Indian Journal of ChemistryVol. 34A, November 1995, pp. 857-865

.Transfer energetics of uracil, thymine, cytosine and adenine in aqueousmixtures of lithium chloride, sodium chloride and potassium chloride

Sonali Ganguly & Kiron K Kundu"

Physical Chemistry Laboratories, Jadavpur University, Calcutta 700 032, India

Received 5 Apri11995; revised and accepted 27 June 1995

Standard free energies (~GV and entropies (~SV of transfer of nucleic acid bases viz. uracil (URA),thymine (lHY), cytosine (CYT) and adenine (ADE) from water to aqueous mixtures of lithium chlo-ride, sodium chloride and potassium chloride have been evaluated from solubility measurements at dif-ferent temperatures. The interaction effect of ~ G~ int, as guided by the combined effects of hydrophilichydration (HtH) of hydrophilic parts and hydrophobic hydration (HbH) of hydrophobic parts of thesebases in these ionic cosolvents relative to that in water, have been obtained by subtraction of the cavityeffect A G~,cav(i) as computed by SPT formulations from the corresponding A G~ values. The composi-tion profiles of A G~ and A G~ int indicate that each of the bases is found to be increasingly desolvated inthese aqueous electrolytes save URA and lHY at higher compositions of aqueous KCl, their order be-ing KCI <NaCI <LiCI at any of the compositions, as expected from the primary solvation effect of thecations of the ionic cosolvents. The observed T~ S~ and TA S~,int (i)-composition profiles are, however,found to be dictated by the relative 3D structure breaking effect as well as the relative HtHbH effect, in-duced by these ionic cosolvents. The observed increased desolvation of the bases reflect that the in-tramolecular H-bonds between the bases of the double strands of DNAIRNA helices are likely to getstrengthened in these ionic cosolvent systems.

There are several reports available in literaturewith regard to the denaturing effect of differentcosolvent systems, namely, aqueous ethanol' ,aqueous methanol', aqueous dimethylformamide',aqueous dimethylsulphoxide/, aqueous urea' andaqueous glycerol'> towards nucleic acid doublehelix. However, inspite of a large number of stud-ies on the interactions of nucleic acids and. theirmodel compounds with neutral salt, the exact na-ture of interactions taking place in aqueous saltsystems which led to the stabilization or denatura-tion of the nucleic acid helix is not very clear=".Consequently, the study of relative solvation be-haviour of DNA-RNA base units and nucleosidesin both ionic and non-ionic cosolvent systems isconsidered immensely useful 10. In two recent pa-persll,12 we have described the roles of aqueousurea and glycerol as nucleic acid denaturants asunderstood from the solvation behaviour of nuc-leic acid bases and nucleosides in these cosolventsystems. Furthermore, the results have been dis-cussed in terms of hydrophilic and hydrophobichydrations and in the case of transfer entropies interms of relative solvent structuredness as well. Inthe present paper, in order to understand the rela-tive stabilization of nucleic acid helix in electrolyte

solutions, the above studies have been extended todifferent compositions of aqueous salt solutionslike LiCl, NaCI and KCl and we present free ener-gies (6. G~) and entropies of transfer (6.S~) at 25°Cfor nucleic acid bases viz. uracil (URA), thymine(THY), cytosine (CYT) and adenine (ADE) as ob-tained from solubility measurements at differenttemperatures in water and in a series of aqueousmixtures of 0.1, 0.5, 1.0 and 2.0 m electrolytes.After elimination of the effect due to cavity forma-tion, the results have been discussed in terms ofhydrophilic-hydrophobic hydration (H1HbH) effectas induced by the salts in these ionic cosolventsystems relative to that in water.

Material and MethodsLiCI (grade 0505, Sigma), NaCI (GR, E. Merck)

and KCI (GR, E. Merck) were thoroughly dried ina vacuum desiccator before use. URA, THY, CYTand ADE (Sigma) were used as supplied. Theirpurity as checked by UV spectroscopy was foundto lie within 98-99%. The solvents of various mo-lalities (0.1, 0'5, 1.0 and 2.0 m) for LiCl, NaCIand KCI solutions were prepared by mixing thecomponents by weight. Water used was triply dis-tilled and CO2 free. The method adopted for the

858 INDIAN J CHEM. SEe. A, NOVEMBER 1995

measurements. of saturated solubilities at eachtemperature was the same as described'! previous-ly. Aliquots of each of the saturated solutionswere withdrawn at 2-day intervals, properly dilut-ed with water in order to restrict the absorbancevalue around 0.8 and the optical absorbances ofthe diluted solutions were measured with a.PerkinElmer Lamda 34 IN spectrophotometer. The re-quired A IIIIU and molar extinction coefficient valuesused were taken from the literature I3. Saturationwas generally attained within 7-8 days after whichthe measured concentration of the solutionsshowed no change beyond the experimental uncer-tainty of ± 1%. The measurements were made atfiv= equidistant temperature ranging from 15 to3S-c. .

Results and DiscussionThe solubilities (S) in mol dm - 3 of various nuc-

leic acid bases at different temperatures in water,LiCI-water, NaCI-water and KCI-water mixturesare given in Table 1.

Assuming the degree of ionization of these bio-molecules to bezero in water and mixed solventsand the effect of activity coefficient factor to benegligibly small" because of fairly low solubility ofthese non-electrolytes in each of the solvents caus-ing the activity coefficients to be more or less un-ity, the free energy of solutions (~G~) of eachsolute was computed on the molar scale by therelation

~G~= -RTln S ... (1)

The values in each solvent at different tempera-tures were fitted by the method of least squares toan equation of the form

~G~=a+bT+cTln T ... (2)

where T is the absolute temperature. The valuesof the coefficients a, b and c are presented inTable 2. These reproduce the experimental data towithin ± 0.03 klmol" I. The standard free energiesof transfer ~ G~of the solutes uracil, thymine, cyt-osine and adenine from water (w) to the mixedsolvents (s) were computed at 25°C on mole frac-tion scale (N) using relation

~ G~,N(i)=- RTln Ss/Sw - RTln M, pwl MwPs... (3)

= (as - aJ+ ib, - bw) T+ (CS - cw)TIn T

... (4)

hi Eq. (4) Mdenotes molar mass, T=298.15K,density in kg dm - 3. The corresponding standardentropies of transfer were computed from Eq. 5

~ S~' N(i)= (bw - bs) + (c, - cs)(1+ In T)

- R In M. Pwl MsPs + RT( as - aw)' •• (5)

where aw= -dlnpwldT and as= -dlnp/dTstand for coefficient of thermal expansion of waterand cosolvents respectively. The required valuesof P at different temperatures were taken from theliterature IS and the values of a were computed

Table I-Solubilities (S in mol dm-3) of URA, THY, CYT and ADE in water and aqueous LiCl, NaCI and KO at differenttemperatures

Compound 15 20 25 30 35°C

WaterURA 0.0170 0.0209 0.0261 0.0313 0.0388THY 0.0207 0.0'234 0.0277 0.0334 0.0456CYT 0.0479 0.0550 0.0682 0.0908 0.1406ADE 0.0111 0.0142 0.0171 0.0185 0.0197

0.1 mLiOURA 0:0158 0.0206 0.0247 0.0287 0.0327THY 0.0197 0.0228 0.0258 0.0302 0.0336CYT 0.0350 0.0440 0.0534 0.0643 0.0734ADE 0.0101 0.01283 0.01603 0.0190 0.0220

0.5 mLiOURA 0.0142 0.0191 0.0227 0.0272 0.0305THY 0.0165 0.0212 0.0231 0.0242 0.0254CYT 0.0346 0.0435 0.0516 0.0628 0.0728

ADE 0.0081 0.0101 0.0140 0.0168 0.0192

-(Conld)

GANGULY et aL: TRANSFER ENERGETICS OF NUCLEIC ACID BASES IN AQ. SALT SOumONS 859

Table I-Solubilities (Sin mol dm-3) ofURA, THY, CYT and ADE in water and aqueous LiCI, NaCI and KO at differenttemperatures-{ ConJd)

Compound 15 25 30 35°C1.0 mLiO

URA 0.0147 0.01953 0.0230 0.0276 0.0310THY 0.0148 0.01901 0.0215 0.0238 0.0257CYT 0.0395 0.0509 0.0615 0.0705 0.0780ADE 0.0070 0.0096 0.0128 0.0168 0.0191

2.0 mLiOURA 0.0182 0.0220 0.0256 0.0302 0.0444THY 0.0140 0.0174 0.0205 0.0246 0.0284CYT 0.0470 0.0584 0.0674 0.0756 0.0831ADE 0.0050 0.0075 0.0108 0~0138 0.0156

0.1 mNaOURA 0.0163 0.0210 0.0254 0.0291 0.0303THY 0.0205 0.0236 0.0261 0.0285 0.0311CYT 0.0390 0.0492 0.0584 0.0677 0.0761ADE 0.0107 0.0135 0.0155 0.0179 0.0202

0.5 mNaOURA 0.0148 0.0196 0.0241 0.027 0.0302THY 0.0192 0.0238 0.0251 0.0279 0.0304CYT 0.0404 0.0507 0.0597 0.0701 0.0767ADE 0.0095 0.0120 0.0152 0.0170 0.0176

1.0 mNaOURA 0.0151 0.0199 0.0243 0.0277 0.0306THY 0.0167 0.0213 0.0230 0.0262 0.0297CYT 0.0408 0.0512 0.0610 0.0706 0.0772ADE 0.0092 0.0118 0.0145 0.0161 0.0174

2.0mNaOURA 0.0195 0.0240 0.0283 0.0330 0.0371THY 0.0158 0.0192 0.0219 0.0281 -0.0308CYT 0.0389 0.0491 0.0580 0.0673 0.0747ADE 0.0034 0.0077 0.0124 0.0130 0.0160

0.1 mKOURA 0.0166 0.0218 0.0258 0.0290 0.0318THY 0.0210 0.0252 0.0280 0.0314 0.0324CYT 0.0358 0.0599 0.0645 0.0768 0.0874ADE 0.0107 0.0142 0.0167 0.0190 0.0210

0.5mKOURA 0.0174 0.0220 0.0264 0.0292 0.0320THY 0.0216 0.0258 0.0284 0.0319 0.0331CYT 0.0376 0.0529 0.0682 0.0815 0.0919ADE 0.0110 0:0145 0.0169 0.0192 0.0213

1.0mKOURA 0.0140 0.0200 0.0286 0.0296 0.0318THY 0.0232 0.0270 0.0295 0.0333 0.0361CYT 0.0465 0.0623 0.0755 0.0901 0.1020ADE 0.0105 0.0138 0.0163 0.0186 0.0206

2.0mKOURA 0.0398 0.0450 0.0489 0.0528 0.0562·THY 0.0337 0.0378 • 0.0402 0.0429 0.0446CYT 0.0603 0.0718 0.0821 0.0917 0.1021ADE 0.0093 0.0128 0.0154 0.0175 0.0197

860 INDIAN J CHEM. SEe. A, NOVEMBER 1995

------Table 2-Coefficients a, b, cand transfer energetics (A G?and TAS~inkJmol-.t)ofURA, THY, CYT and ADE from water to

aqueous mixtures of LiCl, NaCI and KCI at 25°C (mole fraction scale)

Compound a b c dG~ TdS~klmol" ' kJmol-1K-1 kJmol-1 K-I

WaterURA -5.20 0.7274 -0.119260THY -530.41 12.4964 -1.875789CYT -883.32 20.6227 - 3.095658ADE 574.60 -12.4805 1.858190

0.1 mLiCIURA 377.81 -7.9307 1.174'940 0.11 -2.96THY 32.67 -0.3219 0.042593 0.14 -9.00CYT 259.88 -5.2022 0.764342 0.64 -8.29ADE 337.745 -7.0193s 1.039.266 0.25 7.09

0.5 mUCIURA 416.20s -8.7905 1.303341 0.27 -3.01THY 582.99 -12.6829 1.888311 0.41 -9.28CYT 273.80 -5.5451 0.816342 0.66 -9.90ADE 483.59 -10.2256 1.516306 0.51 10.41

1.0 mLiCIURA 367.30 -7.7043 1.141489 0.27 -3.62THY 435.91s -9.3898 1.397046 0.64s -10.07CYT 397.80 -8.3894 1.242342 0.29 -12.55ADE 464.41 -9:6755 1.431120 0.64 16.54

2.0mLiCIURA -480.82 11.3362 -1.701260 -0.02 -3.93

THY 132.68 -2.4513 0.357780 0.70 -12.38CYT 313.18 -6.6645 0.986342 0.07 -15.62

ADE 819.37 -17.5622 2.606683 1.14 20.51

0.1 mNaCiURA 592.44 -12.7691 1.897740 0.02 -3.74

THY 159.49 - 3.i!150 0.475711 0.13 -11.33

CYT 339.03 -7.01815 1.036342 0.42 -10.02

ADE 492.60 -10.6649 1.587914 0.19 -1.59

0.5 mNaCiURA 533.60 -11.4656 1.703714 0.21 -4.90

THY 255.46 -5.3854 0.800,211 0.24 -12.22

CYT 372.68 -7.8149 1.156342 0.37 -12.10

ADE 497.80 -10.7801 1.605114 0.27 -1.61

1.0 mNaCI

URA 497.96 -10.6667 1.584454 0.17 -4.93sTHY 250.79 -5.2842 0.785~11 0.47 -12.83

CYT 358.63 -7.5863 1.124451 0.32s -16.53

ADE 540.10 -11.7285 1.746732 0.37 -1.60

2.0,mNaCi

URA 211.48 -4.2708 0.630.289 0.08 -7.13

THY 184.49 -3.8187 0.567211 0.60 -14.05

CYT 442.73 -9.4876 1.408342 0.47 -16.21

ADE 1360.58 -30.1500 4.497196 0.85 -1.58

Conlll.

GANGULY et al: TRANSFER ENERGETICS OF NUCLEIC'ACID BASES IN AQ. SALT SOLUTIONS 861

Table 2-Coefficients a, b, cand transfer energetics (6 G~and T6S?in kJmol I) ofURA, THY, CYT and ADE from water toaqueous mixtures of LiCI, NaCI and KCl at 25°C (mole fraction scale)-( COlt/d)

Compound a b c 6 G:) T6 S~kJmol-1 kJmol-1K-1 kJmol-1K-1

0.1 mKCIURA 488.05 -10.4882 1.558'899 0.08 -7.13

THY 361.26 -7.7~27 1.158526 -0.03 -12.94

CYT 648.58 -14.00S5 2.080342 0.17 -11.50

ADE 481.12 -10.3160 1.533343 0.03 3.39

0.5 mKCIURA 443.575 - 9.5142 1.4141083 0.01 -8.35THY 315.34 -6.7553 1.005191 -0.10 -13.07CYT 596.78 -12.8665 1.910'842 0.02 -13.62

ADE 434.89 -9.2872 1.380009 0.08 2.83

1.0mKCIURA 550.40 -11.9909 1.7851740 -0.26 -12.10THY 199.19 -4.1896 0.623211 -0.18 -15.29CYT 442.73 -9.4876 1.408342 -0.22 -16.60ADE 460.98 -9.8599 1.465194 0.14 3.49

20mKCIURA 149.57 - 3.0974 0.460003 -1.54 -16.28THY 172.51 - 3.6579 0.545185 -0.835 -17.94CYT 181.61 -3.6943 0.545185 -0.30 -20.17ADE 493.22 -10.5498 1.567417 0.31 5.08

thereof and are furnished in Table 3. 6 G~ andT6 S~ vlues are given in Table 2. The standard de-viations in 6 G~ and /:1 S~ are ± 0.05 kJ mol- ,I and± 2 JK - I mol- 1 respectively.

Since the large sized purine and pyrimidinebases under present study possess both hydrophil-ic and hydrophobic parts, the solvation or interac-tion effect is likely to be guided by the combinedeffects of hydrophilic hydration (HIH) as well ashydrophobic hydration (HbH), tacitly referred toas HIHbH effect.

Since the standard free energies of transfer dueto interaction effect If" 6 G~.int is considered to bea better indicator of solute solvent interaction,particularly for large size moleculesll.15.16-18suchas these bases, first we tentatively calculate thecavity effect (6 G~.cavl based on scaled particletheory (SPT )19 and deduct it from 6 G~ to obtainvalues for 6 G? int' The values of 6 G? ca. and6 G? intso obtained are furnished in Table 3. Thecorresponding entropy data viz. 6 S? ca. and 6S?, int

were also computed in a similar manner and arepresented in Table 3. Figure l(a-d) shows the var-iation of 6 G~ and 6 G? int of URA, THY, CYTand ADE with mol % electrolyte. As reflectedfrom IJ. G~.int-composition profiles, in the aqueoussolutions of alkali metal chlorides, the observedorder of destabilization of all the nucleic acid

bases save URA and THY at higher compositionsof KCl, is K + < Na + < Li". Li+, being small in sizeand possessing spherical s-orbital, has an intenseforce field and hence a strong hydration cospherearound it. Therefore, hydrophobic-hydrophilic hy-dration of the nucleic acid bases in aqueous saltsolutions as compared to that in water will bemuch more reduced in LiCI than NaCl and KCl.Furthermore, to this effect is superimposed the ef-fect of interaction of the cations (Li+, Na +, K +)

and anion CI- with the formal negative and posi-tive charge centres of the solutes respectively.With smaller ion of the same charge electric forcefield is no doubt intense but the number of solutedipoles that can interact with this field is less,while with the larger ions although the force fieldis small the possibility of larger number of solutedipoles interacting is large and this gives rise tothe observed order of 6 G~.intas guided by Stokesradii.

Figure 2(a-d) illustrates T6 S~(i) and T~ S~.int

(i)-composition profiles of the bases in LiCl, NaCland KCl electrolyte solution. Interestingly, in allthe cases except for ADE, these profiles have in-creasingly downward trend which may be partly at-tributed to the well-known 3D structure breakingeffect of the electrolyte, as would be evident fromthe following discussion.

862 INDIAN J CHEM. SEe. A, NOVEMBER 1995

Table 3- Values of free energies and enthalpies of cavity formation (Gc and Hcl and. interaction free energies and eni!opls of transfer(6 G?, in' and T6 S?, in,) of URA, THY, CYT and ADE from water to aqoeous LiCI, NaCl, KCI at 25°C in kJ mol-1 .

6 G?, eev

(i)6G?, in'

(i)T6S?, cay,

(i)T6S?, in,·

(i)Compound

Water Solvent Water Solvent

0.1 m LiCI; btiCi =0.241 nm; a=265 X 106K-1; V,= 18.01 cm3mol-1

URA 37.0 37.0 5.2 6.3 0 0.11 1.1 -4.1THY 51.5 51.5 7.4 8.8 .0 0.14 1.4 -10.4CYT 44.4 44.4 6.3 7.6 D. 0.64 1.3 -9.6ADE 53.0 53.0 7.6 9.1 0 0.25 1.5 +5.6

0.5 m LiCl; a = 267 x 106K - '; V, = 18.05 cm'mol" 1

URA 36.8 6.3 -0.2 0.47 1.3 -4.3

THY 51.2 8.8 -0.2 0.61 1.6 -1.0.9

CYT 44.2 7.6 -.0.2 0.86 1.5 -11.4

ADE 52.8 9.1 -0.2 0.71 1.7 8.7

1.0 m LiCl; a= 283 x 106K-'; v,~18.07 cm-mol" '

URA 36.7 6.6 -0.3 0.57 1.7 -5.3

THY 51.1 9.3 -0.4 1.045 2.3 -12.4

CYT 44.1 8.0 -0.3 0.59 2.0 -14.6

ADE 52.7 9.6 -0.3 0.94 2.3 14.2

2.0 m LiCl; a = 323 x 166K - 1; V,= 18.16 em-mol" I.

URA 36.5 7.4 -0.5 0.48 2.7 -6.6

THY 51.0 10.5 -0.5 -0.20 3.6 -16.0

CYT 43.9 9.0 -0.5 0.57 3.2 -18.8

ADE 52.5 16.8 -0.5 ·1.64 3.7 16.80.1 m NaCl; bNaCi = 0.276 nm; a=278 x 1O-6K-I; V,= 18.02 cm3mol-1

URA 37.0 6.5 0 0.02 1.3 -5.0

THY 5.1.5 9.2 0 0.13 1.8 -13.1

CYT 44.4 7.9 0 0.42 1.6 -11.6

ADE 53.0 9.5 0 0.19 1.9 -3.5

0.5 m NaCI; a= 285 x 10" K - '; V,= 17.97 cmJmol-1

URA 37.0 6.7 0 0.21 -1.5 -6.4

THY 51.5 9.5 0 0.24 2.1 -14.3

CYT 44.4 8.1 0 0.37 1.8 -13.9

ADE 53.0 9.7 0 0.27 2.1 -3.7

1.0 m NaCI; a= 3.15 x IO-"K -I; V,= 17.88 cm)mol-'

URA 37.0 7.4 0 0.17 2.2 -7.1

THY 51.5 10.5 0 0.47 3.1 -15.9

CYT 44.4 8.9 0 0.325 2.6 -19.1

ADE 53.0 10.7 0 0.37 3.1 -4.7I

2.0 m NaC\; a = 375 x lO-hK -I; V, = 17.82 cm)mol-'

URA 37.0 8.7 0 0.08 3.5 -10.6

THY 51.5 12.4 0 0.60 5.0 -19.1

CYT 44.4 10.6 .0 .0.47 4.1 -20.3

ADE 53.0 12.8 .0 0.85 5 ..0 -6.6

0.1 m KCI; bKCI =0.314 nm; a= 284 x IO-"K - I; V, = 18.02 cnr'rnol "!

URA 37.0 6.8 0 0.08 1.6 -8.7

THY 51.5 9.4 .0 -0.03 2 ..0 -14.9

CYT 44.4 8.2 0 .0.17 1.9 -13.4

ADE 53.0 9.8 0 0.03 2.2 1.2

.-(Contd)

GANGULY et aL: TRANSFER ENERGETICS OF NUClEIC ACID BASES IN AQ. SALT SOumONS 863

Table 3- Values offree energies and enthalpies of cavity formation (Geand He) and interaction free energies and entropis of transfer(d G?, intand Td S?, int)of URA, TH'X, CYT and ADE from water to aqoeous LiCl, NaCl, KCl at 25°C in kJ mol-I-Contd

Compound Gc He d G? cav d G? int Td S? cev Td S? int(i) (i) (i) (i)

Water Solvent Water

0.5 mKCl; a=290 x 1O-6K-'; v,= 17.98 cm3mol-1

Solvent

URATHYC;YTADE

36.851.244.252.8

6.79.68.39.9

--'0.2-0.2,-0.2-0.2

0.210.100.220.28

-10.1-15.5-15.8

0.3

1.7

2.42.22.5

1.0 mKCl; a= 333 x 1O-6K-'; V,= 17.86 cmJmol-1

URA 36.7 7.8 -;-0.3 0.04 2.9 -15.0THY 51.1 10.9 -0.4 0.22 3.9 -19.2

CYT 44.1 9.4 ·-0.3 0.08 3.4 -20.0ADE 52.7 11.3 -0.3 0.44 4.0 -0.5

2.0 mKCl; a= 387 x 10-6K-"; v,= 17.77 cm3mol-'URA 36.5 8.9 -0.5 -1.04 4.2 -20.5THY 51.0 12.6 -0.5 -0.335 5.7 -23.6CYT 43.9 10.8 -0.5 0.20 5.0 -25.2ADE 52.5 12.9 -0.5 0.81 5.8 -0.7

Mol wt MUCI = 42.40; MNaa = 58.54; MKCI = 74.56.'References 15, 20

URA ilH

(0)0-5

LlCI -'i.•

NoCt ~

1-0-1••••• -I~ L.--+---:!_-±--+!~

Liel

NeCt

KCIt 2 3 4....""-"",..-,.()

_'.5L.-_.L.,---'-2 -~3 -~4~KCI

_01% .I.el.oe,t.

THY

,·0(b)

0·5'i

~ __ Liel

...~ 0G'..

-0·5

ItCI-'.()L.--~--!-2 --+3 -~4

1IOI'l.IItctt'ol,t.

Fig. l-(a,b) Variation of d G~)and d G?,int (inset) of (a) URA(b) THY with mol % electrolyte at 25°C

-~L--L--2~-.L.3---'--

••• ,.•• I.elro""

(c)

'j 1~ liCl

UCl ~ 0.5 tt.CI~----MCl ~. o~-u:::~;::::==::;:.KCt

1j -O.5L--+-~2i-~3~~4-..J

_""_""110

2 3_01% .I.ct.olytw

ADE . &,H

Cd)

LICI

NaCtKCI

Fig. l-(c,d) Variation of dG?and dG?'int (inset) of (c) CYTand (d) ADE with mol % electrolyte at 25°C

864 INDIAN J CHEM. SEe. A, NOVEMBER 1995

Following Kundu et al.'s four-step transfer

process 11.'4-'7

4

~S~.in!(i)= I ~S~ = ~S~ + ~S~n~'+ ~ S~ + ~ S~ i.e. ~ S~.in!(i) is assumed to involvethe ~ollowing four steps: (1) breakdown of the hy-dration cosphere around the nucleic acid baseswith an increase in entropy for hydrophilic hydra-tion (H,H) and without any change in entropy forhydrophobic hydration (HbH), (2) formation of'characteristic' 3D structure of water i.e. five watermolecules form a unit of 3D tetrahedral waterstructure with one water molecule at the centreand four others at the four corners of the tetrahe-dron H-bonded to the central water molecule witha decrease in entropy for H,H and increase in en-tropy for HbH, (3) disruption of relevant struc-tures of mixed solvent, if any, to solvate the trans-ferred solutes, with an increase in entropy and (4)hydrophilic/hydrophobic hydration of the solutesin the mixed solvents as well as interaction be-tween the cations and anions of the cosolventswith the solute dipoles. As indicatd in the case ofthe nucleosides in aqueous UH and GLmixtures '2, the overall value for (~SI!+~Sli) dueto H,HbH effect is a constant quantity as it is re-lated to water molecules and will be either positiveor negative depending on the relative predomin-ance of the hydrophilic and hydrophobic sites inthe solutes. The hydrophobic sites in the nucleic

URA

-;.. °ftll.:=F::::X::====-IE Ill: LiCI~ -10 HaCI

o.~-20'----t_-t-_-+_+KC_1 -Ii 1 2 3 4moI"IoNctrolyw

LICIHaCI

-20 ~;;--..L..--'-----li....-.-..L...,~

10

LICINelCI1((1

4

~OL---~--~2----~J----4~~IlOl% llectrolyte

Fig. 2-(a,b) Variation of TAS?and TAS~~inl(inset) of (a) URAand (b) THY with mol % electrolyte at 2SoC

acid bases increase in the order CYT <URA <THY <ADE and the hydrophilic sites increase inthe revese order. Thesefore, (~SI! + ~ S~) due toH,H effect (which is a positive quantity) will bemore for pyrimidine bases than ADE. So theoverall (~SI! + ~ S~) due to H,HbH effect will be asmall positive quantity for ADE since(~Sl + ~S~) due to H,H effect partially nullifiesthe positive (~S! + ~ Si) due to HbH effect.Whereas, in the case of URA, THY and CYT, thelarge negative magnitudes of (~SI! + ~ Sli) due toH,H effect combined with positive (~SI! + ~ S~)due to HbH effect gives rise to a net negative mag-nitude of (~ S! + ~ S~) due to H, HbH effect.

In the present LrCl-water, NaCl-water and KCI-water mixtures, the observed downward trend ofthe T~Si.int-composition profiles [Fig. 2(a-d)] (ex-cept ADE in aqueous LiCl) at higher compositioncan be attributed to the solvent structuredness.~ Sj is zero as aqueous salt solutions are structure?~eakers: But ~ S~ in the case of LiCl may be pos-inve due to disruption of the ordering of watermolecules in the primary solvation sphere aroundthe small-sized Li + .~ S~ is negative due to twopossible reasons: (1) the hydration of the first kindor hydrophilic hydration 17. of the nucleic acid

1moI"IoMct~

--::::::8:::::':=:=:::Jit:: LICINaCI

~_-rl KCI

(~eYT

0

..•

.z...•....out~~O

20 ADE LiCl 101)

Vn --o------~KCI

1'"D--6----6----_--..~ HaCI

I1lol'Y.llectrolytl\g;;;;~11 2 3 4

inaI"IolllctrolyW

Fig.2-(c,d) Variation of TAS? and TAS~inl (inset) of (c) CYTand (d) ADE with mol % electrolyte at 2SoC

GANGULY et al.:TRANSFER ENERGETICS OF NUCLEIC ACID BASES IN AQ. SALT SOLUTIONS 865

bases through the sites with formal positive andnegative sites, if any, and hydration of the secondkind i.e. formation of a hydrogen sphere throughthe hydrophobic sites around the incoming so-lutes'?" and (2) due to interaction of the cations(Li ", Na ", K+) and anion (cr ) with the formalnegative and positive charge centres of the solutes.The relative-order of a magnitude of TfiS?int willbe similar to that as described in the case of freeenergies of transfer for the solutes from water tothe mixed solvents under study. However, forADE in aqueous LiCl, Tfi S~ int is positive.(fiSI! + fi S~) is a small positive quantity and fi S~is also positive, while fi S~ for ADE is small andnegative as Li + is less polarizable and more sol-vated and therefore less likely to interact with theformal negative charge centres of the purine baseadenine.

Since the stability of intramolecular Hvbonds'?between DNNRNA base pairs viz. G-C andA- T IU, is the key to the stability of the doublestranded helices of DNA-RNA molecules, the ob-served trends of destabilization of these base unitsin these ionic cosolvent systems indirectly helpconclude that the said intramolecular'? H-bondswill be re-inforced as compared to that in water.Similar studies with other higher valent electro-lytes and. especially with respect to that in bio-fluids, might lead to give a thermochemical cluefor a possible antidote for the replication. of can-cerous cells.

AcknowledgementThanks are due to the UGC, New Delhi, for

financial assistance.References

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