Apparent Molal Heat Capacities of Organic Compounds in Aqueous Solution

Part 3.--o-Amino acids and related compounds

BY SERGIO CABANI,* GIOVANNI CONTI, ENRICO MATTEOLI

Istituto di Chimica Fisica, Universith di Pisa and

Laboratorio di Chimica Quantistica ed Energetica Molecolare del CNR, Pisa, Italy

AND ALESSANDRO TANI

Received 2 1 st April, 1976

Values of apparent molal heat capacities @Q, in the range 23"-55"C, were determined by adiabatic calorimetry for the following amino acids : glycine, a-alanine, or-aminoisobutanoic acid, valine, serine, threonine, sarcosine, dimethylglycine, betaine, 8-alanine, 8- and y-aminobutanoic acids, 6-aminopentanoic acid and c-aminohexanoic acid. Some hydroxy acids, sodium and ammonium salts of carboxylic acids, methyl and ethyl esters of acetic acid and glycine methylester hydrochloride have also been studied.

An attempt has been made to quantify the contribution to @cp associated with charge separation in amphionic molecules by comparing the experimental value (@s) for amino acids with those for similar uncharged molecules (@*::). thus obtained for +H3N(CH2), COO- compounds (rn = 2,3,4,5) are used in order to obtain some information about the interactions between neutral or charged amino and carboxylic groups. Effects connected with the methyl additions to N+ centres in glycine or ammonium salts are considered.

The A@* values (Bexp CP

Apparent molal heat capacities (O,,) of a-amino acids and related compounds in aqueous solutions were determined by Zittle and Schmidt,l Gucker et L I Z . , ~ ~ Kresheck and Benjamin and, more recently, by Spink and W a d ~ o . ~ As a part of a systematic study on a>,,. values of organic solutes in water,6* we have determined Ocp values for amino acids (glycine, a- and fi-alanine, L-valine and L-serine) already considered by others, extending the investigation within the temperature range 23"-55"C. In addition, QCp results of some related compounds, such as N-methyl derivatives of glycine, w-amino acids up to 6 carbon atoms, some hydroxy acids, ammonium or sodium salts of acetic, propionic and pentanoic acids, L-threonine, glycine methyl ester hydrochloride, as well as methyl and ethyl esters of acetic acid are reported.

These data and others related to dipeptides and diketopiperazines (some have already been published) 8 y are used to find out niore about (i) the effect due to charged groups attached to adjoining carbon atoms, and how this effect changes as the groups are increasingly separated by interposition of inethylene or peptide groups; (ii) the effect of alkyl substitution on the amino group of amphionic mole- cules; (iii) the effect of removal of the charged centres following the formation of cyclic molecules containing one or two peptide linkages.

EXPERIMENTAL A P P A R A T U S

The measurements of heat capacities of solutions were obtained employing an adiabatic calorimeter described previously.6 The vessel used contained about 170 cm3 of solution.

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S . C A B A N I , G . CONTI, E . MATTEOLI A N D A . TAN1 47 7

For each compound examined, three or more runs at concentrations ranging from 0.2 to 2 mol kg-' (m) were made in the temperature interval 23"-55°C.

The a)cP values at the temperature t are defined by

Qcp = (c-gwC")lnz where C is the heat capacity of the solution containing gw grams of water, c, is the heat capacity of a gram of water at the temperature T and n2 is the number of moles of solute. An exhaustive description of the method of determining C by adiabatic calorimetry has already been reported. The uncertainties in @cP values were estimated to be 6@,cP N 2 S / m J K-i mol-'.

M A T E R I A L S

Glycine, DL-a-alanine, p-alanine, L-valine, L-serine, L-threonine, glycine methyl ester hydrochloride, sarcosine, N,N-dimethylglycine, betaine, 6-aminopentanoic acid, &-amino- hexanoic acid, DL-P-aminobutanoic acid, a-aminoisobutanoic acid, glycolic acid, a-hydroxy- isobutanoic acid, sodium pentanoate and y-aminobutanoic acid were from Fluka AG, all puriss grade, except the two last compounds which were purum grade. Before use, hydroxy acids were dried in an oven at 130°C for one day; 8-aminopentanoic acid, N,N-dimethyl- glycine, DL-P-aminobutanoic acid and a-aminoisobutanoic acid were dried by storing in V ~ C U O over P20s for several days; they were then used without further purification. The remaining compounds were recrystallized from water or water + ethanol and dried as above. In all cases the melting or decomposition points agreed with the literature.

Methyl and ethyl acetate were from Carlo Erba RP grade. They were refluxed for 6 h with acetic anhydride and then distilled. The distillate was shaken with anhydrous potassium carbonate and then fractionally distilled under nitrogen. The purity was checked by g.1.c.

Ammonium acetate and propionate were obtained by mixing stoichionietric amounts of carefully titrated acid and ammonia.

All the solutions were prepared by weighing.

RESULTS

Data obtained in this work and, for the sake of comparison, by other authors, are reported in table 1. In the case of acetate, propionate and pentanoate salts,

For all other compounds, the number of data and their accuracy did not warrant an extrapolation of (Dcp values to zero solute concentration, hence only the arithmetic averages are reported. The errors are given as maximum deviations from the average.

and of Spink and W a d ~ o , ~ which, however, refer to zero solute concentration. For L-valine the QDCp value obtained is lower than that of Spink and Wadso, whereas that for glycine is greater than that of other However, from Spink and Wadso's data, a negative &D,,/dm for valine, and a positive one for glycine results.* So, the agree- ment between our data and those of Gucker and Spink and Wadso s is better than it appears from table 1 .

The difference between our value of QCp for ethyl acetate and that obtained by Stern lo from calorimetric enthalpies of solution (AH,) combined with its Cr, (1) value, is due to an error in the AHs values at 15°C. Stern carried out measurements

data were extrapolated against m+ to m3 = 0.

Our data for glycine and L-valine differ from those of Gucker

* Data obtained by Spink and Wadso were converted to @cP values by the relation @cp = (m 1000 +M2)cp- Y C W 1000

where cp is the heat capacity of a gram of a solution of molality my and M2 is the solute molecular weight. cw is the heat capacity of a gram of water. These @cp data, plotted against molality, show the concentration dependence mentioned in the text.

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418 A P P A R E N T MOLAL HEAT CAPACITIES

(their number is in parentheses) of AH, at 15 (3), 25 (23), 40 (9) and 50°C (6). The average values he obtained, except for T = 15"C, fit well a straight line of slope 191.6 J K-l mol-l, corresponding to a Qcp of 368.2 9 K-l rnol-l, which is in good agreement with the average value we have obtained in the range 23"-55"C.

Finally, our result for Qc0 of ammonium acetate is intermediate between the value reported by Leduc and Desnoyers l 1 and that calculated from NH,Cl, NaCl and

TABLE 1 .-APPARENT MOLAL HEAT CAPACITIES, @cp = f( T) , OF SOME AMINO ACIDS AND RELATED

COMPOUNDS IN THE TEMPERATURE RANGE 23-55"C, @Cp = C@;'+~(T-- 32")

aJg aJ;: no. of compound conc. range /J K-1 mol-1 b /J K-1 mol-1 experiments ref.

glycine 0.5-2 61.1k8.4 0.63f0.4 65.324.2 0 43.9 (46.9)a - -

0 146.0(141.0)a - -

0 36.8 1.4 46.4 DL-3-alanine 0.4-1.3 147.7k2.1 0.84k0.4 153.6k2.1

0 141.0 0.84 146.8

0 307.1 -- -

0 125.1 - -

L-valine 0.4 284.548.4 -0 287.4-t 8.4

L-serine 0.4-0.9 115.1+8.4 -0 117.2-t 8.4

L-threonine 0.4-0.8 208.448.4 -0 210.0f 12.6

N,N-dimethylglycine 0.3-0.9 182.848.4 2.7 40.4 201.728.4 sarcosine 0.5-1.1 105.0+6.3 0.96k0.4 112.1k6.3

betaine 0.4-0.7 151.9216.8 2.8 40.4 171.1f12.6 p-alanine 0.4-1 81.2k8.4 1.5 k0.4 91.228.4

0 76.6 1.4 86.2 P-aminobutanoic acid 0.4-0.8 164.4k4.2 -0 162.32 8.4 y-aminobutanoic acid 0.4-1 134.3 k 8.4 - 0 137.7+ 8.4 8-aminopentanoic acid 0.3-0.5 200.8f 8.4 -0 200.82 8.4 E-aminohexanoic acid 0.3-0.8 266.5 f4.2 N 0 266.95 4.2 a-aminoisobutanoic 0.4-0.8 225.52 4.2 -0.63f0.4 220.9f4.2

glycolic acid 0.4-1.3 142.354.2 -0 145.6k4.2 or-hydroxyisobutanoic 0.3-0.9 338.9k4.2 -0.84k0.6 333.0k4.2

acid

acid methyl acetate 0.5-0.9 282.8f8.4 0.84k0.4 288.3k8.4 ethyl acetate 0.7-0.8 374.9k8.4 -0.84f0.6 367.8k8.4

485.3 - - glycine methyl ester 0.4-0.8 142.7f 8.4 2.1 kO.8 156.9f8.4

ammonium acetate 0.4-2.1 85.4b - 1.8 72.@ 73.6c - -

103.3d - - 105.4 - -

ammonium propionate 0.4-2.2 177.e - 1.5 166.1b 191.6= - -

sodium pentanoate 0.4-0.9 3 10.4H 0.71 315Sb

hydrochloride

5 - - 4 - - 6

6

5 3 3 3 4

4 5 4 4 4

3 5

3 3

3

3

-

-

-

-

- - - 3

3 -

this work 5 2

this work 5 3

this work 5

this work 5

this work this work this work this work this work

3 this work this work this work this work this work

this work this work

this work this work

10 this work

this work 12 11 11

this work 11

this work

a With regard to data of ref. (3, values of @cp, obtained by measurements of heat of solution as a function of temperature, are reported in parentheses. The others were measured directly by a drop heat-capacity calorimeter. f~ Obtained by extrapolating the function Qp = f (m3) to zero concentram tion (m = molality). C Calculated by adding 33.5 J K rnol-' to the data of sodium acetate and propionate, respectively, reported by Parker.12 d Obtained by adding 33.5 J K-l mol-l (see above) to BEp of sodium acetate.

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TABL

E 2.-vAL

UES

OF

THE PARAMETERS O

F TH

E FU

NC

TIO

N :

(Dcp

= @

~p

(X)f

~C

@C

,(C

H~

)~

(J K

-’ m

0I-l)

; T

= 2

5°C

co

mpo

unds

X

0c

P(X

) @

cp(C

Hz)

n

r (c

oeff

. of c

orre

l.)

compounds

exam

ined

re

f.

DL-

a-al

anin

e ; DL

-OI-

3,5,

this

a-

amin

o ac

ids

-02C

CH

NH

t 64

.0

79.9

7 0.

9991

am

inob

utan

oic

acid

;

wor

k I

L-va

line ; L

-leuc

ine

m =

2,3

,4

n-C

rn&

rn+l

C02

H

-CH

2C02

H

161.

9 89

.1

3 0.

9988

-C

02H

75

.7

88.3

4

0.99

94

m =

1,2

, 3,4

16

-CH

ZCH

2NH

2 23

6.4

92.0

4

0.99

97

m =

3,4

, 5,6

-NH

Z 52

.3

92.0

4

0.99

97

m =

3,4

, 5, 6

n-

CmH

zrn+

1NH

2 -C

HZN

H2

144.

3 92

.0

4 0.

9997

m

= 3

,4,5

,6

16

n-C

mH

2,+1

CO

~NH

~ -C

HzC

O,N

HZ

92.5

88

.3

4 0.

9975

m =

2,4

, 7

11,1

2, th

is

-CO

,”HZ

3.8

88.3

8

0.99

59

m =

1,2

,4,7

w

ork

m =

3,4

,5,6

,7,8

m =

2, 3

,4, 5

,6,7

,8

-CH

2CH

2NH

:Br-

101.

7 86

.6

6 0.

9998

-NH

; Br

- -7

2.0

86.6

7

0.99

99

n-C

rnH

?,+1N

H:B

r- -C

H2N

H3+

Br-

15.1

86

.6 7

0.99

99

m =

2,3

.4,

5,6,

7, 8

17

a m

e is

the

num

ber o

f ca

rbon

ato

ms n

ot in

clud

ed in

X ; b

Num

ber o

f ex

perim

enta

l dat

a us

ed f

or th

e ca

lcul

atio

n of

the

reg

ress

ion

line ;

C W

hen

data

for

sod

ium

wer

e av

aila

ble,

a 33

.5 J

K-’

mol

-’ v

alue

was

add

ed to

thes

e.

0

Z

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480 A P P A R E N T MOLAL HEAT CAPACITIES

sodium acetate data from Parker's compilation.12 An analogous calculation for ammonium propionate provides a @,, value in fair agreement with our experimental result.

In the temperature range explored, the Qcp value for amino acids with small alkyl chains increases with temperature like the a,, of l 2 The derivative (aQ,,/aT), however, vanishes or changes sign as the size of the hydrocarbon portion of the molecule increases. The latter trend is common in tetra-alkylammonium salts l 3 and organic nionofunctional solutes which have a (d@,, /W) < 0.

An analogous situation arises with regard to the dependence of QCp on concentra- tion. Amino acids of lower molecular weight show a positive (a@,,/am) at low concentration, as do e1ectrolytes.l However, when the hydrocarbon region becomes dominating, (a@,,/am) is zero or negative.

Moreover, at,, values of amino acids, as already ~bserved ,~ fit quite well to a linear equation or" the type :

where @,,(X) and @,,(CH,) are the contribution to QCp of the functional group X and the methylene group respectively, and m, is the number of carbon atonis in the hydrocarbon portion of the molecule. This behaviour, already found for several series of monofunctional compounds,6 and the above mentioned dependence of @,, on temperature and concentration, suggest that a-amino acids behave as mono- functional compounds in which a region showing hydrophobic interactions with solvent can be distinguished from another where there are different kinds of interac- t i o n ~ . ' ~ * l5

Values of Qc,(X) and @,,(CH2) in eqn (1) for some typical classes of organic compounds are reported in table 2. The X group is defined so as to consider only the functional group, or the functional group plus one or two aliphatic carbon atoms. If one assigns the value m, = 1 to a suitable compound of each class, then the QcP(X) value, defined according to eqn (l), includes the intrinsic contribution of the group, a contribution due to the interactions with surrounding %ater, the difference between a CH3 and a CH2 group and other contributions such as those due to the motion of the centre of mass and to rotational-like motions.

Considering all the data of table 2, it is evident that the low QCp values of amino acids, compared with those of cornpounds with analogous molecular size, are mainly due to the amphionic character of these compounds, which causes the QCp (-OOCCHNH;) to be very low. Also the alkyl chain contribution to a,-,,

Q'cp = %,(W + mc@cp(CH2) (1)

which is less than it is in monofunctional solutes, is in part responsible for the low apparent molal heat capacity of a-amino acids. This latter effect is partly due to the charged centres, which probably reduce the hydrophobic character of the alkyl chain (compare for example @,,(CH2) of the n-alkylamine hydrobromides * with that of n-alkylamines) and partly to the data used for evaluating Qcp(CH2) of amino acids. In fact, two of the four R groups considered here have a branched chain which makes the @cp(CH2) value decrease, as may be seen by comparing e.g. @,,(CH2) calculated considering only n-carboxylic acids (88.7 J K-l mol-l) with that obtained including also branched chain carboxylic acids (87.0 J K-l mol-l).

* The independence of the value of iDcp(CH2) (86.6 J K-l mol-') from the definition of the groud X, ix., whatever carbon atom is given the value rnc = 1, is surprising. It could be accounted for, however, if the charges are strongly localized, and then the alkyl chain of monofunctional compounds should feel no charge effect. Note, however, that a k4.2 J K-' mol-' uncertainty in a iDcp value requires very accurate measurements ; such an error affects the slope by > k 2.1 J K-' mol-' when mc ranges from 1 to 4.

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S . C A B A N I , G . C O N T I , E . MATTEOLI A N D A . T A N 1 48 1

DISCUSSION

EFFECT OF TWO C H A R G E D CENTRES ON @cp O F O R G A N I C SOLUTES

To have a clearer insight into the effects which are responsible for the low OCp value of amino acids, the knowledge of the difference A@* (zwitterionic effect) between the actual QCp value and that of the corresponding neutral molecule would be very useful. Unfortunately, it is impossible to obtain the act, value of an amino acid in its uncharged neutral form, so we proceed in the following ways :

(a) By comparing the experimental value (QT) of an amino acid with that of a neutral isomeric molecule (e.g. glycine-glycolamide ;2 a-alanine-la~tarnide.~)

(b) By comparing @Fp" of an amino acid with that of the same uncharged molecule estimated :

(i) from the eqn (2) (D,,(H,NR'COOH) = @cp(RCO0H)+@cp(NH3)-@,,(H,), ( 2 )

where, at 25'C, QCp(NH3) = 75.3 J K--l mo1-1,6 QCp(H2) = 133.9 J K-l mol-' ; I 8

@>,,(RCOOH) from Konicek and Wadso.I6 (i i) for cr>-amino acids, from the arithmetic mean of iDcp for a, w-diamines and

u, w-dicarboxylic acids. (iii) as a sum of the group contributions to (Dcp for CH2, NH2, COOH, assuming

(c) By comparing differences between the Ocp of 3-amino acids and a-hydroxy acids with those between amines and corresponding alcohols (or between esters of amino acids and esters of hydroxy acids).

@c,(CH+CH3) = 2x@cp(CH2).

TABLE VALUES OF ACp FOR PROTON TRANSFER PROCESSES BETWEEN CARBOXYLIC ACIDS AND AMINES AT 25°C a

ACP carboxylic acid amine salt b /J K-1 mol-1

CH,COyNH,+

C H 3 C O ~ CH,NHi

CH3CO;nBuNHz CH3CH2CO;nBuNH: CH3(CH2)3CO;nBuNHl

CH3CH2COyNH; CH3(CHz)3CO,NH,f

CH3CH2COTCH3NHi CH3 (CH 2) 3 COT CHSNH 3'

- 154.8 - 151.5 - 162.8 - 166.1 - 162.8 - 174.1 - 167.4 - 164.0 - 175.3

a @cP data for carboxylic acids, propylamine and butylamine from ref. (16) ; for ammonia and methylamine from ref. (6). b For ammonium acetate, propionate and pentanoate (Dcp values see table 1 ; (Dcp value of ammonium pentanoate was calculated by adding 33.5 J K-l mol-' to the @cp of the corresponding sodium salt. (Dcp values for all other salts were calculated considering the following reaction

@cD's for n-alkyl amine * HBr and NHiBr- from ref. (11) and (17). RCOO-NH:+ RNHiBr- = RCOO-NH3R++ NHZBr-.

Furthermore, the comparison of the ADcp values for ring formation from linear uncharged compounds with the analogous Amcp values for cyclization of m-amino acids or dipeptides to give cyclic amides has been already discussed.8

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482 A P P A R E N T MOLAL HEAT CAPACITIES

On the other hand, the AC, value corresponding to the process of zwitterion formation in cu-amino acids :

is to be expected, as the separation between charged groups increases, to approach the value of AC, for the proton transfer reaction from carboxylic acids to amines.lg Some data for the latter process are summarized in table 3. No obvious effects of charged groups on alkyl chains emerge from these data ; an average AC, r - 167.4 & 8.4 J K-l mol-l for the proton transfer from a carboxylic to an amine group can therefore be assumed.

Among the various methods of calculating the zwitterionic efl-ect listed above, that in (b, iii) must be rejected. It leads to values of A@* < - 167.4 J K-' mol-1 for a-amino acids and much more negative for co-amino acids. However, we think that this value should be reached asymptotically by increasing separation between NH; and COO- groups. Certainly this discrepancy reflects an overestimation of NH, and COQH group contributions to the apparent molal heat capacity.? These latter, as already mentioned, include a part corresponding to the difference between group contributions of CM3 and CH2, a part due to the motion of centre of mass of the molecule, etc.

In table 4 are compared the 60" values obtained for different kinds of amino acids according to the procedures outlined above, except method (b, iii). The agreement among the data in different columns may be considered on the whole satisfactory. However, big differences are found, in the case of glycine and a-alanine, between values calculated following method (a) and those from method (b, i), first and second column respectively. On the basis of group contributions, the -CONM2 and -OH functions are almost equivalent to -NH2 and -COOH groups; in fact, for QcP(-OH + -CONH2) and QCp(-NH2 + --COQH), values of 138.1 and 125.6 J K-' mol-1 are obtained, respectively. Thus, the differences among the results in the first and second column of table 4 can be explained by supposing that some interaction between -OH and -CONH, groups in glycolamide and iactamide causes the apparent molal heat capacity of these molecules to differ from those for the case when the functional groups are assumed to be completely independent. The difference also found between values of zwitterionic effect A@* for p-alanine calculated following method (b, i) (second column of table 4) and from the arithmetic mean of BCp values of ethylenediamine and ethanedicarboxylic acid (third column of table 4), can be explained again on the basis of possible interactions between hydrophilic centres of these bifunctional solutes. Moreover, in the case of ethane- dicarboxylic acid, it was observed that the experimental QCp value is abnormally higher than those found for its higher homologues.21

Consider also the case of a-aminoisobutanoic acid for which a zwitterionic effect of -49.8 J K-l mol-l is calculated when method (b, i) is used. Instead, a value of -25.5 J K-l mol-1 is obtained by adding to the difference between the QCp values of a-aminoisobutanoic and a-hydroxy isobutanoic acids a value of 87.9 J K-l mol-1 corresponding to the difference between the 4jcp values of t-butyl- alcohol 2 2 and t-butylamine l6 (method c). This difference, on the other hand,

a constant @cp contribution of 65 J K-l mol-1 must be assigned to a hydrogen atom, irrespective of the nature of the atom attached to it (C, N or 0). Therefore, assuming that the values obtained by applying eqn (1) to homologous series of monofunctional compounds are the contributions of the hydrophilic groups, it is necessary to subtract 129.8 J K-' mol-1 from the @cp value of a bifunctional compound if it is calculated following the (b, iii) method. Note that 129.8 J K-1 mol-1 is almost the same value as the @cp of the H2 molecule in water at 25°C."

H,NRCOOH -+ +H3NRCOO- (3)

t As Nichols, Spink and Wadso have already pointed

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S . C A B A N I , G . C O N T I , E . MATTEOLI A N D A . T A N 1 483

greatly differs from the value of 25+8 J K-l mol-1 calculated as the average of the differences between the CDCp of primary or secondary alcohols and the (Dcp of primary amines having the same hydrocarbon skeleton. Clearly, the t-butyl group modifies the contributions of these groups with respect to those calculated from compounds with functional centres bonded to primary or secondary carbon atoms.

'rABLE 4.-DIFFERENCES A@*(J K-l m0l-l) BE1 WEEN @T OF AhtINO ACIDS AND @Fi OF SOME REFERENCE MOLECULES Ar 25"C, ESTIMATED ACCORDMG TO DIFFERENT PROCEDURES a

compound AQ*/J K-1 mol-1

glycine DL-a-alanine DL-a-aminobutanoic acid a-aminoisobutanoic acid L-valine

sarcosine N,N-dimet hylglycine

fi-alaniiie y-aminobutanoic acid 6-aminopentanoic acid E-aminohexanoic acid

DL-P-arninobutanoic acid

- 1 00.4b - 59.4' - 104.6b - 53.6'

- 56.1' - -- 49.w - - 66.1'

I

- - 80.8d - -111.7d

- - 108.8+4.2e I - 142.3_+4.2e - - l63.2+ 8.4e - - 184.1 k 4 . P

I - 113.8'

- -71.1g I

- - -

- -

- 136.4-f - 132.2f - 149.0-f - 165.7-f

-

a A@* = (@Gp-@Fi), @z values for amino acids are reported in table 1, except for a-amino- butanoic acid ; 5 @?: values were selected as explained below. b By comparison of isomers glycine- glycolamide and a-alanine-la~tamide,~ respectively. C = [@,cp(RCOOH) + Qp(NH3) - @cp(Hz)] ; @cp(NH3) = 75.3 J K-I mo1-l ;6 @cp(H2) = 133.9 J K-I mol-' ;I7 @cp(RCOOH) values from ref. (15). In the case of valine, the parent acid was n-pentanoic acid. d CaIculated as in (c) using for @cp(CH3NHZ) and @>cp[(CH&NH] data from ref. (6). e Calculated as in (c) but as an average of the results of all possible combinations of @,cp(RCOOH) I5 (except formic acid) and @,cp of amines.6s l6 The uncertainties are given as maximum deviations from the average. .f@&?,; = *(@cp[H 2N(CH2)mNH2] + (Dc~[HOOC(CH~),COOH]) using data for c(, w-diamines and a,o-dicarboxyhc acids from ref. (21). The @cp of HOOC(CHz)5COOH was estimated by adding 87.9 J K-l mol-1 to @cp of HOOC(CH2)4COOH. 9 By comparison of glycine and glycolic acid (see table 1). For the process ROH -+ RNH2 a AQc, of -25.1 J K-l mol-l was estimated by examining data for amines I6 and aliphatic alcohols.22 h By comparison of cc-aminoisobutanoic acid and a-hydroxyisobutanoic acid. A value of - 86.6 J K-I mol-1 for A@cp of the process : t-BuOH 22

-+ t-BuNH 2 1 was estimated.

The average value of A@* for the first five a-amino acids of table 4 is - 59 & 8 J K-l rnol-l, taking into consideration only method (b, i). No effects due to the kind of alkyl group bonded to the a-carbon atom are present, within the limits of our experi- mental accuracy. Also the introduction of an -OH group into the alkyl radical does not modify the A W values; compare for example the pair a-alanine --+ serine (AQCp = -25 J K-l mol-l) with acetic acid l6 -+ glycolic acid (A@cp = -21 J K-l mol-l)), or the pair a-aminobutanoic acid -+ threonine (ACDcp = - 12.6 J K-l mol-l) with isobutanoic acid l6 --+ a-hydroxyisobutanoic acid (A@'cp = 4.2 J K-l mol-l).

A strong decrease in A@* is observed, when the charged centres are separated (see the series of aminobutanoic acids and w-amino acids), or when alkyl groups are bonded to nitrogen (sarcosine and dimethylglycine). As the charged groups are increasingly separated, the absolute value of A@* increases and approaches the AC,

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484 A P P A R E N T M O L A L H E A T C A P A C I T I E S

value for the proton transfer process from a carboxylic acid to a primary amine. This trend could suggest that the NHZ and COO- groups no longer interact when they are five, or more, bond lengths apart. This interpretation, however, disagrees with the value of the methyleiie contribution to <Dcp in the co-amino acid series. In fact we have obtained, for the series fi- alanine + c-amino hexanoic acid, a <Dcp(CH2) value of 62 J K-l mol-l, which is much less than the one found for ionic and non-ionic organic monofunctional solutes (88 J K-1 mol-l, see table 2). QCp measurements on co-amino acids with charged groups more than six methylene units apart will be useful to establish the maximum interaction distance of NHS and COO- centres. Short of this information, however, we can still say that when these groups are in the same molecule they affect the hydrocarbon chain up to a greater distance than one would conclude on the basis of QCp values for carboxylic acids salts and for n-alkyl- ammonium cations.

(Dcp V A L U E S OF CATIONIC [NH; (CH2),,COOH] A N D A N I O N I C [NH2(CH,),COO-) FORMS OF a-AMINO ACIDS

The interaction range of a charged group with the chain seems to be enlarged not only by a second charged group, but also by a hydrophilic uncharged group, as in the cationic [NH; (CH,),COOH] and anionic [NH2(CH2),,C00-] forms of a-amino

TABLE 5,--<DcP VALUES (J K-l mol-l) IN WATER AI- 25°C OF CI-H3N+(CH2),COQH,

AND [-COO- * NH:] H2N(CH,)mCOO-NH: AND OF CONTRIBUTIONS OF THE GROUPS [Cl- * HJN']

compound @CDU @cp(CI-* NH:)b @cp(-COO-. . . NH;)'

- CI-H3N+CHZC02CH3 142.7 - 75.3

CI-H~N+(CHZ)~CO~H 82.8 - 105.4 - Cl-H3N'(CH2)3C02H 102.5 - 169.5 - Cl-H3N+(CH2)4C02 H 190.0 - 176.6 -

M2N(CH2)2C0~NH4+ 119.2 - H2N(CH2)3COFNH: 193.3 - H2N(CH2)5COy NH: 375.7 - - 74.5

- CI-HSN'CH2C02H 43.5 - 56.5

H2NCHzCOYNH: 96.7 - 6.7 - 52.3 - 68.6

(1 These @cp values were obtained : (i) Qcp(Cl-NH+3CH2COOCH3) from direct calorimetric

(iii) @cp(HzN measurements ; (ii) @cp(Cl-NH+3(CHz)mCOOH) = @cp(HC1) +(DC~(H~N+(CH~)~COO-) -lCp, The ACp,l values were taken from ref. (24) ; (Dcp(HCI) = - 136.4 J K-' mol-1.'2 (CH2)mCOO-NH:) = (I,cp(H3N+(CH2)mCOO-) + @cp(NH,Cl) - Qcp(HC1) + A Cp,2. values were taken from ref. (23); @cp(NH4CI) = -56.5 J K-' mol-1.12

b The (Dcp(-NH;Cl-) value was evaluated according to the following relation : @cp(---NHSCI-) = Qc,(Cl-H3N+(CH2),COOH) - (D,c~(H(CH~),COOH)+ 65 J K-I mol-'. The @cP values of H(CH2)mCOOH were taken from ref. (16) ; 65 J K-l inoI-' is the value of @cp assigned to a hydrogen atom.20 For glycine methyl ester hydrochloride, 65 J K-I mol-I were added to the difference between @cp(C1-H3N+-CH2-COOCH3) and <DcP(H-CH2-COOCH3).

C The @c,(-COO NH:) value was evaluated according to the relation : Qcp(-COO-NH:) = @~~(H~N(CH,),CO~-NH:)-(DC~(H~N(CH~)~H) + 65 J K-' mol-l. The (DcP values of H2N fCH2)mH were taken from ref. (16), except that of methyl amine [ref. (6)] and that of ethyl amine, evaluated from the equation reported in table 2.

The AC'p,z

acids. This is suggested if one examines the QCp values of the salts of these ionic species obtained from the AC, values of the reactions (ACp,l and ACp,2 respectively) :

Cl-NH; (CH2),COOH --+ NH; (CH2),,COO- + HCl (4) ( 5 ) NH$(CH2),,COO- + NH,Cl+ NH2(CH2),COO-NHz + HC1

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S. CABANI, G. CONTI, E. MATTEOLI A N D A. TAN1 485

quoted in the literature,23* 24 combined with Ocp(HC1),12 @,-,(NH4C1) 1 2 and OCp values of zwitterionic forms of w-amino acids (see table 1). Table 5 reports the values so obtained, together with the QCp value of glycine methyl ester hydrochloride and the values of Ocp contributions by the (NHZCI-) and (COO-NH:) groups." The trend of the latter values with increasing separation between functional groups shows that a hydrophilic uncharged group greatly affects the contribution of the charcged group up to three bond lengths. However, in monofunctional solutes (see table 2), the effect of the charged group is not felt beyond the SI carbon atom.

TABLE 6.-cOMPARISON OF A@cp FOR METHYL ADDITION TO CHARGED OR UNCHARGED CENTRES, rN J K-' mol-' A'r T = 25°C

I

-C-OH I

I -N- I -N+-

I

I

I 1 CHz-N+-

coo- f lCR3 Q)CP a A Q C P CDCp b I O c p mcp Amcp @CPO A%

110.5 108 .O 36.4 44.0

126.0 134.7 34.7 77.7

- - 41.9 - 30.9

1 253.1 154.8 12.6 61.1

2 363.6 262.8 49.0 105.1

3 389.6 397.5 83.7 182.8

4 - - 125.6 151.9

a Ref. (22). b Ref. (6). CH3NH2 9 HCI was taken from ref. (17), converting it from hydro- bromide to hydrochloride. ' The compounds considered here are, from the top : glycine, sarcosine, N,N-dimethylglycine and betaine. For the sake of convenience, in this table the -CH2-COO- group is to be considered as a methyl group.

I N T R O D U C T I O N O F M E T H Y L G R O U P S O N N I T R O G E N OF CI-AMINO A C I D S

In table 6 data for the introduction of a methyl group to the centres

-C-OH, I \N-, >"( and --OOCCH&+< / I are compared. the trend in AC, values for the reaction of proton addition to saturated amines is most probably to be ascribed to the fact that the QcP contribution of the charged nitrogen centre decreases as the number of hydrogens bonded to it decrease. Data reported in table 6 reinforce this idea, in fact,

one can note that the progressive addition of methyl groups to -C-OH and N-

involves an average increment of - 117.2 J K-l mol-l. On the other hand, in the

case of methyl addition to the \N+/ and --OOCCH2N+( centres, the average

increment of QC,, is 4 117.2 J K-l rnol-' going from primary to quaternary nitsogens. We observe, however, that while in the series of methylamine salts this increment is regular, it does not behave regularly for the changes glycine -+ sarcosine -+ dimethyl- glycine -+ betaine, for which 42, 79 and -29 J K-I rnol-' are found respectively.

* The values of @cp (NHiCI-) and @cp (COO-NH:) are not directly comparable with those reported in the third column of table 2, since these latter contain, owing to the method by which they have been calculated, the contribution to @cp of a hydrogen atom, and, iDcp(NHf,C1-), also the difference [@'cp(Cl-) - @cp(Br-)l.

As already observed,6,

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486 APPARENT M O L A L H E A T C A P A C I T I E S

This trend is not explained easily. It is possible, however, that sarcosine in solution is in a preferred conformation (gauche) which allows the two hydrogen atoms in \NHZ to establish hydrogen bonds with water. The dimethylglycine, on the

contrary, could be stabilized by a conformation which allows the -NH+ to come into

contact with -COO-. The methyl groups remain in this case exposed to water and, by recovering their hydrophobic character, cause the increase in the aCp value for dimethylglycine with respect to sarcosine.

I I

/

This work has been supported with financial assistance from C.N.R. (Roma). The contribution to the experimental work of Mr. M. Mengheri is gratefully acknowledged.

C. A. ZittIe and C. L. A. Schmidt, J. Biol. Chem., 1935, 108, 161. F. T. Gucker, W. L. Ford and C. E. Moser, J. Phys. Chem., 1939, 43, 153. F. T. Gucker and T. W. Allen, J. Amer. Chem. SOC., 1942, 64, 191. G. C . Kresheck and L. Benjamin, J. Phys. Chem., 1964,68, 2476. C. H. Spink and I. Wadso, J. Chem. Thermodyn., 1975,7, 561. S. Cabani, G. Conti, A. Martinelli and E. Matteoli, J.C.S. Faraday I , 1973, 69, 2112.

S. Gabani, G. Conti and E. Matteoli, Quatrisme Confe'rence Internationale de Thermodynamique Chimique (Montpellier, France, 1975), vol. 5, p. 27. S. Cabani, G. Conti, E. Matteoli and A. Tani, Chimica e Industria, 1976, 58, 215.

' S. Cabani, G . Conti and E. Matteoli, J. Solution Chem., 1976, 5, 125.

lo J. H. Stern and A. Hermann, J. Phys. Chem., 1968,72, 364. l 1 P. A. Lkduc and J. E. Desnoyers, Canad. J . Chem., 1973, 51,2993. l2 V. B. Parker, Thermal Properties of Aqueous Uni-univalent ElectroZytes (NSRDS-NBS 2, 1965). l3 M. J. Mastroianni and C. M. Criss, J . Chem. Thermodyn., 1972, 4, 321. l4 F. Franks and D. S . Reid, in Water a Comprehensive Treatise, ed. F . Franks (Plenum Press,

l 5 K. Kusano, J. Suurkuusk and I. Wadso, J. Chem. Thermodyn., 1973, 5,757. l6 J. Konicek and I. Wadso, Acta Chem. Scand., 1971, 25, 1541.

P. A. LCduc, J. L. Fortier and J. E. Desnoyers, J. Phys. Chem., 1974, 78, 1217. l8 D. A. Alexander, D. J. T. Hill and R. White, Austral. J . Chem., 1971, 24, 1143. l9 J. T. Edsall, J. Amer. Chem. SOC., 1935, 57, 1506. 2o N. Nichols, C. H. Spink and I. Wadso, Quatrisme Confe'rence Internationale de Thermo-

21 N. Nichols, R. Skold and I. Wadso, Quatri2me Confe'rence Internationale de Thermodynamique

22 D. A. Alexander and D. J. T. Hill, Austral. J. Chem., 1969, 22, 347. 23 J. W. Larson and L. G. Hepler, in Solute-Solvent Interactions, ed. J. F. Coetzee and C. D.

24 J. J. Christensen, J. L. Oscarson and R. M. Izatt, J. Amer. Chem. SOC., 1968, 90, 5949.

New York/London, 1973), vol. 2, p. 323.

dynamique Chimique (Montpellier, France, 1975), vol. 8, p. 49.

Chimique (Montpellier, France, 1975), vol. 7, p. 43.

Ritchie (Marcel Dekker, New York, 1969), p. 15.

(PAPER 6/765)

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