Indian Journal of ChemistryVol. 35A, April 1996, pp. 270-280
Transfer energetics of some nucleosides in aqueous mixturesof urea and glycerol
Sonali Ganguly & Kiron K Kundu"
Physical Chemistry Laboratories, Jadavpur University, Calcutta 700 032, India
Received 27 March 1995; revised 26 September 1995; accepted 16 October 1995
Standard free energies (~G~) and entropies (.1.S~) of transfer of some nucleosides viz. adenosine(ado), guanosine (guo) and xanthosine (xao) from water to aqueous mixtures of urea (UH) and glycerol(GL) have been evolved from solubilities measured at different temperatures. The observed .1.G?-composition profiles show increasing stabilization for the nucleosides in both the co solvent systems. TheT.1. S~-composition profiles are, however, complicated. So, after the elimination of various interactioneffects, viz. cavity, dipole-dipole, dipole-induced dipole and dispersion interactions, the results havebeen discussed in the light of the hydrophilic-hydrophobic hydration effect. The solvation behaviour ofthe nucleosides in UH-water and GL-water mixtures help understand the relative stability of the doublestranded nucleic acid helix in these. two cosolvent systems.
The nucleosides and nucleotides are the buildingblocks of nucleic acids I. The two strands of a nuc-leic acid helix are held together by H-bonds be-tween complimentary base pairs of purines andpyrimidines. In addition, virtually all the surfaceatoms in the ribose and phosphate groups formH-bonds to water molecules. Several studies!"have examined the effects of aqueous urea (UH)and glycerol (GL) on denaturation of doublestranded nucleic acid helix. These investigationswere done in terms of change in intrinsic viscos-ity', rise in denaturation temperature), thermody-namics of unwinding of DNA helix4,5 etc.
In a previous paper? we have reported the sol-vation behaviour of the nucleic acid bases in aque-ous UH and GL in order to understand the stabil-ity of DNA-RNA double helix in these two cosol-vent systems as compared to water. In this paper,we extend the same study to nucleosides with theexpectation that the knowledge of relative solva-tion of the nucleosides should be a better yard-stick in unfolding the role of aqueous UH and GLtowards stability of the double helix structure, ascompared to that for nucleic acid bases alone.Therefore, as in our previous paper", we evaluatethe transfer free energies(~G~)) and transfer entropies (~Sn of the threenucleosides viz. adenosine (ado), guanosine (guo)and xanthosine (xao) [vide Fig. 1 (a-cj], from waterto a series of aqueous mixtures of UH and GL,from the measured solubilities of the same at five
o
(a) adenosine (b) guanosine
o
(e) xa nth c slne
Fig. I-Structure of adenosine, guanosine and xanthosine
equidistant temperatures ranging between 15-35°C. But these ~ Gi) and .1.Si~ values includeseveral interactions like dipole-dipole, dipole-in-duced dipole and dispersion interactions besidescavity effect. So, on elimination of the above men-tioned interaction effects from ~ G~)and T~ Si) va-lues, results are interpreted in terms of hydrophil-ic-hydrophobic hydration effect and in the case of
GANGULY et al.: TRANSFER ENERGETICS OF SOME NUCLEOSIDES 271
transfer entropies, in the light of solvent-structu-redness as well.
Materials and MethodsThe nucleosides adenosine (grade A92 51 ),
guanosine (grade G-6752) and xanthosine (gradeX-0750, Sigma, USA) and were used as such afterdrying in a vacuum desiccator kept at 0-5°C. Thepurities of the chemicals were checked by UVspectroscopy?" and were found to lie within 98-99%. Drying of UH (A.R., S.D.) and purificationof GL (AR, S.D.) were similar to that describedearlier":". Triply distilled CO, free water was used.Measurements of saturated s-olubilities of differentsolutions were the same as that described in ourprevious papers":". The required values for Amax
and molar absorptivity were taken from the litera-ture ':", The average uncertainty involved in themeasured solubilities of these nucleosides was± 1%.
ResultsThe observed solubilities (S, mol dm -1) of ado,
guo and xao at different temperatures in water,UH-water and GL-water mixtures are presented inTable 1. As in our previous papers"?", assumingthe degree of ionization of these nucleosides to bezero in water and mixed solvents, and the activitycoefficient (y) of the saturated solutions of the nu-cleosides in the respective solvents be unity, thefree energy of solutions (~G~) of each solute wascomputed on the molar scale by the relation~ G~= - R T In S ... (1)
The values at different temperatures in each sol-vent were fitted by the method of least squares toan equation of the form
~ G~= a+ st» cTIn T ... (2)
where T is the absolute temperature. The valuesof the coefficients a, band c are listed in Table 2.These reproduce the experimental data towithin ± 0.03 kJ mol-I. The standard free energies(~G~)and entropies (~S; ) of transfer from water tothe cosolvents were computed at 25°C on mole frac-tion scale using the relations 3 and 4 respectively
~ G\I= s~ G~ - w~ G~
= (as - awl + ib, - bw)T+ (c, - cw)TIn T
- RTIn (MsPwIMwp, ... (3)
~ 5\1 = s~ S~- w~ S~
= (bw - bJ + (cw - cJ( 1 + In T)
... (4)
where T= 298.15 K, M, the molar mass, p, densityin kg dm -.1 and a stands for coefficient of thermalexpansion of the solvents. The subscripts sand wrefer to the solvent mixtures and water respect-ively. The values for p and a at 25°C are knownfrom the literaturev", ~ G\I and T~ 5\1 values aregiven in Table 2. The standard deviations basedon uncertainty in S = ± 1% in ~ G\I and ~ 5:1 ascalculated by Please's method 12 are ± 0.05 kJmol- I and ± 2 JK - Imol- I respectively.
DiscussionFree energies of transfer
Figure 2 (inset) shows the variation of ~ G? ofado, guo and xao with composition of aqueousmixtures of UH (solid lines) and GL (brokenlines). In both the solvent systems we witness in-creasingly negative ~ G?-composition profiles indi-cating increasing stabilization of the nucleosides inthese two solvent systems. But the profiles foraqueous UH show more increased stabilizationthan for aqueous GL.
Since free energy of transfer due to interactioneffects, (~G:I. int) is considered to be a better indi-cator of solute solvent interactions'vl'":" first wecalculate the cavity effect (~G\I. cavl based on thescaled particle theory (SPT)13 and deduct it from~ G\I to obtain values for ~ G\J.intoFigure 2 showsthe ~ G\l,int-composition profiles for the nucleo-sides in both UH-water and Gl.-water mixtures.While curves for aqueous UH illustrate increasedstabilization, the same for aqueous GL show dec-reased stabilization indicating that the nucleosidesare less solvated than in aqueous UH.
Further, in order to understand the relative be-haviour of the nucleosides in aqueous UH and GLin terms of hydrophilic-hydrophobic hydration(H1HbH) effect, various involved interactions are tobe excluded". So, we estimated free energies oftransfer due to dipole-dipole (~G~. dip) dipole-in-duced dipole (~G:l, ind) and dispersion (~G?, disp).interaction effects based on formulations as de-picted in literature't"-":". The hard sphere diame-ters for ado, guo and xao were taken to be 1.02,1.06, and 1.06 nm respectively. These values weretentatively computed from the structural geometryand appropriate orientation of the molecules andconsidering the appropriate bond lengths andbond angles":". The dipole moment and pol ariza-bility values were taken from the literature17,19,20.
As the dipole moment for xao was not available,its value was assumed to be equal to that for xan-thine. This was done based on the fact that the
272 INDIAN J CHEM, SEe. A, APRIL 1996
Table I-Solubilities (S in mol dm-J) of ado, guo and xao in water and aqueous mixtures of UH and GL at differenttemperatures
Compound 15 20 25 30 35°C
Waterado 0.0276 0.0298 0.0331 0.0372 0.043~guo 0.0021 0.0028 0.0038 0.0048 0.0061xao 0.0030 0.0033 0.0035 0.0037 0.0038-
5.00wt%UHado 0.0277 0.0310 0.0333 0.0379 0.0444guo 0.0038 0.0046 0.0054 0.0069 0.0075xao 0.0070 0.0086 0.0100 0.0111 0.0135
1l.52wt%UHado 0.0277 0.0305 0.0346 0.0395 0.0479guo 0.0050 0.0061 0.0072 0.0086 0.0111xao 0.0129 0.0163 0.0203 0.0243 0.0296
15.00wt%UHado 0.0300 0.0350 0.0411 0.0468 0.0553guo 0.0065 0.0081 0.0091 0.0105 0.0110xao 0.1900 0.0240 0.0281 0.0320 0.0391
20.31 wt% UHado 0.0341 0.0441 0.0542 0.0603 0.0662guo 0.0092 0.0103 0.0112 0.0120 0.0126xao 0.0283 0.0345 0.0420 0.0470 0.0504
25.00wt%UHado 0.0420 0.0532 0.0644 0.0718 0.0770guo 0.0117 0.0140 0.0160 0.0173 0.0191xao 0.0313 0.0391 0.0486 0.0509 0.0605
29.64 wt% UHado 0.0508 0.0658 0.0778 0.0811 0.0844guo 0.0126 0.0137 0.0167 0.0197 0.0244xao 0.0316 0.0423 0.0535 0.0622 0.0720
35.00.wt % UHado 0.0749 0.0870 0.0979 0.1040 0.1070guo 0.0280 0.0290 0.0320 0.0340 0.0358xao 0.0361 0.0470 0.0601 0.0725 0.0811
36.83 wt% UHado 0.0920 0.0995 0.1061 0.1112 0.1157guo 0.0372 0.0384 0.0395 0.0407 0.0422xao 0.0363 0.0497 0.0643 0.0762 0.0820
5wt%GLado 0.0282 0.0310 0.0346 0.0410 0.0485guo 0.0025 0.0035 0.0041 0.0052 0.0062xao 0.0030 0.0031 0.0036 0.0037 0.0038
lOwt%GLado 0.0296 0.0334 0.0386 0.0459 0.0596guo 0.0026 0.0037 0.0050 0.0057 0.0062xao 0.0030 0.0033 0.0036 0.0037 0.0038
20wt%GLado 0.0330 0.0365 0.0428 0.0498 0.0620guo 0.0064 0.0067 0.0071 0.0082 0.0094
exao 0.0036 0.0043 0.0044 0.0048 0.0050
(contd)
GANGULY et al: TRANSFER ENERGETICS OF SOME NUClEOSIDES 273
Table I-Solubilities (S in mol dm-l) of ado, guo and xao in water and aqueous mixtures of UH and GL at differenttemperatures-Contd
Compound 15 20 25 30 35·
30wt%GLado 0.0356 0.0402 0.0474 0.0565 0.0694guo 0.0098 0.0101 0.0104 0.0108 0.0112xao 0.0040 0.0047 0.0052 0.0058 0.0059
4Owt%GLado 0.0371 0.0420 0.0497 0.0602 0.0740guo 0.0100 0.0109 0.On5 0.0142 0.0161xao 0.0046 0.0054 0.0059 0.0063 0.0066
50wt%GLado 0.0370 0.0431 0.0520 0.0631 0.0782guo 0.0106 0.0130 0.0155 0.0183 0.0216xao 0.0050 0.0057 0.0064 0.0068 0.0072
60wt%GLado 0.0399 0.0480 0.0585 0.0742 0.0956guo 0.0281 0.0290 0.0300 0.0331 0.0354xao 0.0057 0.0066 0.0075 0.0079 0.0083
70wt%GLado 0.0402 0.0513 0.0656 0.0820 0.1060guo 0.0360 0.0372 0.0383 0.0393 0.0402xao 0.0062 0.0074 0.0084 0.0089 0.0094
Table 2-Coefficients a, band cof Eq. (2) and transfer energetics (d G:' and TdS:' in kJ mol " ")of ado,guo and xao from water toaqueous mixtures of UH and GL at 25° (mole fraction scale)
Compound a(kJmol-') b(kJmol-'K-I) £{kJmol-'K-I) dG~ TdS~Water
ado -231.08 5.2249 -0.776069guo 171.97 -3.0638 0.444669xao IMUl2 - 3.5631 0.534702
5.00wt%UH •ado - 190.23 4.7633 -0.715560 -om 16.80guo 142.99 - 2.6689 0.391854 -0.97 -6.42xao 45.89 -0.5521 0.076667 -2.48 16.92
11.52wt%UHado -271.69 6.5159 -0.978777 -0.17 20.23guo - 188.21 4.8179 -0.727609 -1.78 -8.66xao 1I0.78 -1.8754 0.269705 -4.37 26.37
15.00wt%UHado -18.26 0.8642 -0.136297 -0.54 22.60guo 354.37 -7.5563 1.124450 -2.27 -18.01xao 94.04 - 1.5961 0.230001 -5.13 21.99
20.31 wt% UHado -1I2.23 3.1468 -0.481958 -1.36 32.68guo 168.28 -3.5236 0.525971 -2.94 -24.83xao 408.24 -8.7347 1.297418 -6.28 19.26
25.00 wt % UHado 504.69 -10.8913 1.618529 -1.50 23.32guo 231.01 -4.8173 0.715560 -3.59 -18.13xao 395.34 - 8.3868 1.243711 -6.45 22.37
(contd)
274 INDIAN J CHEM, SEC. A, APRIL 1996
Table 2-Coefficients a, band cofEq. (2) and transfer energetics (a G~ and TaS? in kJ mol-I) ofado,guo and xao from water toaqueous mixtures ofUH and GL at 25· (mole fraction scale)--Contd
Compound a (kJ mol-I) b(kJ mol-'K-') "kJ mol-IK-1) so; TaS~
29.64wt%UHado 689.01 -15.1171 2.251427 -2.33 19.90
guo -309.84 7.4729 - 1.123238 -4.14 -10.08
xao 440.40 -9.2988 1.377115 -7.06 28.4035.00wt% UH
ado 373.62 -8.1256 1.209637 -2.56 15.22
guo -10.72 0.4527 -0.068149 - 5.39 -24.40
xao 436.48 -9.2062 1.362971 -7.02 28.5336.83wt% UH
ado 110.55 - 2.3050 0.342767 -3.30 11.45
guo -18.13 0.5219 -0.076244 -6.42 - 28.27
xao 687.22 -14.8402 2.204149 -7.61 29.17
5wt%GLado -284.36 6.8049 -1.022223 -0.36 20.48
guo 352.92 -7.2538 1.073340 -0.35 -6.14
xao 133.03 - 2.760\ 0.414343 -0.03 0.93IOwt%GL
ado -416.31 9.8678 -1.482139 -0.50 25.87guo 858.29 -18.6314 2.772556 -0.84 -6.81xao 238.92 -5.1566 0.772672 -0.10 0.14
20wt%GLado - 316.72~ 7.5880 -1.140807 0.68 23.78guo -447.44 10.3958 -1.553787 -1.28 - 22.29xao 263.50 - 5.7902 0.865487 -0.20 3.47
30wt%GLado -249.84 6.1131 -0.921437 -1.36 26.07guo - 31.23 0.8341 -0.121351 -4.06 -30.08xao 338.91 -7.2938 1.088319 -1.48 7.43
40wt%GLado 2.31 0.5215 -0.088593 -1.09 29.51guo -299.08 7.0773 -1.060392 -4.19 -18.13xao 254.90 - 5.4526 0.814575 -1.38 4.88
50wt%GLado - 190.56 4.8372 -0.732519 - 2.07 29.81guo 81.98 -1.3092 0.187596 -4.53 --8.61xao 241.72 -5.1344 0.766283 -2.37 7.22
60wt%GLado 329.11 -6.7493 -0.994969 -1.39 33.54guo -176.81 4.1708 -0.622878 -5.27 -25.22xao 298.50 -6.4189 0.958169 -2.62 5.84
70wt%GLado -40.23 1.6067 -0.254341 -3.28 39.76guo 25.68 -0.4721 0.072550 -7.35 - 27.81xao 378.29 8.1745 1.219061 - 3..71 10.13
known dipole values for other nucleosides andtheir corresponding base units are very close. Wethen eliminated D. G~l.cay' D. G~l.dip. D. G\l, ind andD. G\I,disP (Table 3) from D. G:) and the resultingD. G\l,HH H is the hydrophilic-hydrophobic hydra-tion effe~t which arises due to hydration of the hy-
drophobic and hydrophilic sites of the solutes inthe cosolvents as compared to that in water. Fi-gure 3 illustrates the D. G? H H H-composition pro-files in UH-water (solid line~) band GL-water (bro-ken lines) mixtures respectively, It may be notedthat uncertainties in diameter, dipole moment and
GANGULY et al.: TRANSFER ENERGETICS OF SOME NUCLEOSIDES 275
10,Xao(Gl)
_-<:s-::- Ado(GL).J:l-:::---
9:--=::8:~"";= -f)... ts--Guo{GL)
:-t~:~~:~~:-~----r-----------------1- 0~6f/?l~.....A::'1 -=- --=-=-=-=-=8=------:..-_-:::8:-AdOIGL)
---II ~~~~~ ·Xao(GL)
~(J.Q.-o-~ ····--t..--GUOIGLlGuo(UH)Xao(UH)
'-oE2
o
-.oK
:E -10..:I!I<I
o 20 30mol .,. cosol •• nt
-20
10
-300~--~1~0---~20~--~3~0---4~0~------~1101". cosolvlflt
Fig.2-Yariation of ~ G~).inl for various nucIeosides with mol% of UH (-) and GL (----) at 25°C
polarizability of the solute and solvent moleculesto the order of ±0.01 unit induce ±0.1 kJ mol-Iin ~ G?, cav and ~ G?, dip values, while lessthan ± 0.1 kJ mol- I in ~ G?, ind and ~ G?, disp va-lues. So the possible uncertainties of this orderwill hardly effect the nature of Il. G\l H H H-
composition profiles. ' I b
As indicated earlier6•lOc,1l.21, aqueous UH isboth hydrophobic and hydrophilic hydration redu-cer. From the structural consideration of the threenucleosides ado, guo and xao (vide Fig. 1), itshould be noted that the hydrophobic sites andhydrophilic sites increase in the relative orderxao ""guo < ado and ado < guo < xao respectively.Moreover, as observed elsewhere I, UH can formHe-bonds with carbonyl and imino parts of nucle-osides, termed as hydrophilic-hydrophilic groupinteraction. Therefore, hydrophilic hydration forthe nucleosides in aqueous UH will increase in therelative order xao <guo < ado since the number ofhydrophilic sites in the nucleosides increase in thereverse order i.e. ado <guo <xao [vide Fig. l(a-c)].Furthermore, since hydrophilic hydration is alsoguided by the acidity and basicity of the soluteand solvent, the above mentioned order for hydro-philic hydration for the nucleosides holds truesince p K; for ado, guo and xao in water are - 12,- 9 and - 6 respectively". Although the absolutevalues of pKa's of the nucleosides in these solventsare likely to alter, their relative hydrophilic hydra-tion of the solutes is not. So the order of relativehydrophilic hydration of the solutes is not likely tobe affected. Interestingly enough, the overall mag-nitude of ~ G\l, H,HbH for nucleosides is much
Xao(UH)
40
r, 30~
10
Oc------=~~---~~~--~~~---~40mol •••cosolwnt
Fig. 3--Yariation of ~ G? H H H of various nucIeosides withmol % of UH (':"j kd GL (----) at 25°C
smaller relative to that for the nucleic acid bases"This significant difference is due to the presenceof the furanose ring in the nucleosides which con-tains a number of hydrophobic as well as hydro-philic sites.
Similar to aqueous UH, aqueous GL is also hy-drophobic hydration reducer6•lOc,II,23. Further, asper relative order of hydrophobic sites of the nu-cleosides mentioned above, the hydrophobic hy-dration effect will be almost same for guo and xaoand slightly more in ado. But aqueous GL beingmore acidic as compared to water", hydrophilichydration for the nucleosides will be more in
Tabl
e3-
Val
ues
offr
eeen
ergi
esan
den
thal
pies
ofca
vity
form
atio
n(G
ean
dHe
),st
anda
rdfr
eeen
ergi
esof
tran.
••fer
[~G
o,.c
ay(i)
,.1
G~.
dip(
i),N -..
J.1
G~..
Ji),
.1G
~.di"
,(i),
.1G
~.HIH
H(i)
]and
entro
pies
oftra
nsfe
r[T
.1So
"cay
(i),T
.1S~
.dip(
i),T.
1S~.i
od(i)
,1t:.
S?di
",(i)
,:mSr
H1H
bH(i)
]ofad
o,gu
oan
dxa
o0'
1
~om
wat
erto
aque
ous
UH
and
GL
at.2
5°(u
nits
:k.
Jmol
-Ia
ndm
ole
frac
tion
scal
e)
Com
po:
lie.1
G?C
Oy(
i).1
G~.d
ip(i)
.1G
~.iod
(i).1
G~.d
i",(i
).1
G~.H
1HbH
(i)T.1
Sf.c
ov(i)
T.1S
~.di
p(i)
T.1S
:'.ind
(i)TA
SI.d
i~P(
i)TA
S:'.H
IHbH
Solv
ent
Solv
ent
A5.
00w
t%
UH
,a=
620
xlO
-fiK-';
M,=
18.6
7p,
-1.0
170
kgdm
?ad
o13
1.0
55.0
3.8
-2.3
-1.5
-1.2
1.2
·32.
5-4
.5-0
.3-0
.3-1
0.6
guo
140.
959
.24.
2-6
.6-1
.7-1
.14.
234
.9-1
1.9
-0.3
-0.3
-29.
1xa
o14
0.9
59.2
4.2
-8.4
-1.8
-1.0
4.5
34.9
-13.
5-0
.3-0
.3-3
.911
.52
wt%
UH
;a-
531
x1O
-6K
-';M
,-19.
60;p
.=1.
0285
kgdm
-3A
ado
132.
248
.54.
9-5
.6-1
.9-1
.74.
124
.9-7
.1-0
.4-0
.4P
guo
141.
952
.15.
1-1
4.2
-2.1
-1.6
11.0
26.9
-16.
9-0
.4-0
.4-1
7.9
xao
141.
952
.15.
1-1
7.0
-2.2
-1.5
1l.2
26.9
-20.
2-0
.4-0
.420
.5A
Z15
.00
wt%
UH
;a-
442
x1O
-6K
-I;
M,=
20.2
3;p,
=1.
0459
kgdm
"?
ado
135.
842
.38.
4-7
.6-3
.1-2
.54.
315
.0-1
0.0
-0.4
-0.4
18.4
S2 :>gu
o14
5.9
45.5
9.0
-19.
4-3
.4-2
.413
.916
.2-2
3.2
-0.4
-'0.4
-10.
2Z ....
xao
145.
945
.59.
0-2
2.8
-3.5
-2.3
14.5
16.2
-27.
2-0
.5-0
.433
.9o
A:t
20.3
1w
t%U
H;
a=43
5x
lO-'K
-I;
M,=
21.0
1;p,
=1.
0525
kgdm
-3tT1
ado
136.
142
.48.
6-1
0.6
-3.3
-2.9
6.8
15.1
-12.
2-0
.5-0
.530
.8.~
146.
29.
2-2
5.3
CIl
guo
45.6
-3.8
-2.8
19.8
16.3
-29.
1-0
.6-0
.5-1
0.9
tT114
6.2
45.6
9.2
-30.
2-3
.9-2
.721
.316
.3-3
4.7
-0.6
-0.5
38.8
~xa
o}»
A25
.00
wt%
UH
;a-
398
x1O
-'K-1
;M
,=21
.84;
p,-1
.062
2kg
dm-3
:>ad
o13
7.3
39.8
9.8
-12.
6-4
.1-3
.48.
811
.0-1
5.0
-0.6
-0.6
29.5
;8gu
o14
7.5
42.8
10.5
-31.
1-4
.6-3
.324
.911
.9-3
4.5
-0.7
-0.5
5.7
t= ...xa
o14
7.5
42.8
10.5
-32.
8-4
.7-3
.224
.011
.9-4
5.1
-0.7
-0.5
56.8
10 10A
0'1
29.6
4w
tUH
;a=
390
xlO
-fiK-I
;M
,""2
2.74
;p,-1
.079
Okg
dm"?
ado
140.
841
.013
.2-1
5.5
-4.8
-4.1
8.9
9.1
-17.
6-0
.7-0
.729
.8gu
o15
1.2
.t1.0
14.1
-37.
1-5
.5-3
.928
.39.
9-4
2.1
-0.8
-0.6
23.5
xao
151.
244
.114
.1-4
4.2
-5.6
-3.6
32.4
9.9
-50.
2-0
.8-0
.670
.1A
35.0
0wt
%U
H;
a-37
0x1O
-6K
-';M
,-23
.87;
p,-1
.090
6kg
dm?
ado
141.
140
.213
.4-1
7.9
-5.4
-4.6
11.9
7.6
-19.
4-0
.7-0
.728
.4gu
o15
1.7
43.3
14.5
-44.
0-5
.7-4
.434
.28.
2-4
9.2
-0.8
-0.6
18.0
xao
151.
743
.314
.5-5
1.5
-5.8
-4.2
40.0
8.2
-57.
6-0
.8-0
.679
.3A
36.8
3w
t%U
H;
a-36
1x
1O-6
K-I
;M.-2
4.29
;p,-1
.097
7kg
dm"?
ado
144.
640
.316
.9-1
9.3
-6.0
-5.0
10.1
4.7
-21.
7-0
.8-0
.730
.0gu
o15
5.3
43.3
18.1
-46.
2-6
.7-4
.033
.25.
1-5
1.9
-0.9
-0.7
20.1
xao
155.
343
.318
.1-5
5.0
-6.9
-4.6
40.8
5.1
-61.
8-0
.9-0
.787
.5
Con
td.
Tabl
:3-
:-Val
~01
'.frc
:c:~
ertP
e~~d
enlh
alp~
cl>
o~'c
avity
"or.l
Ila~:
oll(
.G<.~I
~"n)
:l>
~~d!
,d~r
~cl
I~rt:
i~o~
'tr~
IIiI'
crl~
(i"•
.m(i)
.A
Gl'.••
•••(i).
AG
•.•••
•(I).
AG
•.•••.,
.(I).
AU
r,H
.HH(
I)]an
dem
ropi
es01
trans
fer
PAS
•.••
•(1).
lAS
t.di
p(I)
.lAS
•. i••
•(I).
l2U
•. di",
(I).
~SI.H
IH~H
(I)]
ofad
o.au
oan
duo
trom
wat
erto
aque
ous
UH
and
GL
at25
°(u
nits
:kJ
mol
"1an
dm
ole
frac
tion
scal
e)_C
ontd
.
Com
pa.
i(A
G:'
.••,(i
)A
G?d
,p(i)
AG
:'.II,
d(i)
AG
:'.d,
,\.(i)
AC
i:'.I I" b,
,(i)
TAS
:'.••
•(i)
TAS
:'.di
l,(i)
TA"':
'.••
•d(i)
T4S
Y."i
~p(i)
'fA\.•
••
•.l ll
b"
Solv
ent
Solv
ent
B5
wt
%G
L,a-
310
x1O
-6K
- ';M
,=18
.78;
p,=
1.01
03kg
dm":
'ad
o12
7.5
26.5
0.2
-0.2
-0.1
-1.2
1.0
7.5
-0.1
0.0
-0.1
13.2
guo
136.
928
.50.
1-0
.5-0
.2-1
.01.
38.
2-1
.00.
0-0
.1-1
3.2
oxa
o13
6.9
28.5
0.1
-0.5
-0.2
-0.9
1.5
8.2
-0.5
0.0
-0.1
-6.7
> ZB
o10
WI%
GL;
a=34
5x
1O-6
K- '•
M,=
19.5
9;p,
-1.0
207
kgdm
"?
~ad
o12
7.3
29.8
-0.1
-0.1
-0.1
-2.1
1.9
11.0
-0.1
0.0
-0.2
15.2
guo
136.
732
.1-0
.2-0
.2-0
.3-2
.01.
912
.0-0
.80.
0-0
.2-1
7.8
."..•13
6.7
32.1
-0.2
-0.2
-0.3
r::oxa
o-1
.92.
512
.0-0
.30.
0-0
.2-1
1.4
::-B
~20
wt
%G
L;a=
378
x1O
-6K
- ';M
,=21
.48;
p,=
1.05
07kg
dm?
ado
127.
633
.80.
1-0
.1-0
.3-4
.35.
214
.7-0
.1-0
.1-0
.39.
8Z
guo
137.
136
.40.
1-0
.2-0
.6-3
.32.
515
.9-0
.6-0
.1-0
.4-3
7.1
CIl ~
xao
137.
136
.40.
1-0
.3-0
.6-3
.33.
915
.9-0
.3-0
.1-0
.4-1
1.6
:xlB
rn30
wt
%G
L;a
=39
8x
1O-6
K-';
M,=
23.7
5;p,
=1.
0706
kgdm
?Z
ado
125.
335
.8-2
.4-0
.1-0
.3-6
.27.
619
.5-0
.1-0
.1-0
.97.
7tT
1
guo
134.
538
.5-2
.7-0
.2-0
.7-5
.95.
421
.1-0
.4-0
.1-0
.8-4
9.9
~ tT1
xao
134.
538
.5-2
.7-0
.3-0
.8-5
.78.
021
.0-0
.4-0
.1-0
.8-1
2.4
~.
Bo
40w
t%
GL
a=46
4x
1O-6
K-';
M;=
26.5
7;Ps
=1.
1003
kgdm
-JCI
l
ado
125.
443
.2-2
.50.
1-0
.3-8
.410
.026
.30.
0-0
.2-1
.54.
90 '!1
guo
134.
046
.5-2
.80.
3-0
.7-7
.56.
528
.5-0
.1-0
.2-1
.6-4
4.7
CIl 0
xao
134.
646
.5.
'-2.8
0.3
-0.8
-7.2
9.1
28.5
-0.1
-0.2
-1.5
-21.
8~
B50
wt
%G
L;a=
497
x1O
-6K
-';M
,=30
.14;
p,=
1.12
39kg
dm"?
Zad
o12
3.4
46.9
-4.9
0.2
-c-0
.3-9
.912
.8.3
3.1
0.1
-0.2
-2.0
-1.2
c: I"')
guo
132.
450
.5-5
.30.
5-0
.9-9
.410
.635
.70.
1-0
.3-1
.9-4
2.2
r ['T1
xao
132.
450
.5-5
.30.
5-1
.1-9
.112
.635
.70.
3-0
.3-1
.8-2
6.7
0 CIl
B8
60w
t%
GL;
a=49
9x
1O-6
K- ';
M,=
34.8
3;p,
=1.
1526
kgdm
-J['T
1ad
o12
1.9
48.4
-6.6
0.4
-0.3
-11.
216
.335
.00.
5-0
.2-2
.30.
5V
l
guo
130.
952
.1-7
.10.
7-0
.3-1
0.6
12.0
37.8
-1.5
-0.3
-2.1
-62.
1xa
o13
0.9
52.1
-7.1
0.8
-0.6
-10.
314
.637
.81.
6-0
.3-2
.1-3
1.4
B70
wt
%G
L;a=
478
x1O
-6K
-';Z
M,=
41.2
4;p,
=1.
1784
kgdm
?ad
o11
9.4
47.1
-9.4
1.2
0.1
-11.
816
.637
.81.
1-0
.2-2
.63.
7gu
o12
8.1
50.6
-10
.22.
8-0
.7-1
1.2
11.9
40.7
2.5
-0.3
-2.4
-68.
3xa
o12
8.1
50.6
-10.
23.
4-0
.9-1
0.9
14.9
40.7
3.0
-0.4
-2.4
-30.
8tv
icon
td)
--..J
--..J
278
~-
~"~
<3
'1(:j-<3
-c."".:
\:l<3
~"
'6"<3
c11;»'0en
'1:1::'
a;..I
§~~'b'b'b'b,-.,.,~~oo-a-e V...-.j-ooooo.....;v)oOv)v)~.-I NNNXo~
N -c ;::; .,., .,., 00 0 N N N
~ 00 0 N .-...: ,.,.; -<i- -a 01 ~ 00 00N N N
s~'0en o ::t: ....l 0 0 0<,
C :i;:J 0 "0 :s '"'" 0() ><U;»'0en
INDIAN J CHEM, SEe. A, APRIL 1996
aqueous GL. In other words, hydrophilic hydra-tion will oppose hydrophobic hydration effect inGl.-water mixtures. And that is why we find6. G~ H H H in the case of aqueous GL to be lessthan' aq~eous UH. Moreover, as the intensity ofhydrophilic sites in the nucleosides increase in therelative order ado < guo < xao, the nucleosidesshould undergo hydrophilic hydration in aqueousGL following the same order. Since the p K; va-lues and hence the basicity of the nucleosides inwater and in other solvents, are in the orderxao <guo < ado, it is expected that hydrophilic hy-dration as induced by acidity of the solvents andbasicity of the solutes will also be in the same or-der. Therefore, in the case of Gl.-water mixtures,it appears that hydrophilic hydration is a combina-tion of these two effects, which together with theeffect of hydrophobic hydration accounts for the6. G?-composition profiles of the type as shown inFig. 3 {broken lines}.
Entropies of transferFigures 4 (inset) and 5 {solid lines} show the
T6.S?-composition profiles for ado, guo and xaoin UH-water and GL-water mixtures respectively.The observed T6. S?-composition profiles of thenucleosides though somewhat complex and diffi-cult to understand, the normalised T6. S? H H H {1}-
composition profiles (vide Figs 4 and 5) indi~ate aregular order and hence easier to understand. So,the complex nature of the T6. S?{i)-compositionprofiles are not quite unusual because of theadded complexities arising from the effect ofstructural changes of the solvents induced by thespecies, particularly on the H,HbH-effect. So, nodefinite conclusion should be drawn from them
100
40~------------~
10•••••• UN
20
-400:------:';,O:------:20~~
_''''UNFig. 4-Variation of T~Sainset) and T~S? HH H for various
. .I bnucIeosides with % UH at 25°C
GANGULY et al.: TRANSFER ENERGETICS OF SOME NUCLEOSIDES
40 Ado
";1 20
~<,:z:~ 0:r:...~.- -20••
__'O'-::....,,--o-------r.....--~~ Xoo
•..1/1<I~ -40
tJ.--- Guocr------~-- Xoo
-10
-.0~---~1~0~----~2~0----~3~0-------~mol.". GL
Fig: S-Variation of Tts S", (-) and TilS~l.HlH H (---) of variousnucIeosides with mol % GL at t'soC
unless the various interaction effects be excludedfrom ~ S\l(i). We, therefore, computed the hydro-philic-hydrophobic hydration effect, tl.S?, HIHb(i) byeliminating as before", the transfer entropies dueto cavity formation (~S?, caJ, dipole-dipole(~S~. dip), dipole-induced dipole (~Sil. ind) and dis-persion (~Sv, disp) interactions from ~ Sil. Figures 4and 5 (broken lines) depict the variation of.T~ SiloHIHhHwith composition for ado, guo and xaoIII Ul-l-water and GL-water mixtures respectively.As in the case of ~ Gil values, uncertainties of± 0.01 unit in diameters, dipole moment and po-larizability of solute and solvent molecules induceuncertainties of the order of ± 0.1 kJ mol- I forT~ S? cav and T~ S~.dip values, whereas less than± 0.01 kJ mol- I in the dispersion and dipole-in-duced dipole interaction effects, which are negligi-bly small as compared to the observed magnitudesof the respective effects. So; the possible uncer-tainties hardly alter the nature of theT~ S~,HIHhH(i)-composition profiles. A erusal ofthe relative magnitudes of different interaction ef-fects of T~ S~ (vide Table 3) reveals that the op-posing magnitudes of cavity and dipole interactioneffects, as well as T~ Si)HH H effect result in the
, I bobserved ups and downs of T~ S\l-compositionprofiles. Evidently understanding of theT~ S~,HIH~Heffect should be of particular interest.
As indicated in our previous papers6,lOc.24, theentropy change due to HIHbH effect can beascribed as
... (5)
279
where tl. sy is defined as the entropy change asso-ciated with the dismantling of the hydrationsheath, ~ S~ that due to formation of 3D normalwater structure released from step 1. ~ S~ is as-sociated with the disruption of the structure of themixed solvents and ~ S~ is the entropy change forhydrophobic/hydrophilic hydration of the solutesin the mixed solvents.
For the three nucleosides used for the presentstudy in aqueous UH and aqueous GL, ~ S'l dueto hydrophilic hydration (HIH i.e. the entropychange accompanying the break down of the hy-dration sphere round the hydrophilic sites of thesolutes is a small positive quantity. But ~ S~ dueto HIH is largely negative due to the formation ofthree dimensional (3D) ice-like water structure outof the released disordered water molecules. Onthe other hand, ~ Sjl due to hydrophobic hydra-tion (HhH) should be zero since no disorder is tobe made for the dismantling of hydration sphere,induced by hydrophobic hydration. But ~ S~ dueto HbH is a positive quantity, as the systemchanges from a more ordered state (1) to a lessordered state (2). Therefore, (~S\l + ~ S~) due toHIHbH effect for a particular nucleoside is a con-stant quantity as it is related to water moleculesand will be either positive or negative dependingon the relative predominance of the hydrophilicand hydrophobic sites in the nucleoside. And, asindicated earlier, from the relative order of the hy-drophobic hydrophilic sites in the nucleosides itfollows that in the case of ado, (~S7 +~ S~) dueto HIHbH effect will be a small positive quantitywhereas the same for guo and xao will be negativein magnitude.
Figure 4 shows the T~ Sil,HH H-compositionprofiles in UH-water mixtures. ~hS~ is initiallyzero as aqueous UH is a 3D structure break-er24b,25but positive at higher compositions due tothe formation of VH + H20 aggregates 14h,25,~ S~ ,that due to entropy change for hydrophobic/hy-drophilic hydration of the solutes in the mixed sol-vents is a small negative quantity since aqueousVH is a hydrophobic as well as a hydrophilic hy-dration reducer. Therefore, on combining(~S~ +~ S~) with (~S'i + ~ sg) a downwardtrend is initially observed in the T~ S~ HH H-composition profiles. In the intermediate reki~n,however, the increase in T~ Sil.HH H is attributableto the increasingly positive (~Sf +~ S~) causedby the formation of VH + H20 aggregates and thedecrease in HIHbH effect relative to water. Athigher compositions, the downward trend indi-cates the effect of packing imbalance. Figure 5(broken lines), illustrates the 1'!1S~.HIHhH-
280 INDIAN J CHEM, SEC. A, APRIL 1996
composition profiles for the nucleosides in GL-wa-ter mixtures. As indicated earlier'!", ~ So is slightlypositive initially and then zero at further highercomposition, ~ S~, which is an amalgamation ofthe opposite forces HbH and H1H, will be a smallnegative quantity. Thus on combining(~S~ + ~ S~ ) with (~S? + ~ S~ ) it is expected thatin the case of ado, the T~ S? HHbH-compositionprofiles should show an upward trend and thesame for guo and xao should pass through a mini-mum initially and then show the same upwardtrend in the intermediate region, as observed. Athigher composition however, all the curves movedownward due to the onset of packing imbalance.
To conclude, the transfer free energy-composi-tion profiles show an increasingly negative trend inboth UH-water and GL-water mixture indicatingthat the nyucleosides ado, guo and xao are moresolvated in the two cosolvent systems than in wa-ter. The extent of relative solvation of the nucleo-sides in the mixed solvents as compared to that inwater, can be considered as a criterion for guidingthe relative stability and denaturation of doublestranded nucleic acid helix. However, the ther-modynamic parameters especially ~ G~,HH H andT!1 S?, H\HH will help reflect in a much bette~ man-ner the effect of aqueous UH and GL on the rela-tive stability of nucleic acids. This is because thetwo strands of a DNA helix are not only held byH-bonds between complimentary base pairs butalso the strands themselves, composed of alter-nately linked ribose and phosphate groups, remainsolvated in water through H-bonding. Therefore,increased solvation of the nucleosides in the aque-ous UH and GL solvents will weaken the H-bondsformed between the bases. And this can accountfor the destabilization of the nucleic acid structureand the consequent denaturation of the strands.
~knowledgementThanks are due to UGC, New Delhi for finan-
aical assistance.
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