conventions are used in Figs. 2–5.
 P. ThanikaiÕelan et al.r Chemical Physics Letters 323 (2000) 59–70 63

The regression equations resulting from the linear fit experimental and calculated values of the five se-
were used to calculate the macroscopic properties lected macroscopic properties. The calculated values
using the ionisation potential values for the series of do not deviate too much from the already reported
alkanes. Table 3 shows the comparison between experimental values. For some of the higher molecu-

Fig. 2. Plot of experimental macroscopic property vs. A indices of C 2 –C 8 alkanes.

64 P. ThanikaiÕelan et al.r Chemical Physics Letters 323 (2000) 59–70

lar weight isomers the experimental heat capacity
values were not available from the literature w26x. For
those isomers the ionisation potential descriptor pre-
dicts the heat capacity values that can be compared
with the experimental values.
Hardness and softness indices exhibit more or less
same correlation coefficient for all the macroscopic
properties as observed from Table 2, though the
regression equations are not equal. This is due to the
fact that softness is the inverse of hardness. This has

Fig. 3. Plot of experimental macroscopic property vs. h indices of C 2 –C 8 alkanes.

 P. ThanikaiÕelan et al.r Chemical Physics Letters 323 (2000) 59–70 65

been further confirmed from the figures where mir- However, plots of softness indices versus experimen-
ror image curves of hardness and softness indices for tal macroscopic properties are not given, since the
similar macroscopic properties are clearly perceived. curves are mirror images of hardness index plots.

Fig. 4. Plot of experimental macroscopic property vs. v indices of C 2 –C 8 alkanes.

66 P. ThanikaiÕelan et al.r Chemical Physics Letters 323 (2000) 59–70

The ‘r ’ values are in the range of 0.80–0.95. As lation coefficient for heat of formation. This con-
expected the correlation coefficient values are not firms the fact that hardness is a direct measure of
altered drastically by a polynomial fit for both the stability of molecules as shown in the maximum
indices. Both of the indices show a maximum corre- hardness principle w27x and softness is a direct mea-

Fig. 5. Plot of experimental macroscopic property vs. x indices of C 2 –C 8 alkanes.

 P. ThanikaiÕelan et al.r Chemical Physics Letters 323 (2000) 59–70 67

Table 2
Regression equations and statistical parameters of the six quantum chemical descriptors for the five macroscopic properties
Descriptor Macroscopic Linear fit Polynomial fit
property Regression equation r SD Regression equation r SD
I BP y3 475 x q1585.8 y0.984 8.7 4 337.7 y15 789.1 x q 13 748.70 x 2 0.987 8.0
D Hf 8 569.1 x y292.5 0.963 2.2 y1 101.7 q4189.8 x y 4042.50 x 2 0.973 1.9
S8 y908.7x q489.5 y0.945 4.4 1 750.5 y6551.2 x q 6299.90 x 2 0.953 4.2
Cp y574.4 x q286.9 y0.973 2.1 1 449.7 y5750.7x q 5750.40 x 2 0.989 1.3
D Hv y99 707.7x q51 347.9 y0.958 423.1 221 271.1 y860 061.5 x q 848 939.60 x 2 0.970 358.9
A BP 2 913.2 x q724.9 0.468 44.0 y12 585.4 y116 765.2 x y 268 685.50 x 2 0.676 37.2
D Hf 8 y681.9 x y196.9 y0.655 6.3 1 424.9 q13 900.9 x q 32 739.30 x 2 0.745 5.6
S8 583.1 x q224.7 0.344 12.8 y3 494.3 y32 856.2 x y 75 073.30 x 2 0.607 10.9
Cp 565.9 x q161.9 0.539 7.5 y1 451.8 y13 907.9 x y 32 418.10 x 2 0.651 6.9
D Hv 80 742.8 x q26 014.9 0.440 1320.2 y316 142.9 y2 995 749.3 x y 6 906 913.30 x 2 0.612 1179.0
h BP y4 396.7x q1519.4 y0.886 23.1 y2 293.7 q18 311.2 x y 33 757.00 x 2 0.893 22.7
D Hf 8 784.4 x y302.7 0.945 2.7 y421.2 q1490.3 x y 1049.30 x 2 0.945 2.7
S8 y1 090.6 x q452.7 y0.807 8.0 y676.5 q5634.4 x y 9997.30 x 2 0.816 7.9
Cp y771.1 x q290.4 y0.912 3.6 579.0 y2479.2 x q 2523.20 x 2 0.914 3.7
D Hv y125 036.5 x q49 075.7 y0.855 763.5 9 547.2 q110 365.7x y 349 941.10 x 2 0.856 771.8
S BP 491.0 x y1421.1 0.879 23.7 y7 356.4 q4469.1 x y 665.70 x 2 0.896 22.5
D Hf 8 y88.2 x q223.8 y0.945 2.7 459.4 y246.1 x q 26.40 x 2 0.945 2.7
S8 121.6 x y276.1 0.799 8.2 y1 998.3 q1275.9 x y 193.20 x 2 0.820 7.9
Cp 88.0 x y231.0 0.913 3.6 y283.0 q123.1 x y 5.91 x 2 0.913 3.7
D Hv 14 019.5 x y34 716.7 0.851 771.5 y133 607.9 q80 300.8 x y 11 091.30 x 2 0.857 768.8
x BP y7 660.4 x q890.2 y0.883 23.4 y1 768.0 q41 273.9 x y 224 422.60 x 2 0.900 22.0
D Hf 8 1 055.2 x y157.5 0.729 5.7 375.4 y8753.5 x q 44 985.60 x 2 0.757 5.5
S8 y2 177.0 x q326.0 y0.921 5.3 37.9 q3125.3 x y 24 318.20 x 2 0.924 5.3
Cp y1 164.3 x q160.5 y0.812 5.2 y155.7 q4633.4 x y 26 484.00 x 2 0.821 5.2
D Hv y222 566.5 x q31 682.5 y0.870 725.5 y34 002.7 q986 593.8 x y 5 545 572.80 x 2 0.882 702.1
v BP y22 348.4 x q462.1 y0.728 34.2 y133.8 q45 389.2 x y 1 907 764.60 x 2 0.738 34.1
D Hf 8 2 708.5 x y92.2 0.527 7.1 7.5 y8617.9 x q 318 998.90 x 2 0.541 7.1
S8 y6 674.1 x q209.9 y0.798 8.2 130.6 q2333.4 x y 253 688.00 x 2 0.799 8.2
Cp y3 246.2 x q92.3 y0.641 6.9 81.2 y1994.6 x y 35 030.20 x 2 0.641 6.9
D Hv y655 682.1 x q19 352.5 y0.724 1014.5 77.6 q1 535 610.5 x y 61 715 697.10 x 2 0.736 1009.0

sure of reactivity of molecules; while heat of forma-
tion is the property that measures the heat required
for the formation of a molecule. Indeed one can
relate the easiness of the formation of the molecule
to the softness and the stability of the formed
molecule to the hardness. Table 4 shows the experi-
mental and calculated values of heat of formation
using hardness as a descriptor. It can be observed
from the table that hardness index provides compara-
ble values for heat of formation for the series of
alkanes. Though the correlation coefficient for hard-
ness index is lower, by 0.018 units, than the ionisa-
tion potential index, hardness indexes exhibit better
theoretical Žcalculated. values for more than 45% of
the selected alkanes when compared to that of the
ionisation potential index.
The electronegativity index exhibits correlation
coefficients in the range of 0.73–0.92 for all the
macroscopic properties. It displays a maximum cor-
relation coefficient for entropy. Unlike hardness and
softness indices, electronegativity index exhibits a
lower correlation coefficient for heat of formation.
There is a slight increase in the correlation coeffi-
cient values when a polynomial fit has been em-
ployed.
Electron affinity and electrophilicity indices ex-
hibit poor correlation coefficients in the range of
0.35–0.66 and 0.53–0.80, respectively, for all the
68 P. ThanikaiÕelan et al.r Chemical Physics Letters 323 (2000) 59–70

Table 3
Experimental and calculated values of five selected macroscopic properties of C 2 –C 8 alkanes and their isomers using ionisation potential as
a descriptor a
Alkanes I ŽeV. BP Ž8C. D Hf 8 Žkcal moly1 . S8 Žcal Ky1 C p Žcal Ky1 D H v Žcal moly1 .
Exp. Cal. Exp. Cal. moly1 . moly1 . at 258C
Exp. Cal. Exp. Cal. Exp. Cal.
2 0.48623 y88.630 y103.8 y20.24 y15.8 54.85 47.7 12.5 7.6 3 739.5 2867.0
3 0.46888 y42.070 y43.6 y24.82 y25.7 64.51 63.4 17.4 17.6 4 811.8 4596.9
4 0.45585 y0.500 1.7 y29.81 y33.1 74.10 75.3 23.3 25.1 5 801.2 5896.1
2M3 0.45858 y11.730 y7.8 y32.10 y31.5 70.42 72.8 23.1 23.5 5 416.2 5623.9
5 0.44584 36.074 36.5 y35.00 y38.8 83.27 84.4 28.6 30.8 6 595.1 6894.2
2M4 0.44527 27.852 38.4 y36.50 y39.1 82.10 84.9 28.4 31.1 6 470.8 6951.1
22MM3 0.45101 9.503 18.5 y40.20 y35.8 73.10 79.7 28.8 27.8 5 648.6 6378.7
6 0.43734 68.740 66.0 y39.96 y43.6 92.45 92.1 34.0 35.7 7 627.2 7741.7
2M5 0.43817 60.271 63.1 y41.50 y43.1 91.00 91.3 33.9 35.2 7 676.6 7659.0
3M5 0.43666 63.282 68.4 y40.90 y43.9 91.50 92.7 33.4 36.1 7 743.9 7809.5
23MM4 0.43669 57.988 68.3 y42.10 y43.9 87.40 92.7 33.3 36.1 7 120.0 7806.5
22MM4 0.43723 49.741 66.4 y43.90 y43.7 85.60 92.2 33.8 35.8 7 271.0 7752.7
7 0.43102 98.427 88.0 y44.89 y47.2 101.64 97.8 39.4 39.3 8 409.6 8371.9
2M6 0.43187 90.052 85.0 y46.40 y46.7 100.40 97.1 39.3 38.8 8 538.7 8287.1
3M6 0.42981 91.850 92.2 y45.90 y47.9 101.80 98.9 39.1 40.0 8 596.3 8492.5
3E5 0.43068 93.475 89.2 y45.20 y47.4 98.30 98.1 39.6 39.5 8 642.8 8405.8
24MM5 0.43032 80.500 90.4 y48.10 y47.6 94.80 98.5 40.8 39.7 8 167.1 8441.7
22MM5 0.43182 79.197 85.2 y49.00 y46.8 93.80 97.1 39.8 38.9 8 106.7 8292.1
23MM5 0.42885 89.784 95.5 y46.30 y48.4 99.00 99.8 38.4 40.6 8 390.9 8588.3
33MM5 0.42977 86.064 92.3 y47.60 y47.9 95.10 98.9 39.6 40.0 8 145.4 8496.5
223MMM4 0.42916 80.882 94.5 y48.60 y48.3 91.60 99.5 39.0 40.4 7 767.1 8557.3
8 0.42612 125.655 105.0 y49.82 y49.9 110.82 102.3 44.8 42.1 9 221.0 8860.5
2M7 0.42679 117.647 102.7 y51.50 y49.6 108.81 101.7 44.7 41.8 9 362.0 8793.7
3M7 0.42532 118.925 107.8 y50.82 y50.5 110.32 103.0 44.4 42.6 9 432.0 8940.2
4M7 0.42432 117.709 111.3 y50.69 y51.0 108.35 103.9 44.7 43.2 9 404.8 9039.9
25MM6 0.42803 109.103 98.4 y53.21 y48.9 104.93 100.5 – 41.0 9 110.2 8670.0
3E6 0.42555 118.534 107.0 y50.40 y50.3 109.51 102.8 – 42.5 9 416.3 8917.3
24MM6 0.42361 109.429 113.8 y52.44 y51.4 106.51 104.6 – 43.6 9 086.6 9110.7
22MM6 0.42678 106.840 102.7 y53.71 y49.6 103.06 101.7 45.0 41.8 8 927.8 8794.6
23MM6 0.42362 115.607 113.7 y51.13 y51.4 106.11 104.6 – 43.6 9 224.9 9109.7
34MM6 0.42183 117.725 119.9 y50.91 y52.4 107.15 106.2 – 44.6 9 239.4 9288.2
33MM6 0.42401 111.969 112.4 y52.61 y51.2 104.70 104.2 45.6 43.3 9 065.2 9070.8
2M3E5 0.42587 115.650 105.9 y50.48 y50.1 105.43 102.5 – 42.3 9 134.3 8885.4
224MMM5 0.42449 99.238 110.7 y53.57 y50.9 101.62 103.8 45.0 43.1 8 548.0 9022.9
234MMM5 0.42392 113.467 112.7 y51.97 y51.2 102.99 104.3 – 43.4 8 988.2 9079.8
3M3E5 0.42292 118.259 116.2 y51.38 y51.8 103.48 105.2 – 43.9 9 028.7 9179.5
223MMM5 0.4236 109.840 113.8 y52.61 y51.4 101.62 104.8 – 43.6 8 861.1 9111.7
233MMM5 0.42357 114.760 113.9 y51.73 y51.4 103.14 104.6 – 43.6 8 960.9 9114.7
2233- 0.42325 106.470 115.0 y53.99 y51.6 94.34 104.9 – 43.8 10 351.5 9146.6
MMMM4
a
M, methyl; E, ethyl.

macroscopic properties when compared to the other
descriptors using a linear model. In this work, elec-
tron affinity has been obtained from a Hartree–Fock
calculation within the limit of Koopmans’ approxi-
mation. The proper inclusion of electron correlation
and relaxation of orbitals are necessary to obtain
reliable estimation of ‘ A’. These errors may also
responsible for the poor correlation obtained for
electron affinity. Polynomial fit increases the correla-
tion coefficient values for the electron affinity de-
 P. ThanikaiÕelan et al.r Chemical Physics Letters 323 (2000) 59–70 69

Table 4
Experimental and calculated values of heat of formation of C 2 –C 8 alkanes and their isomers using hardness as a descriptor a
Alkanes h ŽeV. Exp. Cal.
2 0.36510 y20.24 y16.32
3 0.35144 y24.82 y27.03
4 0.34432 y29.81 y32.62
2M3 0.34094 y32.10 y35.27
5 0.33852 y35.00 y37.16
2M4 0.33484 y36.50 y40.05
22MM3 0.33138 y40.20 y42.77
6 0.33369 y39.96 y40.95
2M5 0.33192 y41.50 y42.34
3M5 0.33032 y40.90 y43.60
23MM4 0.32967 y42.10 y44.11
22MM4 0.32526 y43.90 y47.57
7 0.33001 y44.89 y43.84
2M6 0.32877 y46.40 y44.81
3M6 0.32751 y45.90 y45.80
3E5 0.33011 y45.20 y43.76
24MM5 0.32597 y48.10 y47.01
22MM5 0.32338 y49.00 y49.04
23MM5 0.32356 y46.30 y48.89
33MM5 0.32146 y47.60 y50.54
223MMM4 0.32098 y48.60 y50.92
8 0.32718 y49.82 y46.06
2M7 0.32614 y51.50 y46.88
3M7 0.32522 y50.82 y47.60
4M7 0.32525 y50.69 y47.57
25MM6 0.32595 y53.21 y47.02
3E6 0.32628 y50.40 y46.77
24MM6 0.32257 y52.44 y49.68
22MM6 0.32099 y53.71 y50.92
23MM6 0.32163 y51.13 y50.41
34MM6 0.32120 y50.91 y50.75
33MM6 0.31942 y52.61 y52.15
2M3E5 0.32562 y50.48 y47.28
224MMM5 0.31472 y53.57 y55.83
234MMM5 0.32012 y51.97 y51.59
3M3E5 0.31487 y51.38 y55.72
223MMM5 0.31844 y52.61 y52.92
233MMM5 0.31853 y51.73 y52.85
2233MMMM4 0.31620 y53.99 y54.67
a
M, methyl; E, ethyl.

scriptor and gives a maximum coefficient value of
0.745 for heat of formation. However the increase in
correlation coefficient is not drastic due to the scat-
tering of points that limit the curve fitting.
4. Conclusion
In this study an attempt has been made to identify
a possible quantum chemical descriptor for develop-
ing QSARrQSPR models. The present study reveals
that ionisation potential can be used as a descriptor
to understand structure activity and structure prop-
erty relationship. Within the framework of Hartree–
Fock theory, the computed I has excellent correla-
tion with the macroscopic properties such as boiling
point, heat of formation or enthalpy, entropy, heat
capacity and heat of vaporisation. The correlation
coefficient has been found to be high for the rela-
70 P. ThanikaiÕelan et al.r Chemical Physics Letters 323 (2000) 59–70
tionship between I and BP. Hardness and softness
indices exhibit similar correlation coefficients in the
range of 0.80–0.95 for all the macroscopic proper-
ties, which confirms the fact that both the micro-
scopic properties are interrelated. Maximum correla-
tion coefficients for both the indices have been found
to be 0.945 for heat of formation. This observation
reinforces the existing fact that, hardness Žh . holds a
direct relationship with the stability of a molecule.
Other descriptors do not show a promising relation-
ship with the selected macroscopic properties. Hence
from this study it can be concluded that ionisation
potential can be used as a successful quantum chemi-
cal descriptor for developing QSARrQSPR models
while hardness index shows some promising results
for specific macroscopic properties.
Acknowledgements
One of the authors ŽV.S.. thanks the Council of
Scientific and Industrial Research ŽCSIR., India and
Department of Science and Technology ŽDST., Gov-
ernment of India for financial assistance. P.T. and
V.S. wish to thank Dr. T. Ramasami, Director, Cen-
tral Leather Research Institute, India for his interest
and encouragement. Authors also thank Prof. P.K.
Chattaraj and Prof. S.R. Gadre for their valuable
suggestions.
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