Supporting information
Drugs as matrix to detect their own drug delivery system of
mPEG-b-PCL block copolymers in matrix-assisted laser
desorption/ionization- time of flight mass spectrometry
Katrin Knop,1,2 Steffi Stumpf,1,2 and Ulrich S. Schubert1,2*
1
Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena,
Humboldtstrasse 10, 07743 Germany
2
Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 8, 07743
Germany
*
Author for correspondence: Prof. Dr U. S. Schubert. Telephone: +49(0) 3641 948200,
Fax: +49(0) 3641 948202, E-mail: ulrich.schubert@uni-jena.de, Internet: www.schubert-group.com
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Synthesis of Poly(ethylene glycol)-block-poly(-caprolactone) (mPEG-b-PCL). The synthesis of
poly(ethylene glycol)-block-poly(-caprolactone) represents a standard procedure,[1–4] which was carried
out according to the following protocol. Briefly, 5 g (2.5 mmol) poly(ethylene glycol) 2 kDa was coevaporated with toluene prior to use. 2.11 mL (2.28 g, 20 mmol) -caprolactone and 40 µL (51 mg,
0.12 mmol) of tin-(II) ethylhexanoate, set to 1/20 of the initiating hydroxy groups, were added under
inert conditions. The reaction mixture was submitted to three freeze-pump-thaw cycles and,
subsequently, stirred overnight at 80 °C. The resulting highly viscous block copolymer was dissolved in
dichloromethane, precipitated into cold diethyl ether and dried in vacuo.
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H NMR (300 MHz, CDCl3):  4.20 (2H, t, PEG-CH2-O-CO), 4.03 (15H, m, PCL-CH2-O), 3.61
(176H, m, CH2-OH, O-CH2-CH2-O), 3.35 (4H, m, PEG-O-CH3 + carbon satellite), 2.28 (20H, m, COCH2), 1.62 (34H, m, COCH2-CH2-CH2CH2CH2O + COCH2CH2CH2-CH2-CH2O), 1.36 (17H, m,
COCH2CH2-CH2-CH2CH2O).
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Figure S1: (a) SEC traces of the mPEG and mPEG-b-PCL copolymers. (b) 1H-NMR spectrum of the
mPEG-b-PCL copolymer in CDCl3.
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Table S1. Overview of analytical data obtained for the mPEG-b-PCL copolymer.
Polymer
DP PCLa
Mn [g mol-1]a
1
mPEG-b-PCL
a
8
Mn [g mol-1]b
H NMR
SEC
2,900
1,700
PDI
Mn [g mol-1]c
PDI
MALDI
1.08
2,600
1.04
Calculated from 1H NMR. b Obtained from SEC (CHCl3:i-PrOH:TEA) using PEG calibration.
Obtained by MALDI-TOF MS.
c
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Figure S2: Determination of the critical micelle concentration for mPEG-b-PCL by means of (a) the
ratio of band I to band III of the fluorescence emission of pyrene, (b) the fluorescence intensity of the
pyrene fluorescence emission and (c) the intensity of the fluorescence emission of nile red.
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Determination of the cmc with pyrene. 1 mL of the polymer in acetone solution was dropped into
5 mL water under stirring to obtain the final concentrations between 1.0 × 10-3 mg mL-1 and 100 mg
mL-1. 10 µL of a 0.254 mg mL-1 concentrated pyrene in acetone solution was added leading to a final
pyrene concentration in water of 2.5 × 10-6 M. The acetone was evaporated for 2 days, the solutions
were refilled with water to 5 mL and the vials were closed to equilibrate for further 2 weeks. The
emission spectra were recorded between 350 nm and 500 nm with exc = 335 nm. Excitation spectra
were recorded from 300 nm to 380 nm. The emission wavelength was set to 390 nm.
Determination of the cmc with nile red. The aqueous polymer solutions were prepared in an analogue
way as described for the cmc determination with pyrene. To each sample, 10 µL of nile red in acetone
(0.4 mg mL-1) were added to result in a final nile red in water concentration of 2.5 × 10 -6 M. The
acetone was evaporated for 2 days and refilled to 5 mL and equilibrated for 2 weeks. The emission
spectra were recorded between 525 nm and 750 nm with exc = 520 nm.
The cmc was determined from the plotting to be 0.1 mg mL-1.
Synthesis of poly(2-ethyl-2-oxazoline) 2 kDa (PEtOx20). The PEtOx20 was synthesized according to
a reported procedure.[5,6] Briefly, the required amount of initiator (methyl tosylate, 37.3 mg, 0.2 mmol),
monomer (2-ethyl-2-oxazoline, 0.397 g, 0.413 mL, 4 mmol) and solvent (acetonitrile, 0.59 mL) were
transferred under argon into a flame-dried microwave vial. The reaction mixtures were heated under
microwave conditions to 140 °C for 190 s. The end capping was performed by adding 1 mL of
concentrated sodium carbonate solution by syringe to the microwave vials and stirring at room
temperature overnight. The reaction solution was diluted with dichloromethane, washed with aqueous
sodium hydrogen carbonate solution and brine, dried with sodium sulfate, filtered and dried under
vacuum. The repeating units were calculated by comparison of the signals at 6.06 ppm and 3.45 ppm.
1
H NMR (300 MHz, CDCl3):  3.43 (85H, m, N-CH2-CH2), 3.00 (3H, m, N-CH3), 2.32 (44H, m, CO-
CH2-CH3), 1.09 (68H, m, CO-CH2-CH3).
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Figure S3: (a) SEC traces of the PEtOx20 polymer. (b) 1H-NMR spectrum of the PEtOx20 polymer in
CDCl3.
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Table S2. Overview of analytical data obtained for the PEtOx polymer.
Polymer
DP PEtOxa
Mn [g mol-1]a
1
PEtOx20
a
21
Mn [g mol-1]b
H NMR
SEC
2,100
2,000
PDI
Mn [g mol-1]c
PDI
MALDI
1.14
2,200
1.04
Calculated from 1H NMR. b Obtained from SEC (CHCl3:i-PrOH:TEA) using PMMA calibration.
Obtained by MALDI-TOF MS.
c
8
Figure S4: Evaluation of the characteristic parameters of the MALDI-TOF MS spectra shown with
error bars on the basis of the maximum peak for mPEG 2 kDa as a function of the laser energy against
(a) the m/z value, (e) the intensity, (i) the S/N ratio, (m) the resolution. Evaluation of the characteristic
parameters of the MALDI-TOF MS spectra on the basis of the maximum peak for PMMA 2.5 kDa as a
function of the laser energy against (b) the m/z value, (f) the intensity, (j) the S/N ratio, (n) the
resolution. Evaluation of the characteristic parameters of the MALDI-TOF MS spectra on the basis of
the maximum peak for PS 2 kDa as a function of the laser energy against (c) the m/z value, (g) the
intensity, (k) the S/N ratio, (o) the resolution. Evaluation of the characteristic parameters of the MALDITOF MS spectra on the basis of the maximum peak for PEtOx 2 kDa as a function of the laser energy
against (d) the m/z value, (h) the intensity, (l) the S/N ratio, (p) the resolution.
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Figure S5: Representative spectra of PEG with the different matrices a) MHL, b) THP, c) RA, d) Chart
and e) AmB as well as f) a spectrum measured without matrix.
10
Figure S6: Representative spectra of PMMA with the different matrices a) MHL, b) THP, c) RA, d)
Chart and e) AmB as well as f) a spectrum measured without matrix.
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Figure S7: Representative spectra of PS with the different matrices a) MHL, b) THP, c) RA, d) Chart
and e) AmB as well as f) a spectrum measured without matrix.
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Figure S8: Representative spectra of PEtOx with the different matrices a) MHL, b) THP, c) RA, d)
Chart and e) AmB as well as f) a spectrum measured without matrix.
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Figure S9: a) Full MALDI-TOF MS spectrum of the PEG-PCL block copolymer measured with DCTB
and NaCl as matrix. b) Extended view of the region between m/z 2500 and 2550.
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