The paper describes synthesis method and colloid-chemical properties of novel α-amino acid based polyesters
with controllable hydrophilic-lipophillic balance. Glutamic acid and diols of different nature based
polyesters were obtained via low-temperature activated polyesterefication. Such polymers are able to form
micellar structures in self-stabilized water dispersion. Solubilization of water insoluble dyes Sudan and
toluene in polymer water solution was studied. Due to micelle forming ability and prognosticated biodegradability
to non-toxic products, obtained polymers are promising materials for formation of novel dispersed
drug delivery systems.
When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/3507

Dron, I.A.

Nosova, N.G.

Puzko, N.V.

Samaryk, V.Ja.

Tarnavchyk, I.T.

Varvarenko, S.M.

Voronov, A.S.

Voronov, S.A.

Electronic Sumy State University Institutional Repository

PROCEEDINGS OF THE INTERNATIONAL CONFERENCE NANOMATERIALS: APPLICATIONS AND PROPERTIES Vol. 1 No 1, 01NDLCN13(4pp) (2012)   2304-1862/2012/1(1)01NDLCN13(4) 01NDLCN13-1  2012 Sumy State University Colloidal and Chemical Properties of Polyesters Based on Glutamic  Acid and Diols of Different Nature  S.M. Varvarenko, N.V. Puzko, A.S. Voronov, I.A. Dron, I.T. Tarnavchyk,  N.G. Nosova*, V.Ja. Samaryk, S.A. Voronov   Lviv Polytechnic National University, 12, Bandera Str., 79013, Lviv, Ukraine  (Received 28 June 2012; published online 08 August 2012)  The paper describes synthesis method and colloid-chemical properties of novel α-amino acid based pol-yesters with controllable hydrophilic-lipophillic balance. Glutamic acid and diols of different nature based polyesters were obtained via low-temperature activated polyesterefication. Such polymers are able to form micellar structures in self-stabilized water dispersion. Solubilization of water insoluble dyes Sudan and toluene in polymer water solution was studied. Due to micelle forming ability and prognosticated biodeg-radability to non-toxic products, obtained polymers are promising materials for formation of novel dis-persed drug delivery systems.  Keywords: Pseudo-poly(amino acid), Biodegradability, N,N'-dicyclohexylcarbodiimide, Polymer micelle, Sol-ubilization, Surface tension, Drug delivery systems.   PACS numbers: 81.16.Dn, 82.35.Jk                                                             * nnosova@polynet.lviv.ua 1. INTRODUCTION   Biodegradable and biocompatible polymer materials with non-toxic degradation products are widely used for different biomedical applications. Hereby, develop-ment of new synthesis methods thereof becomes im-portant scientific task.  Nature acid based polyesters have been used as synthetic suture materials [1] and biodegradable drug delivery systems [2] long before. In this work novel method of α-amino acid and it derivatives based polyes-ters is described. Control of hydrophilic-lipophillic bal-ance (HLB) of polyesters via polypolyethylene and pol-yoxypropylene fragments introduction gives opportuni-ty to form polymers able to self-assembly in core-shell miccelar structure in water medium. Due to amino acid bonding in main polymer chain via ester bond, such compounds refer to the pseudo-poly(amino acid) class- amino acid based polymers with non-peptide bond in main polymer chain. Such struc-ture provides a set of advantages over nature occurring poly(amino acid)s, e.g. no immune response in recipient organism (due to the peptide bond absence), on the oth-er hand, compatibility to the poly(amino acid)s struc-ture provides biodegradability and low toxicity of poly-mers and degradation products thereof. Accordingly, such polymers are promising materials for formation of novel dispersed drug delivery systems.      2. SYNTHESIS OF POLYESTERS BASED ON GLUTAMIC ACID AND DIOLS OF DIFFER-ENT NATURE   Glutamic acid and diols of different nature based polyesters were obtained via low-temperature activated polyesterefication, according to the Fig. 1. As activator of esterefication reaction was used N,N'-dicyclohexylcarbodiimide known agent of carboxyl group activation. Reagent ratio in pseudo-poly(amino acid)s synthesis allows to control in this system poly-condensation degree and terminal functional groups.      N C N+NHCNNHC NOO OOA2DCC Active ester (AE)Glu(A)n AE + OH ORHkqm-n.DCCkO OOHOHAOO OOAQRQQ = O H OAH R = H, -CH3I II   Fig. 1 – Synthesis of glutamic acid and diols based polyesters using coupling agent DCC  As amino group is more nucleophilic center than hydroxyl group, it was necessary to provide amino group protection. We optimized conditions of amino group blocking and deblocking, one can observe in Ta-ble 1 protection groups and N-derivatives of glutamic acid which were used in this work.  Table 1 – Protective groups and N-derivates of glutamic acid  Tert-butoxycarbonyl protective group  (Boc) O OOHOHNHOO  Acetyl pro-tective group (Ac) OHONHO CH3OHO  Trifluoroacetyl protective group (TFA) O OOHOHNHOFFF N-stearoyl glutamic acid   Accept reaction of peptide bond formation, other side reactions influence on the reaction selectivity – cycle esters formation and rearrangement of active ester according to fig.2.   O OONC NO HANHC NOO OOArearrangement  Fig. 2 – Rearrangement of active ester of glutamic acid and DCC to passive amide  OH OHONHOO CH2 CH316 S.M. VARVARENKO, N.V. PUZKO, A.S. VORONOV , ET AL. PROC. NAP 1, 01NDLCN13 (2012)   01NDLCN13-2 The running of these reactions was confirmed by mass spectroscopy. These reactions have significant effect on the polycondensation degree, but optimal pro-cess conditions for maximal suppression of these reac-tions were ascertained. Furthermore, it is well known [4], it’s necessary to introduce nucleophilic additives in reaction mixture to achieve high conversion. On prac-tice 4-dimethylaminopyridine (DMAP) is widely used. It turned more efficient in comparison with 1,4-diazabicyclo[2.2.2]octane (DABCO) and triethylamine. Polycondensation was successfully conducted using N-stearoyl glutamic acid, glutamic acid with acetyl pro-tective group and diols in the range of molecular mass 100-2000 Da. Polycondensation degree made 75-85% of maximal calculated one. Using glutamic acid with tert-butoxycarbonyl protective group, we obtained polyesters with polycondensation degree 1-3. We didn’t succeed to obtain polyesters based on ethyleneglycol and propyl-eneglycol, the same as we didn’t obtain polymers with terminal carboxyl groups (fig. 1, Q=I).  The first can be explained by high probability of cyclization reaction for these alcohols. The second – by side reaction of rear-rangement of active ester, therefore the reaction should be conducted in the condition of alcohol excess.  Hereby, developed method was used for synthesis of polymers, containing hydrophilic (polyethyleneglycol) and lipophilic (polypropyleneglycol and N-stearoyl glu-tamic acid) fragments. Hydrophilic-lipophillic balance of such polymers can be controlled by different frag-ments ratio and polyethyleneglycol and polypropyl-eneglycol molecular mass. Polymer structure was con-firmed by NMR- and IR-spectroscopy, molecular mass was determinated by gel-penetrative chromatography.     3. SURFACE-ACTIVE AND COLLOIDAL PROP-ERTIES OF  GLUTAMIC ACID BASED POLY-ESTERS   Colloidal and chemical properties of obtained poly-esters strongly depend on their composition. Thus poly-esters co-Glu(HCl)-co-PEG or co-Glu(HCl)-co-PPG (the-se polyesters are formed after co-Glu(Boc)-co-PEG and co-Glu(Boc)-co-PPG deblocking, molecular mass of PEG and PPG – 100-600 Da) are water soluable. Water solu-tions of such polymers don’t posses colloid-chemical properties even at high polymer concentration.  Co-Glu(St)-co-PEG or co-Glu(St)-co-PPG type poly-mers with the same molecular mass of PEG and PPG are water insoluble, they are not able to form stable self-stabilized dispersions in water and haven’t ability to de-crease surface tension on water-air interface. Only co-Glu(Ac)-co-DEG (synthesized via polycondensation of Glu(Ac) and diethylenglycol (DEG))  among this type of polymers shows significant surface activity and self-stabilized water dispersions. This copolymer forms stable water dispersion with surface tension 47-49 mN/m. The last demonstrates that surface-active properties and properties of water dispersion self-stabilization can be achieved via hydrophilic/lipophilic fragments ratio in pol-ymer chain. In this work polyesters with necessary prop-erties were obtained due to forming of polymers with complex architecture. Thus Glu(St) based polyesters were obtained using mixture of  equal molar quantities of PEG and PPG of different molecular mass as diol (Fig. 3).    mnkOOO OOHNHOCH3CH3OOO ONHOCH3   Fig. 3 – Schematic structure of polyester synthesized via poly-condensation of Glu(St) and mixture of  equal molar quanti-ties of PEG and PPG   Two different diols and their part in macromolecule structure were confirmed by NMR-spectroscopy. Large majority of polyesters with different diols posses ability to form self-stabilized water dispersion. Such polyes-ters show higher surface activity than polyester mole-cules with one type of alcohol (fig. 4).  20,0030,0040,0050,0060,0070,0080,00Surface tension, mN/mPolyesters synthesized using one type of diolsPrecursor-based polyestersPolyesters synthesized using two type of diols  Fig. 4 – Surface-active properties of polyesters synthesized via different methods  Though, entering of diols of different structure in polymer macromolecule is not equivalent, it leads to irregular block structure and significant nonuniformity of functional distribution. In this case control of sur-face-active and colloidal properties of polyesters with different fragments is realized incompletely. In this case, should expect that regular sequence of blocks of different nature allows to achieve higher surface activi-ty. Polyester synthesis with regular block sequence conducted via prior precursor synthesis with the follow-ing structure:   n16 16OOOHO CH2 CH3ONHOOOHOR NHO CH2 CH3  Fig. 5 – Structure of precursor used for polyester synthesis with regular block sequence. In the case R=H – Glu(St)-PEG-Glu(St),  R=CH3 – Glu(St)-PPG-Glu(St)  Synthesized precursors according to their nature are dicarboxylic acids consisting of glutamic acid resi-due bonded by polyoxypropilene(polyoxyethylene)  COLLOIDAL AND CHEMICAL PROPERTIES OF POLYESTERS … PROC. NAP 1, 01NDLCN13 (2012)   01NDLCN13-3 chains with different molecular mass. Such precursors were used for polyester synthesis according to the scheme on Fig. 1 instead of glutamic acid or its deriva-tives. NMR-spectroscopic study confirmed precursors structure and showed that 83-87% of portal carboxyl groups are γ-carboxyl groups. It facilitates reaction in comparison with glutamic acid or its derivatives due to the carboxyl group reactivity equalization. For pseudo-poly(amino acid)s synthesis we used precursors with PPG in the range of molecular mass 130-1000 Da. Ob-tained polyesters have the same structure as polyesters synthesized using mixture of equal molar quantities of PEG and PPG, but differ by strict regular structure. This fact was confirmed by NMR-spectroscopy. As ex-pected, polyesters with regular molecules structure posses more strongly pronounced surface-active proper-ties (Fig. 4). More over conducted studies show that majority of precursor-based polymers hane complex type of surface tension isotherm with strongly pro-nounced two breaking points (Fig. 6).  20,0030,0040,0050,0060,0070,0080,000,00 0,10 0,20 0,30 0,40Surface tension, mN/mPolymer concentration, %4. (Glu-St—PPG1000—Glu-St)--PEG40020,0030,0040,0050,0060,0070,0080,000,00 0,05 0,10 0,15 0,20Surface tension, mN/mPolymer concentration, %3. (Glu-St—DPG—Glu-St)--PEG40020,0030,0040,0050,0060,0070,0080,000,00 0,10 0,20 0,30 0,40 0,50Surface tension, mN/mPolymer concentration, %2. (Glu-St—PPG400—Glu-St)--PEG40020,0030,0040,0050,0060,0070,0080,000,00 0,02 0,04 0,06 0,08 0,10 0,12 0,14Surface tension, mN/mPolymer concentration, %1. (Glu-St—PPG400—Glu-St)--PEG300  Fig. 6 – Surface tension curves of selected precursor-based polyesters  The first breaking point (starting from coordination zero) has to be considered as critical micelle concentra-tion (CMC) (CMC values of few polymer samples are given in Table 2).   Table 2 – Selected characteristics of precursor-based polyesters  № Polyester based on (Glu-St—DPG—Glu-St) precursor CMC1% CMC2 % Molecular mass(accor-ding to GPC) HLB 1 Glu-St—DPG—Glu-St-- PEG400 0,0042 0,0337 2980 9,4 2 Glu-St—DPG—Glu-St-- PEG600 0,0051 0,0532 3405 13,7  Precursor-based polyesters form self-stabilized pol-ymer dispersions with unimodal nanometer disperse phase distribution at negligibly higher concentration than CMC (Fig. 7.)  Polymer concentration increasing in water disper-sion leads to complex but organized dispersed phase rearrangement. This fact is displayed by the second breaking point on the surface tension isotherm curve. Furthermore, particle size distribution curve also has dependence on the polymer concentration (Fig. 7). Pre-sented data shows some average diameter increase of dispersed phase first mode with polymer concentration increase. Simultaneously, one can observe formation of the second mode particles (approaching the second breaking point concentration on the surface tension iso-therm curve) and the third mode particles formation at the concentration higher than the second breaking point concentration on the surface tension isotherm curve.    Fig. 7 – Characteristic distribution curve obtained using DLS method  The character of particle distribution changing indi-cates on the formation of disperse phase particle of com-plex structure with regions of different properties due to the hydrophilic and lipophilic fragments in polyester molecules. This conclusion is confirmed by solubilization curves of insoluble organic substances. Toluene and su-dan (III) solubilization curves is presented on Fig. 7.  Noticeable solubilization of sudan is observed under CMC. As about toluene solubilization – it can be ob-served at concentration higher than the second break-ing point concentration on the surface tension isotherm curve. Thus, regions able to solubilize toluene in dis-perse phase can be formed at concentration higher than the second breaking point concentration on the surface tension isotherm curve. One can observe disperse phase particle formation of the second and third mode on the size distribution curve.    S.M. VARVARENKO, N.V. PUZKO, A.S. VORONOV , ET AL. PROC. NAP 1, 01NDLCN13 (2012)   01NDLCN13-4 0,00E+001,00E-052,00E-053,00E-054,00E-055,00E-056,00E-057,00E-058,00E-059,00E-051,00E-040 0,02 0,04 0,06 0,08 0,1 0,12 0,14 0,16 0,18 0,2 0,22g dye /mlsolutionPolymer concentration, %Sudan (III) solubilization(GluSt-DPG-GluSt)--PEG-400(GluSt-DPG-GluSt)--PEG-600(GluSt-PPG-400-GluSt)--PEG- 300GluSt-PPG-1000-GluSt)-- PEG-400 -1,0E-049,0E-041,9E-032,9E-033,9E-034,9E-0300,050,10,150,20,250,30,350,40,450,50,550,60,650,70,750,80,850,90,95 11,05g toluene /ml solutionPolymer concentration, %Toluene solubilization(GluSt-DPG-GluSt)--PEG-400(GluSt-PPG-400-GluSt)--PEG-300(GluSt-DPG-GluSt)--PEG-400(GluSt-PPG-1000-GluSt)--PEG-400(GluSt-PPG-1000-GluSt)--PEG-400(GluSt-DPG-GluSt)--PEG-600  Fig. 8 – Curves of toluene and water insoluble dye Sudan (III) solubilization 4. CONCLUSIONS   Novel polyesters based on glutamic acid (or its de-rivatives) and diols of polyoxyethylene/ polyoxypropyl-ene type were synthesized. Developed technique allows to obtain polyester with different hydrophilic-lipophillic balance using the ratio of hydrophilic/lipophillic frag-ments in polyester molecules. The structure and com-position of synthesized polymers were confirmed using NMR, IR-spectroscopy, molecular mass was settled via gel-penentration chromatography. Such polyester pos-ses surface-active properties, and are able to form self-stabilized water dispersion. These dispersions solubil-ize water insoluble compounds. Thus obtained polyes-ters are promising materials for formation of dispersed drug delivery systems.        REFERENCES  1. I.A. Trail, E.S. Powell, J. Noble, J. Hand Surg.-Brit. Eur. 14, No4, 422 (1989). 2. D.L. Wise, H. Rosenkrantz, J.B. Gregory, H.J. Esber, J. Pharm. Pharmacol. 32, 399 (1980). 3. J. Kohn, R. Langer, Polym. Mater. Sci. Eng. 51, 119 (1984). 4. B. Neises, W. Steglich, Angew. Chem. Int. Ed. 17, 522 (1978). 

Colloidal and Chemical Properties of Polyesters Based on Glutamic Acid and Diols of Different Nature

SocioEconomic Challenges Journal (Sumy State University)

PROCEEDINGS OF THE INTERNATIONAL CONFERENCE NANOMATERIALS: APPLICATIONS AND PROPERTIES 
Vol. 1 No 1, 01NDLCN13(4pp) (2012) 
 
 
2304-1862/2012/1(1)01NDLCN13(4) 01NDLCN13-1  2012 Sumy State University 
Colloidal and Chemical Properties of Polyesters Based on Glutamic  
Acid and Diols of Different Nature 
 
S.M. Varvarenko, N.V. Puzko, A.S. Voronov, I.A. Dron, I.T. Tarnavchyk,  
N.G. Nosova*, V.Ja. Samaryk, S.A. Voronov 
 
 Lviv Polytechnic National University, 12, Bandera Str., 79013, Lviv, Ukraine 
 
(Received 28 June 2012; published online 08 August 2012) 
 
The paper describes synthesis method and colloid-chemical properties of novel α-amino acid based pol-
yesters with controllable hydrophilic-lipophillic balance. Glutamic acid and diols of different nature based 
polyesters were obtained via low-temperature activated polyesterefication. Such polymers are able to form 
micellar structures in self-stabilized water dispersion. Solubilization of water insoluble dyes Sudan and 
toluene in polymer water solution was studied. Due to micelle forming ability and prognosticated biodeg-
radability to non-toxic products, obtained polymers are promising materials for formation of novel dis-
persed drug delivery systems. 
 
Keywords: Pseudo-poly(amino acid), Biodegradability, N,N'-dicyclohexylcarbodiimide, Polymer micelle, Sol-
ubilization, Surface tension, Drug delivery systems. 
 
 PACS numbers: 81.16.Dn, 82.35.Jk 
 
 
                                                          
* nnosova@polynet.lviv.ua 
1. INTRODUCTION  
 
Biodegradable and biocompatible polymer materials 
with non-toxic degradation products are widely used 
for different biomedical applications. Hereby, develop-
ment of new synthesis methods thereof becomes im-
portant scientific task.  
Nature acid based polyesters have been used as 
synthetic suture materials [1] and biodegradable drug 
delivery systems [2] long before. In this work novel 
method of α-amino acid and it derivatives based polyes-
ters is described. Control of hydrophilic-lipophillic bal-
ance (HLB) of polyesters via polypolyethylene and pol-
yoxypropylene fragments introduction gives opportuni-
ty to form polymers able to self-assembly in core-shell 
miccelar structure in water medium. 
Due to amino acid bonding in main polymer chain 
via ester bond, such compounds refer to the pseudo-
poly(amino acid) class- amino acid based polymers with 
non-peptide bond in main polymer chain. Such struc-
ture provides a set of advantages over nature occurring 
poly(amino acid)s, e.g. no immune response in recipient 
organism (due to the peptide bond absence), on the oth-
er hand, compatibility to the poly(amino acid)s struc-
ture provides biodegradability and low toxicity of poly-
mers and degradation products thereof. Accordingly, 
such polymers are promising materials for formation of 
novel dispersed drug delivery systems.     
 
2. SYNTHESIS OF POLYESTERS BASED ON 
GLUTAMIC ACID AND DIOLS OF DIFFER-
ENT NATURE  
 
Glutamic acid and diols of different nature based 
polyesters were obtained via low-temperature activated 
polyesterefication, according to the Fig. 1. As activator 
of esterefication reaction was used N,N'-
dicyclohexylcarbodiimide known agent of carboxyl 
group activation. Reagent ratio in pseudo-poly(amino 
acid)s synthesis allows to control in this system poly-
condensation degree and terminal functional groups.    
 
 
N C N
+
NH
CN
NH
C NO
O O
O
A
2
DCC Active ester (AE)Glu(A)
n AE + OH O
R
H
k
q
m
-n.DCCk
O O
OHOH
A
O
O O
O
A
Q
R
Q
Q = O H O
A
H R = H, -CH3
I II  
 
Fig. 1 – Synthesis of glutamic acid and diols based polyesters 
using coupling agent DCC 
 
As amino group is more nucleophilic center than 
hydroxyl group, it was necessary to provide amino 
group protection. We optimized conditions of amino 
group blocking and deblocking, one can observe in Ta-
ble 1 protection groups and N-derivatives of glutamic 
acid which were used in this work. 
 
Table 1 – Protective groups and N-derivates of glutamic acid 
 
Tert-
butoxycarbonyl 
protective 
group  (Boc) 
O O
OHOH
NHO
O  
Acetyl pro-
tective 
group (Ac) 
OH
O
NH
O CH3
OH
O  
Trifluoroacetyl 
protective 
group (TFA) 
O O
OHOH
NH
O
F
F
F
 
N-stearoyl 
glutamic 
acid 
 
 
Accept reaction of peptide bond formation, other 
side reactions influence on the reaction selectivity – 
cycle esters formation and rearrangement of active 
ester according to fig.2. 
 
 O O
O
N
C N
O H
ANH
C NO
O O
O
A
rearrangement
 
 
Fig. 2 – Rearrangement of active ester of glutamic acid and 
DCC to passive amide  
OH OH
O
NH
O
O CH2 CH316
 S.M. VARVARENKO, N.V. PUZKO, A.S. VORONOV , ET AL. PROC. NAP 1, 01NDLCN13 (2012) 
 
 
01NDLCN13-2 
The running of these reactions was confirmed by 
mass spectroscopy. These reactions have significant 
effect on the polycondensation degree, but optimal pro-
cess conditions for maximal suppression of these reac-
tions were ascertained. Furthermore, it is well known 
[4], it’s necessary to introduce nucleophilic additives in 
reaction mixture to achieve high conversion. On prac-
tice 4-dimethylaminopyridine (DMAP) is widely used. 
It turned more efficient in comparison with 1,4-
diazabicyclo[2.2.2]octane (DABCO) and triethylamine. 
Polycondensation was successfully conducted using 
N-stearoyl glutamic acid, glutamic acid with acetyl pro-
tective group and diols in the range of molecular mass 
100-2000 Da. Polycondensation degree made 75-85% of 
maximal calculated one. Using glutamic acid with tert-
butoxycarbonyl protective group, we obtained polyesters 
with polycondensation degree 1-3. We didn’t succeed to 
obtain polyesters based on ethyleneglycol and propyl-
eneglycol, the same as we didn’t obtain polymers with 
terminal carboxyl groups (fig. 1, Q=I).  The first can be 
explained by high probability of cyclization reaction for 
these alcohols. The second – by side reaction of rear-
rangement of active ester, therefore the reaction should 
be conducted in the condition of alcohol excess.  
Hereby, developed method was used for synthesis of 
polymers, containing hydrophilic (polyethyleneglycol) 
and lipophilic (polypropyleneglycol and N-stearoyl glu-
tamic acid) fragments. Hydrophilic-lipophillic balance 
of such polymers can be controlled by different frag-
ments ratio and polyethyleneglycol and polypropyl-
eneglycol molecular mass. Polymer structure was con-
firmed by NMR- and IR-spectroscopy, molecular mass 
was determinated by gel-penetrative chromatography.   
  
3. SURFACE-ACTIVE AND COLLOIDAL PROP-
ERTIES OF  GLUTAMIC ACID BASED POLY-
ESTERS  
 
Colloidal and chemical properties of obtained poly-
esters strongly depend on their composition. Thus poly-
esters co-Glu(HCl)-co-PEG or co-Glu(HCl)-co-PPG (the-
se polyesters are formed after co-Glu(Boc)-co-PEG and 
co-Glu(Boc)-co-PPG deblocking, molecular mass of PEG 
and PPG – 100-600 Da) are water soluable. Water solu-
tions of such polymers don’t posses colloid-chemical 
properties even at high polymer concentration. 
 Co-Glu(St)-co-PEG or co-Glu(St)-co-PPG type poly-
mers with the same molecular mass of PEG and PPG are 
water insoluble, they are not able to form stable self-
stabilized dispersions in water and haven’t ability to de-
crease surface tension on water-air interface. Only co-
Glu(Ac)-co-DEG (synthesized via polycondensation of 
Glu(Ac) and diethylenglycol (DEG))  among this type of 
polymers shows significant surface activity and self-
stabilized water dispersions. This copolymer forms stable 
water dispersion with surface tension 47-49 mN/m. The 
last demonstrates that surface-active properties and 
properties of water dispersion self-stabilization can be 
achieved via hydrophilic/lipophilic fragments ratio in pol-
ymer chain. In this work polyesters with necessary prop-
erties were obtained due to forming of polymers with 
complex architecture. Thus Glu(St) based polyesters were 
obtained using mixture of  equal molar quantities of PEG 
and PPG of different molecular mass as diol (Fig. 3).   
 
mn
k
OO
O O
OH
NH
O
CH3
CH
3
O
O
O O
NH
O
CH3  
 
Fig. 3 – Schematic structure of polyester synthesized via poly-
condensation of Glu(St) and mixture of  equal molar quanti-
ties of PEG and PPG  
 
Two different diols and their part in macromolecule 
structure were confirmed by NMR-spectroscopy. Large 
majority of polyesters with different diols posses ability 
to form self-stabilized water dispersion. Such polyes-
ters show higher surface activity than polyester mole-
cules with one type of alcohol (fig. 4). 
 
20,00
30,00
40,00
50,00
60,00
70,00
80,00
S
u
rf
a
ce
 t
e
n
si
o
n
, 
m
N
/m
Polyesters synthesized 
using one type of diols
Precursor-based polyesters
Polyesters synthesized 
using two type of diols
 
 
Fig. 4 – Surface-active properties of polyesters synthesized 
via different methods 
 
Though, entering of diols of different structure in 
polymer macromolecule is not equivalent, it leads to 
irregular block structure and significant nonuniformity 
of functional distribution. In this case control of sur-
face-active and colloidal properties of polyesters with 
different fragments is realized incompletely. In this 
case, should expect that regular sequence of blocks of 
different nature allows to achieve higher surface activi-
ty. Polyester synthesis with regular block sequence 
conducted via prior precursor synthesis with the follow-
ing structure: 
 
 
n
16 16
OO
OH
O CH2 CH3
O
NH
O
OOH
O
R NH
O CH2 CH3
 
 
Fig. 5 – Structure of precursor used for polyester synthesis 
with regular block sequence. In the case R=H – Glu(St)-PEG-
Glu(St),  R=CH3 – Glu(St)-PPG-Glu(St) 
 
Synthesized precursors according to their nature 
are dicarboxylic acids consisting of glutamic acid resi-
due bonded by polyoxypropilene(polyoxyethylene) 
 COLLOIDAL AND CHEMICAL PROPERTIES OF POLYESTERS … PROC. NAP 1, 01NDLCN13 (2012) 
 
 
01NDLCN13-3 
chains with different molecular mass. Such precursors 
were used for polyester synthesis according to the 
scheme on Fig. 1 instead of glutamic acid or its deriva-
tives. NMR-spectroscopic study confirmed precursors 
structure and showed that 83-87% of portal carboxyl 
groups are γ-carboxyl groups. It facilitates reaction in 
comparison with glutamic acid or its derivatives due to 
the carboxyl group reactivity equalization. For pseudo-
poly(amino acid)s synthesis we used precursors with 
PPG in the range of molecular mass 130-1000 Da. Ob-
tained polyesters have the same structure as polyesters 
synthesized using mixture of equal molar quantities of 
PEG and PPG, but differ by strict regular structure. 
This fact was confirmed by NMR-spectroscopy. As ex-
pected, polyesters with regular molecules structure 
posses more strongly pronounced surface-active proper-
ties (Fig. 4). More over conducted studies show that 
majority of precursor-based polymers hane complex 
type of surface tension isotherm with strongly pro-
nounced two breaking points (Fig. 6). 
 
20,00
30,00
40,00
50,00
60,00
70,00
80,00
0,00 0,10 0,20 0,30 0,40
S
u
rf
a
ce
 t
e
n
si
on
, m
N
/m
Polymer concentration, %
4. (Glu-St—PPG1000—Glu-St)--PEG400
20,00
30,00
40,00
50,00
60,00
70,00
80,00
0,00 0,05 0,10 0,15 0,20
S
u
r
fa
c
e
 t
e
n
s
io
n
, m
N
/m
Polymer concentration, %
3. (Glu-St—DPG—Glu-St)--PEG400
20,00
30,00
40,00
50,00
60,00
70,00
80,00
0,00 0,10 0,20 0,30 0,40 0,50
S
u
rf
a
ce
 t
e
n
si
o
n
, 
m
N
/m
Polymer concentration, %
2. (Glu-St—PPG400—Glu-St)--PEG400
20,00
30,00
40,00
50,00
60,00
70,00
80,00
0,00 0,02 0,04 0,06 0,08 0,10 0,12 0,14
S
u
rf
a
ce
 t
e
n
si
o
n
, 
m
N
/m
Polymer concentration, %
1. (Glu-St—PPG400—Glu-St)--PEG300
 
 
Fig. 6 – Surface tension curves of selected precursor-based 
polyesters 
 
The first breaking point (starting from coordination 
zero) has to be considered as critical micelle concentra-
tion (CMC) (CMC values of few polymer samples are 
given in Table 2).  
 
Table 2 – Selected characteristics of precursor-based polyesters 
 
№ 
Polyester based on 
(Glu-St—DPG—Glu-St) 
precursor C
M
C
1
%
 
C
M
C
2
 %
 
M
o
le
cu
la
r 
m
a
ss
(a
cc
o
r-
d
in
g
 t
o
 G
P
C
) 
H
L
B
 
1 
Glu-St—DPG—Glu-St-- 
PEG400 
0,0042 0,0337 2980 9,4 
2 
Glu-St—DPG—Glu-St-- 
PEG600 
0,0051 0,0532 3405 13,7 
 
Precursor-based polyesters form self-stabilized pol-
ymer dispersions with unimodal nanometer disperse 
phase distribution at negligibly higher concentration 
than CMC (Fig. 7.) 
 
Polymer concentration increasing in water disper-
sion leads to complex but organized dispersed phase 
rearrangement. This fact is displayed by the second 
breaking point on the surface tension isotherm curve. 
Furthermore, particle size distribution curve also has 
dependence on the polymer concentration (Fig. 7). Pre-
sented data shows some average diameter increase of 
dispersed phase first mode with polymer concentration 
increase. Simultaneously, one can observe formation of 
the second mode particles (approaching the second 
breaking point concentration on the surface tension iso-
therm curve) and the third mode particles formation at 
the concentration higher than the second breaking point 
concentration on the surface tension isotherm curve. 
 
 
 
Fig. 7 – Characteristic distribution curve obtained using DLS 
method 
 
The character of particle distribution changing indi-
cates on the formation of disperse phase particle of com-
plex structure with regions of different properties due to 
the hydrophilic and lipophilic fragments in polyester 
molecules. This conclusion is confirmed by solubilization 
curves of insoluble organic substances. Toluene and su-
dan (III) solubilization curves is presented on Fig. 7.  
Noticeable solubilization of sudan is observed under 
CMC. As about toluene solubilization – it can be ob-
served at concentration higher than the second break-
ing point concentration on the surface tension isotherm 
curve. Thus, regions able to solubilize toluene in dis-
perse phase can be formed at concentration higher than 
the second breaking point concentration on the surface 
tension isotherm curve. One can observe disperse 
phase particle formation of the second and third mode 
on the size distribution curve.  
 
 S.M. VARVARENKO, N.V. PUZKO, A.S. VORONOV , ET AL. PROC. NAP 1, 01NDLCN13 (2012) 
 
 
01NDLCN13-4 
0,00E+00
1,00E-05
2,00E-05
3,00E-05
4,00E-05
5,00E-05
6,00E-05
7,00E-05
8,00E-05
9,00E-05
1,00E-04
0 0,02 0,04 0,06 0,08 0,1 0,12 0,14 0,16 0,18 0,2 0,22
g
 d
y
e
 /
m
l
s
o
lu
ti
o
n
Polymer concentration, %
Sudan (III) solubilization
(GluSt-DPG-GluSt)--PEG-400
(GluSt-DPG-GluSt)--PEG-600
(GluSt-PPG-400-GluSt)--PEG- 300
GluSt-PPG-1000-GluSt)-- PEG-400
 
-1,0E-04
9,0E-04
1,9E-03
2,9E-03
3,9E-03
4,9E-03
0
0
,0
5
0
,1
0
,1
5
0
,2
0
,2
5
0
,3
0
,3
5
0
,4
0
,4
5
0
,5
0
,5
5
0
,6
0
,6
5
0
,7
0
,7
5
0
,8
0
,8
5
0
,9
0
,9
5 1
1
,0
5
g
 t
o
lu
e
n
e
 /
m
l 
s
o
lu
ti
o
n
Polymer concentration, %
Toluene solubilization
(GluSt-DPG-GluSt)--PEG-400
(GluSt-PPG-400-GluSt)--PEG-
300
(GluSt-DPG-GluSt)--PEG-400
(GluSt-PPG-1000-GluSt)--PEG-
400
(GluSt-PPG-1000-GluSt)--PEG-
400
(GluSt-DPG-GluSt)--PEG-600
 
 
Fig. 8 – Curves of toluene and water insoluble dye Sudan (III) 
solubilization 
4. CONCLUSIONS  
 
Novel polyesters based on glutamic acid (or its de-
rivatives) and diols of polyoxyethylene/ polyoxypropyl-
ene type were synthesized. Developed technique allows 
to obtain polyester with different hydrophilic-lipophillic 
balance using the ratio of hydrophilic/lipophillic frag-
ments in polyester molecules. The structure and com-
position of synthesized polymers were confirmed using 
NMR, IR-spectroscopy, molecular mass was settled via 
gel-penentration chromatography. Such polyester pos-
ses surface-active properties, and are able to form self-
stabilized water dispersion. These dispersions solubil-
ize water insoluble compounds. Thus obtained polyes-
ters are promising materials for formation of dispersed 
drug delivery systems. 
 
 
 
 
  
 
REFERENCES 
 
1. I.A. Trail, E.S. Powell, J. Noble, J. Hand Surg.-Brit. Eur. 
14, No4, 422 (1989). 
2. D.L. Wise, H. Rosenkrantz, J.B. Gregory, H.J. Esber, J. 
Pharm. Pharmacol. 32, 399 (1980). 
3. J. Kohn, R. Langer, Polym. Mater. Sci. Eng. 51, 119 
(1984). 
4. B. Neises, W. Steglich, Angew. Chem. Int. Ed. 17, 522 (1978).
 


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Colloidal and Chemical Properties of Polyesters Based on Glutamic Acid and Diols of Different Nature

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