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Biocompatible Catalysts for Lactide PolymerizationCatalyst

Activity, Racemization Effect, and Optimization of the
Polymerization Based On Design of Experiments
Agnieszka Gadomska-Gajadhur and Paweł Ruśkowski*

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ABSTRACT: An original synthesis of Ca, Mg, and Zn 2-ethylhexanoate (octoate) obtained by reaction between metallic powder
with 2-ethylhexanoic acid was achieved. The activities of obtaining biocompatible catalysts of lactide polymerization were tested.
Downloaded via 58.27.233.69 on September 6, 2022 at 04:39:46 (UTC).

The most active catalyst was zinc 2-ethylhexanoate (ZnOct2), and the lowest activity catalyst was calcium 2-ethylhexanoate
(CaOct2). The ROP process was successfully optimized by using the design of the experiment. Polylactide with Mw = 82.3 kg/mol
with lactide conversion up to 85% and 8% content of D-lactic acid has been obtained. Thus, the obtained polylactides can be used in
medical and pharmaceutical devices.
KEYWORDS: PLA, racemization, medical devices, DOE, scale-up

■ INTRODUCTION
Polylactide is a “double green” polymer with high application
chains creates stereocomplexes with a melting point of
approximately 230 °C.27,28
potential.1,2 Raw materials for its production can be obtained Mechanical properties characterize materials made of PLA.
from renewable resources.3 After using the product, it can be It can be a soft and flexible or hard and durable plastics.29 For
composted, where it decomposes into nontoxic products (CO2 homochiral PLA, as the average molar mass increases, the
and H2O).4 Nontoxic and biocompatible PLA can be used in flexural strength increases, and the tensile strength does not
regenerative medicine for damaged tissues. Also, PLA has change.30 However, as the PLDLA average molar mass
found many applications: packaging materials,1,5 textiles,6 and increases, the flexural and tensile strength increases.31
Polylactide with strictly defined chirality can be obtained
composites.68 Medicine7,8 and pharmacy9,10 are continually
looking for new applications for polylactide. Researchers have using optically active catalysts or mixtures of D,D-lactide and
focused on developing new forms of drug-delivery systems L,L-lactide with defined stoichiometry.32 The cost of
purchasing D,D-lactide is about twice as high as L,L-lactide.33
(DDS) and developing materials for regenerative medi-
cine.11−15 The price of meso-lactide is challenging to determine because
The monomer in PLA is lactic acid (LAc) (Scheme 1). It is a there are no suppliers of this raw material.34 Therefore, many
weak, water-soluble organic acid with an asymmetric carbon groups are working on catalysts that racemize lactide in situ in
atom.16 Lactic acid may exist in the form of two enantiomers: polymerization.35
D-(−)-LAc or L-(+)- LAc. L-(+)- LAc is present in living Direct lactic acid condensation on tin or zinc oxide leads to
organisms as a product of various metabolic changes.17 Lactic PLA under 5 kg/mol.36 High-molecular-weight PLA is
acid can be obtained as a result of chemical synthesis and obtained by ring-opening polymerization (ROP).37 The most
biotechnological methods.18,19 popular catalyst is tin(II) 2-ethylhexanoate (SnOct2).38 The
In chemical synthesis, a racemic LAc mixture is obtained. high-molecular-weight polymer (Mw> 100 kg/mol) is obtained
Biotechnologically, however, both optically active enantiomers with high lactide conversion (>95%)39,40 (Scheme 2).
can be selectively obtained as a result of bacterial (e.g., using The production of PLA with tin(II) catalysts41,42 disqualifies
the Lactobacillus strain20−22) fermentation of starch and other such obtained material from medicinal applications. Acceptable
carbohydrates derived from corn, sugar beet, or potatoes.23 content of tin(II) residue in medical devices should not exceed
The properties of PLA depend on the stereochemical 20 ppm of tin.43 The practical exclusion of tin content in
composition of the repeat units and their distribution along the
chain.24 Homochiral PLA (PLLA or PDLA) (Figure 1) is an Received: April 1, 2020
isotactic, stereoregular and semicrystalline polymer (degree of Published: July 13, 2020
crystallization up to 40%), with Tg 55−65 °C and Tm 170−183
°C.25 Atactic PLA is made of heterochiral PLDLA units. It is
an amorphous polymer with Tg = 59 °C, without melting
point.26 A mixture of homochiral, isotactic PLLA, and PDLA

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Scheme 1. Synthesis of Chiral Lactic Acid and Chiral Lactide

The latest trend in catalyst synthesis is the use of molecules

found in metabolic pathways (i.e., magnesium,52,53 zinc,54−60
and calcium).61,62 To date, scientists have developed dozens of
catalysts based on zinc.54−60 Unfortunately, their use leads to
low-molecular-weight PLA (Mw < 15 kg/mol). Less scientific
work concerns catalysts of magnesium and calcium.52,53
Polymerizations catalyzed with Ca and Mg salts have a long
time of reaction (1−4 days) and polymer molar mass under 13
kg/mol.
Our research aimed to find new nontoxic catalysts for lactide
polymerization. The next step was to examine the activity of
Figure 1. Chemical structure of polylactide, stereochemistry, and the catalysts and determine optimal reaction conditions.43
properties. Additionally, we checked whether racemization of the chiral
center in lactic acid occurs because of the use of strongly basic
Scheme 2. Synthesis of Polylactide with Tin(II) Octoate metals in catalysts.
Presently the most effective ROP catalyst is SnOct2. We
tried to obtain its magnesium, zinc, and calcium analogue
MOct2 (M is metal).
Several methods can obtain magnesium (calcium or zinc)
octoate (4). The first method is the reaction between 2-
ethylhexanoic acid (3) and a metal oxide.63,64 The water
formed in the reaction is azeotropically separated. The second
method is the reaction between metal chloride65,66 and 2-
medical devices is a premise to research the search for new ethylhexanoic acid (3). In this reaction, hydrogen chloride is
biocompatible catalysts for lactide polymerization.44−47 formed in addition to the desired catalyst. The presence of
In the synthesis of medical PLA, it is recommended to use hydrogen chloride is unfavorable because of its strong
zirconium48 and titanium49−51 catalysts. Zirconium and corrosive effect on the steel apparatus.
titanium are used for production of bone implants, so they We used the design of experiments to optimize process
should also be nontoxic to humans in other applications.
However, it has been found that some people may have an conditions. Three variables in the rotatable factorial plan were
allergic reaction. Zr and Ti catalysts are more expensive than examined. We tested the significance of the equation
the commonly used SnOct2, which increases the cost of PLA coefficients with the Student’s t-test. The MS Solver add-on
production. predicted the optimal conditions of polymerization.67
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pubs.acs.org/OPRD Article

EXPERIMENTAL SECTION Product was obtained with 87% yields (10.4 g, 0.03 mol)
All solvents (toluene, dichloromethane) and other reagents and 99.5% purity.47
(magnesium, zinc, calcium) were used without any purifica- ZnOct2. The product was a transparent syrup; IR (ATR,
tion. cm−1): 2962, 2933, 1628, 1592; 1H NMR (400 MHz, DMSO-
L,L-Lactide (Boehringer Company) with high purity d6) δ/ppm: 0.80 (m, 6H) 1.23 (m, 4H) 1.35 (m, 2H) 1.45 (m,
>99.5%, water content <80 ppm, and content of free acids 2H) 2.02 (dq, 1H); elemental analysis (%): calcd C 54.62; H
under 0.3 mmol/kg was used. IR spectra were measured using 8.59; anal. C 54.63; H 8.62.
a BRUKER ALPHA II Platinum ATR spectrometer (in ATR Polymerization of L-Lactide. L-Lactide (8.64 g, 0.06
technics). 1H or 13C NMR spectra were measured using a mol) was melted in an argon atmosphere with magnetic
Mercury-400BB spectrometer (400 MHz). Elemental analysis stirring (160 rpm) in a temperature range from 120 to 200 °C
was measured by PerkinElmer, model PE Seria II CHNS/O. A (start of polymerization). 0.06−0.7 mL of 0.12 M solution of
gel permeation chromatography measured molecular weights catalyst (MgOct2, CaOct2, ZnOct2) in CH2Cl2 was added
of PLA samples. The apparatus UltiMate 3000 Dionex, with (0.05−1.5%mol. catalyst/lactide ratio). Reactions were carried
refractometric detector RIn-101 Shodex and with two Jordi out in t = 1−32 h. The reaction products were cooled down to
Gel DVB Mixed Bed columns was used. Conversion of lactide room temperature in an argon atmosphere and analyzed.
was predicted using the calibration curve method. Polylactides were obtained with the conversion of lactide 2−
The specific rotation of the product was measured with a 98.0% and Mw 1.2−34.1 kg/mol, DI 1.4−2.4, %D 0−13%.
polAAr 32 automatic polarimeter. PLA. The product was a white or yellow solid; IR (ATR,
The content of D centers in the PLA chain was calculated cm−1): 1749, 1181, 868; 1H NMR (400 MHz, CDCl3) δ/ppm:
from the formula: 1.54 (d, 3H) 5.18 (q, 1H); 13C NMR (100 MHz, CDCl3) δ/
ppm: 16.7; 20.5, 52.3, 69.0, 170.3
%D =
[α ] + α w
2 · αw
·100%
■ RESULTS AND DISCUSSION
Synthesis of Catalysts. The catalyst synthesis was carried
where: % D - the percentage of centers -D; [α] - specific out in the direct reaction of an acid (3) with metal (Scheme
rotation of the tested polymer αw - specific rotation of poly-D- 3). The merit of this method is the lower price of metal than its
lactide (+161.0°) oxide or chloride. The second reaction product is hydrogen,
Synthesis of Calcium 2-Ethylhexanoate (CaOct2, 4a). which is removable from the reaction mixture.47
2-Ethylhexanoic acid (11 mL, 10 g, (0.07 mol)), pellets of
calcium (1.40 g, 0.035 mol, the particle size of calcium <5 Scheme 3. Obtaining of Calcium, Magnesium, and Zinc 2-
mm), and toluene (70 mL) were agitated (200 rpm) and Ethylhexanoate
heated under reflux for 24 h. Unreacted calcium was filtered
out from the hot solution. Product was filtered at room
temperature and washed with toluene (15 mL).
Product was obtained with 64% yields (7.3 g, 0.022 mol)
and 95.3% purity.47
CaOct2. The product was a white solid; IR (ATR, cm−1):
2962, 2936, 1685, 1561; 1H NMR (400 MHz, DMSO-d6) δ/
ppm: 0.82 (2t, 6H) 1.22 (m, 4H) 1.28 (m, 2H) 1.45 (m, 2H)
1.87 (s, 1H); elemental analysis (%): calcd C 58.86; H 9.26; The reaction between acid 3 with metal was carried out in
anal. C 59.87; H 9.22. reflux of toluene. The substrates were mixed using a magnetic
Synthesis of Magnesium 2-Ethylhexanoate (MgOct2, stirrer for 8−24 h (yield 64−87%). The viscosity of the
4b). 2-Ethylhexanoic acid (22 mL, 20 g, (0.14 mol), powdered reaction mixture acid 3 to metal in molar ratio 2:1 was too
magnesium (1.68 g, 0.07 mol, the particle size of magnesium high. To reduce them, it was necessary to add an appropriate
<5 μm), and toluene (100 mL) were agitated (200 rpm) and volume of toluene. This treatment allowed for better mixing of
heated under reflux for 20 h. Unreacted magnesium was the reaction mixture in the final stage of the process. The
filtered out from the hot solution. Product was filtered at room unreacted metal particles were selectively separated by hot
temperature and washed with toluene (15 mL). filtration. The yellow product is crystallized from the toluene
Product was obtained with 80% yields (17.4 g, 0.11 mol) solution at room temperature. Then it could be separated by
and 99.8% purity.68 subsequent filtration. The last step was washing a product with
MgOct2. The product was a yellow solid; IR (ATR, cm−1): toluene and drying at room temperature. The catalyst was
2960, 2934, 1692, 1603; 1H NMR (400 MHz, DMSO-d6) δ/ obtained with sufficient good purity. The most important
ppm: 0.84 (m, 6H) 1.26 (m, 4H) 1.59 (m, 4H) 1.89 (m, 1H); feature was the low content of water (<400 ppm). The
13
C NMR (100 MHz, DMSO-d6) δ/ppm: 12.1; 14.0; 22.8; presence of water in the catalyst is disadvantageous because it
25.4; 29.7; 31.8; 47.6; 183.9; elemental analysis (%): calcd C cannot be used for ring-opening polymerization (Table 1).
61.8; H 9.73; anal. C 61.5; H 9.71. Catalysts Activity in Lactide Polymerization. L-LD
Synthesis of Zinc 2-Ethylhexanoate (ZnOct2, 4c). 2- polymerization was provided out at 200 °C for 24 h with
Ethylhexanoic acid (11 mL, 10 g, (0.07 mol)), powder of zinc 0.05%mol catalyst (Figure 2.). The lowest LD conversion was
(2.246 g, 0.034 mol, the particle size of zinc <1 μm), and obtained with a calcium catalyst (58%). The conversion at the
toluene (70 mL) were agitated (200 rpm) and heated under same high level (92%) was achieved in the case of magnesium
reflux for 8 h. Unreacted zinc was filtered out from the hot (91.5%) and zinc (92.8%) catalysts. The lowest molecular
solution. Product was filtered at room temperature and washed weight, 19.5 kg/mol, was obtained against CaOct2. The
with toluene (15 mL). polylactide obtained against MgOct2 had an average molar
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Table 1. Results of Synthesis of Calcium, Magnesium, and Zinc Octoate

2-ethylheksanoate time (h) yields (%) purity (%) water content (ppm)
zinc 8 87.0 99.5 350
magnesium 20 80.0 99.8 280
calcium 24 64.0 95.3 300

Figure 2. Influence of catalyst on lactide conversion and molecular

weight.

mass of about 31 kg/mol. The highest molar mass (64 kg/mol)

was obtained in a ZnOct2-catalyzed reaction.
Racemization of Lactide in ROP. Two methods
determined the degree of racemization of lactic acid in
polylactide. The signal surface ratio of 169.3 ppm (heterochiral
PLA) to 169.5 ppm (homochiral PLA) was determined in the
13
C NMR spectrum (Figure 3, Table 2).
Optimization of L,L-Lactide Polymerization. High
conversion of lactide in PLA is necessary for the material to
be used in medicine. When residual lactide concentration in Figure 3. Fragment of 13C NMR spectrum of polylactides obtained
PLA is high, additional steps to remove it are required. This against SnOct2 (blue), CaOct2 (green), MgOct2 (red) (169.3 ppm −
prolongs the process and increases its cost.69−71 The molecular PDLLA, 169.5 ppm - PLLA)
weight of PLA significantly affects the potential application.
The higher Mw PLA is used for implants, and the lower Mw Table 2. Degree of Racemization of Lactic Acid in PLA
PLA is used for DDS. Thus, it seems useful to link the Determined by 13C NMR and Specific Rotation
synthesis conditions to Mw of the polymer. The content of D Measurement
centers in PLA (% D) should not exceed 15%.72 racemization degree of lactic acid, %
Essential process variables were checked (e.g., temperature 13
catalyst C NMR specific rotation
and reaction time, catalyst concentration, and mixing
efficiency). During polymerization, it is challenging to keep SnOct2 0 0
the mixing speed constant. A significant increase in viscosity CaOct2 32.0 31.9
during the process is responsible for this effect. So we MgOct2 20.3 20.8
established this variable at a constant level. The quality of the ZnOct2 14.5 13.9
L,L-lactide substrate used in the reaction determines the
molecular weight of the polymer. Too high water content The criteria of optimization were to maximize of conversion of
(>150 ppm) and/or lactic acid decrease a molecular weight of lactide (ŷ1) and molecular weight of polylactide (ŷ2). The
PLA. Before each reaction, the content of water and free acids percentage of the content of D centers in PLA should be below
in the lactide was tested.68 15%, ŷ4. We tested the effect of the time z1 (1.3−4.7 h),
The optimization carried out was to indicate a relationship catalyst/LD ratio z2 (0.08−0.42%mol), and reaction time z3
of lactide conversion (ŷ1) and average molecular weight (Mw) (143.2−176.8 °C) (Table 3).
(ŷ2) and content of D centers in PLA (%D) (ŷ4) on reaction A rotatable 20-run design was used. This plan contains a 2-
time (z1), catalyst concentration (z2), and temperature (z3), level factorial part (eight runs with three input variables at all
respectively. The second-degree equation can be obtained combinations of the +1 and −1 levels). The next part is a star
using a rotatable compositional plane: points (six runs with each of the three input variables at
−1.682 and +1.682, while the other two were at (0)). The last
yi ̂ = b0 + Σbixi + Σbijxixj + Σbixi 2
is replicates at the center of the design (six runs with all three
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Table 3. Polymerization of L-Lactide with ZnOct2. Factorial 23 and Rotatable Designs: Variables at Maximum and Minimum
Levels
xi natural variable (−1.682) (−1) (0) (+1) (+1.682)
x1 time (h) 1.3 2.0 3.0 4.0 4.7
x2 catalyst/LD ratio (%mol) 0.08 0.15 0.25 0.35 0.42
x3 temperature (°C) 143.2 150 160 170 176.8

Table 4. L-Lactide Polymerization with ZnOct2. Factorial Rotatable Design: Experimental Matrixa and Resultsb
coded variables conversion (%) Mw (kg/mol) Mn (kg/mol) %D (%)
no. x1 x2 x3 y1 ŷ1 y2 ŷ2 y3 y4 ŷ4
1 −1 −1 −1 25.6 26.4 58.1 53.7 42.9 11.0 10.6
2 +1 −1 −1 77.4 71.0 69.6 70.3 39.0 5.5 6.6
3 −1 +1 −1 48.3 40.5 50.5 49.9 35.5 4.9 4.7
4 +1 +1 −1 81.6 85.2 61.9 66.5 37.4 3.7 3.6
5 −1 −1 +1 30.4 26.1 33.9 30.5 31.4 2.2 2.9
6 +1 −1 +1 57.2 60.0 43.4 47.2 22.2 3.3 4.1
7 −1 +1 +1 45.6 47.0 27.7 34.3 19.9 3.9 3.4
8 +1 +1 +1 82.4 80.9 49.3 50.9 24.3 6.5 7.5
9 −1.682 0 0 19.3 23.0 13.8 16.2 12.8 3.2 3.4
10 +1.682 0 0 90.3 89.0 49.3 44.2 25.4 4.5 3.4
11 0 −1.682 0 34.0 37.4 59.8 65.6 28.2 3.6 2.6
12 0 +1.682 0 65.2 66.9 73.0 65.6 44.8 0.3 0.5
13 0 0 −1.682 50.5 57.9 73.2 74.3 49.9 12.8 12.9
14 0 0 +1.682 51.7 54.1 45.5 41.7 30.8 10.6 9.7
15 0 0 0 55.5 56.0 67.4 65.6 34.1 4.7 4.8
16 0 0 0 55.9 56.0 65.4 65.6 36.9 5.1 4.8
17 0 0 0 56.8 56.0 68.7 65.6 37.5 4.8 4.8
18 0 0 0 57.3 56.0 64.6 65.6 32.5 4.7 4.8
19 0 0 0 53.7 56.0 62.5 65.6 32.4 4.9 4.8
20 0 0 0 57.7 56.0 64.7 65.6 36.5 4.4 4.8
a
Constant conditions: all experiments were performed using the same raw materials; scale: 8.64 g (0.06 mol) of L-lactide (purity >99.5%, contents
of water <80 ppm and free acids 0.3 mmol/kg; stirring rate 160 rpm, in an argon atmosphere. bAll ŷi have been calculated from the quadratic
model.

variables at 0). In all experiments, the remaining variables were

constant (Table 4). The experiments were performed in
random order, and for each experiment, all four of the response
variables, yi, were measured. Table 4 shows the design matrix,
along with the measured responses.
To shorten the discussion, without the statistical analysis
details are presented in this paper. We present here only the
selected quadratic models (without insignificant coefficients)
and the most important diagrams.
Conversion of Lactide, ŷ1 (%).

y1̂ = 56.0 + 19.6x1 + 8.77x 2 − 1.12x3 − 2.69x1x3

− 1.69x 2x3 − 1.37x 2 2
Figure 4. L-Lactide conversion (ŷ1) as an effect of the reaction time
Figure 4 shows the effect of conversion of lactide; ŷ1 depends (x1), and concentration of catalyst, (x2); temperature (x3) = +1.
on the reaction time x1 and catalyst concentration x2, at the
reaction temperature x3 = +1. y4̂ = 4.79 − 0.63x 2 − 0.94x3 + 0.73x1x 2 + 1.30x 2x3
Molecular Weight of PLA (Mw) ŷ2, (kg/mol).
+ 1.60x 2x3 − 0.49x12 − 1.16x 2 2 + 2.29x32
y2̂ = 65.6 + 8.32x1 − 9.69x3 + 1.88x 2x3 − 12.5x12
Figure 6 shows the content of D centers in PLA (%D) (ŷ4)
− 2.69x32 depends on the catalyst concentration x2 and temperature x3,
at the reaction time x1 = +1.
Figure 5 shows the PLA molecular weight (ŷ2) depends on the The experimental data was described very well by the
reaction time (x1) and temperature (x3), at the catalyst obtained equations. An optimal point was calculated using the
concentration x2 = +1. Microsoft Solver. The optimization criteria were to obtain the
Content of D Centers in PLA (%D) (ŷ4). maximum molar mass with lactide conversion >80% with the
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Table 6. Obtained Results of L-Lactide Polymerization at

Different Scales
scale LD mass (g) conversion (%) Mw (g/mol) %D (%)
lab 8.64 85.0 82.3 8.4
large lab 52.0 85.9 81.9 8.6
production 1300 89.2 86.9 9.6

The scale was increased 25 times. The experiment was

carried out at 2 L metal reactor. This apparatus can be used on
a postproduction medical PLA scale. The same proportions
were tested as on the large laboratory scale. The results that
were obtained also matched very well to those of smaller scales
(lab and large laboratory). A polymer with a high 89.2%
conversion and a higher molecular weight of 86.9 kg/mol was
Figure 5. Polylactide molecular weight (ŷ2) as a function of the obtained. The content of D centers (9.6%) was similar to the
reaction time (x1) and temperature (x3); catalyst concentration (x2) = one predicted by the optimization model. It can be concluded
+1. that the received models also work well on a larger scale
(Figure 7).

Figure 6. Content of D centers (ŷ4) as a function of the concentration

of catalyst (x2) and the temperature (x3); reaction time (x1) = +1

content of D centers <15%. The coordinates of the optimal Figure 7. Process scale-up diagram.
point are the following: z1 = 4.7 h, z2 = 0.08%mol, z3 = 176.8
°C. The result of the reaction under these conditions should be
a polymer with Mw = 81.1 kg/mol and conversion of 84.5%
and %D = 8%. The PLA with Mw = 82.3 kg/mol and 85.0%
conversion and %D = 8.4% (Table 5) was obtained in a ■ CONCLUSIONS
An original method for synthesis of biocompatible catalysts
Table 5. Experimental and Predicted Results of Polylactide was developed. It is based on the reaction of 2-ethylhexanoic
Synthesis with ZnOct2 in Optimal Conditions acid with metals (e.g., zinc, calcium, and magnesium). It was
results conversion (%) Mw (kg/mol) %D (%) shown that ZnOct2 is a very good, nontoxic catalyst for PLA
calculated 84.5 81.1 8.0 production. Adequate mathematical models (conversion of
experimental 85.0 82.3 8.4 lactide, PLA molecular weight, and contents of D centers in the
polymer) for lactide polymerization catalyzed by ZnOct2 were
confirmatory experiment. The obtained result, in line with the obtained. Polymerization conditions with ZnOct2 as catalyst
forecast, testifies to the correctness of the equations obtained. were developed. The PLA was obtained with 85% lactide
The average molar mass of polymers was increased from 20.0 conversion and an average molecular weight of 82.3 kg/mol,
up to 70.0 kg/mol.68 and D% = 8.4%, without tin(II) residues. The obtained models
Scale-up of Lactide Polymerization. In determining have been shown to work well, even when scaled-up.
optimal conditions, a large-scale laboratory process was carried Convergent results were obtained with a 6- and 25-fold
out at 50 g of lactide. The reaction conditions were as follows: increase in scale. It has been shown that the developed process
temperature, 175 °C; catalyst concentration, 0.08%; and conditions can be transferred to a production scale.

■
reaction time, 5 h. The reaction was conducted for 5 h. The
scale of the process has been increased six times (Figure 6). AUTHOR INFORMATION
The results were similar to those of optimization were
obtained. The conversion of lactide differed approximately Corresponding Author
1% (Table 6) and Mw by approximately 0.4 kg/mol. High Paweł Ruśkowski − Faculty of Chemistry, Warsaw University of
compliance was also observed on the content of D centers Technology, 00-664 Warsaw, Poland; orcid.org/0000-
(about 0.2%). 0002-4589-0727; Email: [email protected]
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Author (15) Wojciechowski, C.; Chwojnowski, A.; Dudziński, K.; Łukowska,

Agnieszka Gadomska-Gajadhur − Faculty of Chemistry, E. Evaluation of separation characteristic of polysulfone membranes
Warsaw University of Technology, 00-664 Warsaw, Poland; modified by polymer solvents etching. Desalin. Water Treat. 2011, 35,
orcid.org/0000-0001-7686-1745 263−270.
(16) Nagata, Y.; Kuroda, T.; Takagi, K.; Suginome, M. Ether
Complete contact information is available at: solvent-induced chirality inversion of helical poly (quinoxaline-2, 3-
https://pubs.acs.org/10.1021/acs.oprd.0c00149 diyl) s containing L-lactic acid derived side chains. Chem. Sci. 2014, 5,
4953−4956.
Notes (17) Klaenhammer, T. R. Bacteriocins of lactic acid bacteria.
The authors declare no competing financial interest. Biochimie 1988, 70, 337−349.

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(18) De Vuyst, L.; Leroy, F. Bacteriocins from lactic acid bacteria:
production, purification, and food applications. J. Mol. Micro.
ACKNOWLEDGMENTS Biotechnol. 2007, 13, 194−199.
Financial support obtained from Warsaw University of (19) Kavitake, D.; Kandasamy, S.; Devi, P. B.; Shetty, P. H. Recent
Technology, Faculty of Chemistry, is gratefully acknowledged. developments on encapsulation of lactic acid bacteria as potential

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starter culture in fermented foods−A review. Food Biosci. 2018, 21,
34−44.
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