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S1
Electronic Supporting Information for:
Drug delivery and controlled release on biocompatible metal-
organic frameworks using mechanical amorphization
Claudia Orellana-Tavra,a Ross J. Marshall,
b Emma F. Baxter,
c Isabel Abanades Lazaro,
b Andi Tao,
a
Anthony K. Cheetham,c Ross S. Forgan
b,* and David Fairen-Jimenez
a,*
aAdsorption & Advanced Materials Laboratory (AAML), Department of Chemical Engineering &
Biotechnology, University of Cambridge, Pembroke Street, Cambridge CB2 3RA, UK. Email:
[email protected]; website: http://people.ds.cam.ac.uk/df334
bWestCHEM School of Chemistry, University of Glasgow, Joseph Black Building, University Avenue,
Glasgow, G12 8QQ, UK. Email: [email protected]; website: http://www.forganlab.com
cDepartment of Materials Science and Metallurgy, University of Cambridge, CB3 0FS Cambridge, UK
Contents
S1. Powder X-Ray Diffraction (PXRD) ........................................................................................................................................... 2
S2. Scanning electron microscopy (SEM) .................................................................................................................................... 3
S3. Nitrogen adsorption isotherms: experimental and simulated ..................................................................................... 3
S4. Pore size distribution analysis (PSD) ..................................................................................................................................... 4
S5. Stability analysis ............................................................................................................................................................................ 5
S6. XRD analysis after PBS exposure ............................................................................................................................................. 6
S7. FTIR .................................................................................................................................................................................................... 7
S8. Cytotoxicity analysis ..................................................................................................................................................................... 7
S9. Thermogravimetric analysis (TGA) ........................................................................................................................................ 9
S10. Delivery profiles from crystalline and amorphous Zr-based family ..................................................................... 10
S11. SEM nano-sized particles ...................................................................................................................................................... 12
S12. Cytotoxicity analysis of nano-sized particles ................................................................................................................. 13
S13. Cytotoxicity analysis of -CHC loaded nano-sized particles .................................................................................... 13
S14. Calibration curves of calcein and α-CHC in PBS ........................................................................................................... 14
Electronic Supplementary Material (ESI) for Journal of Materials Chemistry B.This journal is © The Royal Society of Chemistry 2016
S2
S1. Powder X-Ray Diffraction (PXRD)
Figure S1. Powder X-ray diffraction (PXRD) patterns of synthesized Zr-based MOFs compared with the calculated pattern for each. Colour code of patterns: black, calculated; blue, synthesized; red, loaded; and, yellow,
amorphisized. a) calcein loaded materials and, b) -CHC loaded materials.
2 10 18 26 34 42 50
Inte
ns
ity (
a.u
.)
2 q (º)
a)
5 15 25 35 45
Inte
ns
ity (
a.u
.)
2 q (º)
5 15 25 35 45
2 q (º)
2 10 18 26 34 42 50
2 q (º)
5 15 25 35 45
Inte
ns
ity (
a.u
.)
2 q (º)
Zr-L2
5 15 25 35 45
2 q (º)
5 15 25 35 45
2 q (º)
Zr-L3 Zr-L4
Zr-L7Zr-L6Zr-L5
Zr-L8
5 15 25 35 45
Inte
nsit
y (
a.u
.)
2 q (º)
5 15 25 35 45
2 q (º)
5 15 25 35 45
2 q (º)
5 15 25 35 45
Inte
ns
ity (
a.u
.)
2 q (º)
Zr-L1
5 15 25 35 45
2 q (º)
5 15 25 35 45
2 q (º)
b)
Zr-L2 Zr-L3
Zr-L6Zr-L5Zr-L4
S3
S2. Scanning electron microscopy (SEM)
Figure S2. SEM images for Zr-based MOFs, Zr-L1 to Zr-L8.
S3. Nitrogen adsorption isotherms: experimental and simulated
2 m
Zr-L1
5 m5 m 5 m
5 m 5 m5 m
5 m5 m
Zr-L2 Zr-L3 Zr-L4
Zr-L8Zr-L7Zr-L6Zr-L5
0
100
200
300
400
0 0.25 0.5 0.75 1
Ga
s u
pta
ke (
cm
3/g
)
P/P0
0
100
200
300
400
0 0.25 0.5 0.75 1
Ga
s u
pta
ke (
cm
3/g
)
P/P0
0
100
200
300
400
0 0.25 0.5 0.75 1
Ga
s u
pta
ke (
cm
3/g
)
P/P0
0
100
200
300
400
0 0.25 0.5 0.75 1
Ga
s u
pta
ke (
cm
3g
-1)
P/P0
0
200
400
600
800
1000
0 0.25 0.5 0.75 1
Ga
s u
pta
ke (
cm
3/g
)
P/P0
0
200
400
600
800
1000
0 0.25 0.5 0.75 1
Ga
s u
pta
ke (
cm
3g
-1)
P/P0
0
200
400
600
800
0 0.25 0.5 0.75 1
Ga
s u
pta
ke (
cm
3/g
)
P/P0
0
100
200
300
400
500
0 0.25 0.5 0.75 1
Gas u
pta
ke (
cm
3g
-1)
P/P0
Zr-L1 Zr-L2 Zr-L3 Zr-L4
Zr-L5 Zr-L6 Zr-L7 Zr-L8
a)
S4
Figure S3. N2 adsorption isotherms for Zr-based family, experimental (black closed dots) and simulated (red opened dots). a) linear scale; b) semi-log scale.
S4. Pore size distribution analysis (PSD)
Figure S4. PSD analysis for Zr-based family, experimental (black continued line) and simulated (red continued
line).
0
200
400
600
800
1000
1.E-09 1.E-07 1.E-05 1.E-03 1.E-01
Gas u
pta
ke (
cm
3/g
)
P/P0
0
200
400
600
800
1000
1.E-09 1.E-07 1.E-05 1.E-03 1.E-01
Gas u
pta
ke (
cm
3/g
)
P/P0
0
200
400
600
800
1.E-09 1.E-07 1.E-05 1.E-03 1.E-01
Gas u
pta
ke (
cm
3g
-1)
P/P0
0
100
200
300
400
500
1.E-09 1.E-07 1.E-05 1.E-03 1.E-01
Ga
s u
pta
ke (
cm
3g
-1)
P/P0
0
100
200
300
400
1.E-09 1.E-07 1.E-05 1.E-03 1.E-01
Gas u
pta
ke (
cm
3g
-1)
P/P0
0
100
200
300
400
1.E-09 1.E-07 1.E-05 1.E-03 1.E-01
Gas u
pta
ke (
cm
3g
-1)
P/P0
0
100
200
300
400
1.E-09 1.E-07 1.E-05 1.E-03 1.E-01
Gas u
pta
ke (
cm
3g
-1)
P/P0
0
100
200
300
400
1.E-09 1.E-07 1.E-05 1.E-03 1.E-01
Ga
s u
pta
ke (
cm
3g
-1)
P/P0
Zr-L1 Zr-L2 Zr-L3 Zr-L4
Zr-L5 Zr-L6 Zr-L7 Zr-L8
b)
0 5 10 15 20
PS
D (
a.u
.)
Pore diameter (Å)
0 5 10 15 20
PS
D (
a.u
.)
Pore diameter (Å)
Zr-L4
Zr-L8
0 5 10 15 20
PS
D (
a.u
.)
Pore diameter (Å)
0 5 10 15 20
PS
D (
a.u
.)
Pore diameter (Å)
Zr-L3
Zr-L7
0 5 10 15 20
PS
D (
a.u
.)
Pore diameter (Å)
0 5 10 15 20
PS
D (
a.u
.)
Pore diameter (Å)
Zr-L2
Zr-L6
0 5 10 15 20
PS
D (
a.u
.)
Pore diameter (Å)
0 5 10 15 20
PS
D (
a.u
.)
Pore diameter (Å)
Zr-L1
Zr-L5
S5
S5. Stability analysis
The kinetics of degradation from the solids were adjusted using non-linear regressions in order to understand their
behaviour. For Zr-L1 to Zr-L8 in PBS, and Zr-L2 to Zr-L7 in H2O the profile was adjusted to a simple hyperbola
model [1]:
N (wt. %)= 𝑁𝑚𝑎𝑥 t
(𝑡1/2 + t) [1]
where N is the amount of linker released from the solid, Nmax is the maximum amount released, t is time in days
and t1/2 is the time needed to get half of the maximum amount delivered.
For Zr-L1 in H2O it was not possible to adjust the delivery to a simple curve. Instead, we used a hyperbola model
considering two different release stages [2]:
N (wt. %)= 𝑁max(1) t
(𝑡1/2(1) + t)+ N2𝑡 + 𝑎 [2]
where Nmax and t1/2 are considered for the first stage of delivery and N2 and a are the slope and intercept of the
linear part of the release.
For Zr-L8 in H2O, we used a hyperbola model considering a slope factor or Hill slope, which is related with the
interactions material-solvent [3]:
N (wt. %)= 𝑁maxt^h
(𝑡1/2^h + t^h) [3]
where Nmax is the maximum amount released, t is time in days and t1/2 is the time needed to get half of the
maximum amount delivered and h is the Hill slope.
Figure S4 and Tables S1 show the fitting of the degradation in PBS and H2O of the materials.
Table S1: Fit-curves for degradation profiles of Zr-based MOFs.
PBS H2O
MOF Equation R2 Equation R
2
Zr-L1 linker (wt%) = 76.33 t / (0.004959 + t) 0.9943 linker (wt%) = 34.61 t / (0.04002 + t) + 1.111*t - 0.6783 0.9641
Zr-L2 linker (wt%) = 76.23 t / (0.003767 + t) 0.9962 linker (wt%) = 5.170 t / (4.693 + t) 0.9963
Zr-L3 linker (wt%) = 90.75 t / (0.003325 + t) 0.9945 linker (wt%) = 8.753 t / (3.610 + t) 0.9877
Zr-L4 linker (wt%) = 57.92 t / (0.01034 + t) 0.9936 linker (wt%) = 0.1868 t / (0.08060 + t) 0.9238
Zr-L5 linker (wt%) = 69.66 t / (0.04697 + t) 0.9640 linker (wt%) = 0.3950 t -0.01018 0.9943
Zr-L6 linker (wt%) = 100.4 t / (0.09548 + t) 0.9980 linker (wt%) = 3.603 t / (3.867 + t) 0.9949
Zr-L7 linker (wt%) = 95.06 t / (0.07875 + t) 0.9897 linker (wt%) = 98.08 t / (4.097 + t) 0.9887
Zr-L8 linker (wt%) = 90.59 t / (0.07071 + t) 0.9847 linker (wt%) = 14.77 t^7.286 / (1.621^7.286 + t^7.286) 0.9965
S6
Figure S5. Stability analysis of Zr-based MOFs in PBS (black closed dots) and H2O (red opened dots).
S6. XRD analysis after PBS exposure
Figure S6. PXRD analysis of Zr-based MOFs after PBS exposure for 2 days. Color code of patterns: black, calculated; blue, synthesized; red, degraded after 2 days in PBS.
0
20
40
60
80
100
0 1 2 3 4 5 6 7
Ma
ss
De
live
red
(%
)
Time (days)
0
20
40
60
80
100
0 1 2 3 4 5 6 7
Mass D
eli
vere
d (
%)
Time (days)
0
20
40
60
80
100
0 1 2 3 4 5 6 7
Ma
ss
De
live
red
(%
)
Time (days)
0
20
40
60
80
100
0 1 2 3 4 5 6 7
Ma
ss
De
live
red
(%
)
Time (days)
0
20
40
60
80
100
0 1 2 3 4 5 6 7
Mass D
eli
vere
d (
%)
Time (days)
0
20
40
60
80
100
0 1 2 3 4 5 6 7
Mass D
eli
vere
d (
%)
Time (days)
0
20
40
60
80
100
0 1 2 3 4 5 6 7
Mass D
eli
vere
d (
%)
Time (days)
0
20
40
60
80
100
0 1 2 3 4 5 6 7
Mass D
elivere
d (
%)
Time (days)
Zr-L1 Zr-L2 Zr-L3 Zr-L4
Zr-L5 Zr-L6 Zr-L7 Zr-L8
2 10 18 26 34 42 50
2 q (º)
2 10 18 26 34 42 50
2 q (º)
5 15 25 35 45
2 q (º)
5 15 25 35 45
Inte
ns
ity (
a.u
.)
2 q (º)
5 15 25 35 45
2 q (º)5 15 25 35 45
2 q (º)5 15 25 35 45
2 q (º)
5 15 25 35 45
Inte
ns
ity (
a.u
.)
2 q (º)
Zr-L1 Zr-L2 Zr-L3 Zr-L4
Zr-L8Zr-L7Zr-L6Zr-L5
S7
S7. FTIR
Figure S7. FTIR analysis of Zr-based MOFs after PBS exposure. Color code of patterns: black, no exposure to PBS; red, 2 days; and, blue, 3 days of PBS exposure.
S8. Cytotoxicity analysis
4000 3500 3000 2500 2000 1500 1000 500
Wavenumber (cm-1)
L4L4 degraded 2DL4 degraded 3D
4000 3500 3000 2500 2000 1500 1000 500
Wavenumber (cm-1)
L3L3 degraded 2DL3 degraded 3D
4000 3500 3000 2500 2000 1500 1000 500
Wavenumber (cm-1)
L2L2 degraded 2DL2 degraded 3D
4000 3500 3000 2500 2000 1500 1000 500
Tra
ns
mit
tan
ce
(%
)
Wavenumber (cm-1)
L1L1 degraded 2DL1 degraded 3D
4000 3500 3000 2500 2000 1500 1000 500
Wavenumber (cm-1)
L8L8 degraded 2DL8 degraded 3D
4000 3500 3000 2500 2000 1500 1000 500
Wavenumber (cm-1)
L7L7 degraded 2DL7 degraded 3D
4000 3500 3000 2500 2000 1500 1000 500
Wavenumber (cm-1)
L6L6 degraded 2DL6 degraded 3D
4000 3500 3000 2500 2000 1500 1000 500
Tra
ns
mit
tan
ce
(%
)
Wavenumber (cm-1)
L5L5 degraded 2DL5 degraded 3D
Zr-L1 Zr-L2 Zr-L3 Zr-L4
Zr-L5 Zr-L6 Zr-L7 Zr-L8
-
20
40
60
80
100
120
140
0.0 0.1 0.2 0.4 0.6 0.8 1.0
-
Concentration (mg/mL)
-
20
40
60
80
100
120
140
0.0 0.1 0.2 0.4 0.6 0.8 1.0
-
Concentration (mg/mL)
0
20
40
60
80
100
120
140
0 0.1 0.2 0.4 0.6 0.8 1
-
Concentration (mg/mL)
0
20
40
60
80
100
120
140
0.0 0.1 0.1 0.2 0.3 0.4 0.6 0.8 1.0
Via
bil
ity (
%)
Concentration (mg/mL)
-
20
40
60
80
100
120
140
0.0 0.1 0.2 0.4 0.6 0.8 1.0
-
Concentration (mg/mL)
-
20
40
60
80
100
120
140
0.0 0.1 0.2 0.4 0.6 0.8 1.0
-
Concentration (mg/mL)
-
20
40
60
80
100
120
140
0.0 0.1 0.2 0.4 0.6 0.8 1.0
-
Concentration (mg/mL)
-
20
40
60
80
100
120
140
0.00 0.10 0.20 0.40 0.60 0.80 1.00
Via
bil
ity (
%)
Concentration (mg/mL)
Zr-L1 Zr-L2 Zr-L3 Zr-L4
Zr-L5 Zr-L6 Zr-L7 Zr-L8
a)
S8
Figure S8. Cytotoxicity analysis. a) MTS assay for Zr-based MOFs; b) MTS assay for zirconium tetrachloride and
each organic linker of the Zr-based family. L8 was not measured as Zr-L8 showed cytotoxicity.
-
20
40
60
80
100
120
140
0.0 0.1 0.2 0.4 0.6 0.8 1.0
Via
bil
ity (
%)
Concentration (mg/mL)
-
20
40
60
80
100
120
140
0.0 0.1 0.2 0.4 0.6 0.8 1.0
-
Concentration (mg/mL)
-
20
40
60
80
100
120
140
0.0 0.1 0.2 0.4 0.6 0.8 1.0
-
Concentration (mg/mL)
-
20
40
60
80
100
120
140
0.0 0.1 0.2 0.4 0.6 0.8 1.0
Via
bilit
y (
%)
Concentration (mg/mL)
-
20
40
60
80
100
120
140
0.0 0.1 0.2 0.4 0.6 0.8 1.0
-
Concentration (mg/mL)
-
20
40
60
80
100
120
140
0.0 0.1 0.2 0.4 0.6 0.8 1.0
-
Concentration (mg/mL)
-
20
40
60
80
100
120
140
0.0 0.1 0.2 0.4 0.6 0.8 1.0
-
Concentration (mg/mL)
-
20
40
60
80
100
120
140
0.0 0.1 0.2 0.4 0.6 0.8 1.0
Via
bilit
y (
%)
Concentration (mg/mL)
ZrCl4 L1 L2 L3
L4 L5 L6 L7
b)
0
2
4
6
8
0.25 0.50 1.00
Via
bil
ity (
%)
Concentration (mg/mL)
0
2
4
6
8
0.25 0.50 1.00
LD
H r
ele
as
ed
(%
)
Concentration (mg/mL)
0
2
4
6
8
0.25 0.50 1.00
Via
bil
ity (
%)
Concentration (mg/mL)
0
2
4
6
8
0.25 0.50 1.00
Via
bil
ity (
%)
Concentration (mg/mL)
0
2
4
6
8
0.25 0.50 1.00
Via
bil
ity (
%)
Concentration (mg/mL)
0
2
4
6
8
0.25 0.50 1.00
LD
H r
ele
as
ed
(%
)
Concentration (mg/mL)
Zr-L1 Zr-L2 Zr-L3 Zr-L4
Zr-L6
a)
Zr-L5
S9
Figure S9. Cytotoxicity analysis. a) LDH assay for Zr-based MOFs and b) LDH assay for zirconium tetrachloride and each organic linker of the Zr-based MOF family.
S9. Thermogravimetric analysis (TGA)
0
2
4
6
8
0.25 0.50 1.00
Via
bilit
y (
%)
Concentration (mg/mL)
0
2
4
6
8
0.25 0.50 1.00
Via
bilit
y (
%)
Concentration (mg/mL)
0
2
4
6
8
0.25 0.50 1.00
LD
H r
ele
as
ed
(%
)
Concentration (mg/mL)
0
2
4
6
8
0.25 0.50 1.00
Via
bilit
y (
%)
Concentration (mg/mL)
0
2
4
6
8
0.25 0.50 1.00
Via
bil
ity (
%)
Concentration (mg/mL)
0
2
4
6
8
0.25 0.50 1.00
Via
bil
ity (
%)
Concentration (mg/mL)
0
2
4
6
8
0.25 0.50 1.00
LD
H r
ele
as
ed
(%
)
Concentration (mg/mL)
b)ZrCl4 L1 L2 L3
L4 L5 L6
30
40
50
60
70
80
90
100
0 100 200 300 400 500 600
We
igh
t (%
)
Temperature ( C)
30
40
50
60
70
80
90
100
0 100 200 300 400 500 600
We
igh
t (%
)
Temperature ( C)
30
40
50
60
70
80
90
100
0 100 200 300 400 500 600
We
igh
t (%
)
Temperature ( C)
30
40
50
60
70
80
90
100
0 100 200 300 400 500 600
Weig
ht
(%)
Temperature ( C)
Zr-L2
30
40
50
60
70
80
90
100
0 100 200 300 400 500 600
Weig
ht
(%)
Temperature ( C)
Zr-L3 Zr-L4
Zr-L5 Zr-L6
a)
S10
Figure S10. Thermogravimetric analysis (TGA) of synthesized Zr-based MOFs compared with the loaded material.
a) calcein loaded materials and, b) -CHC loaded materials. Color code of patterns: black, empty material; red, loaded material; blue, free drug.
S10. Delivery profiles from crystalline and amorphous Zr-based family
The kinetics of calcein and -CHC delivery from crystalline and amorphous solids were adjusted using non-linear
regressions in order to understand the release behaviour. For the calcein loaded Zr-L3 to Zr-L6, amZr-L3 and amZr-
L6 materials the delivery was adjusted to a simple hyperbola model [4]:
N (wt. %)= 𝑁𝑚𝑎𝑥 t
(𝑡1/2 + t) [4]
where N is the amount released from the total drug-loaded amount in weight percent, Nmax is the maximum
amount released, t is time in days and t1/2 is the time needed to get half of the maximum amount delivered.
For the calcein loaded Zr-L2, amZr-L2, amZr-L4, amZr-L5 and all the -CHC loaded materials (crystalline and
amorphous) it was not possible to adjust the delivery to a simple curve. Instead, we used a hyperbola model
considering two different release stages [5]:
N (wt. %)= 𝑁max(1) t
(𝑡1/2(1) + t)+ N2𝑡 + 𝑎 [5]
where Nmax and t1/2 are considered for the first stage of delivery and N2 and a are the slope and intercept of the
linear part of the release.
Figure S8 and Tables S2 and S3 show the fitting of the experimental release and fitting parameters, respectively,
for calcein loaded and -CHC loaded materials. In both cases, as it was possible to detect the calcein and -CHC
delivered form all the amorphous materials it is possible to conclude that the ball-milling process is not provoking
the release of guest molecules.
30
40
50
60
70
80
90
100
0 100 200 300 400 500 600
Weig
ht
(%)
Temperature ( C)
30
40
50
60
70
80
90
100
0 100 200 300 400 500 600
Weig
ht
(%)
Temperature ( C)
30
40
50
60
70
80
90
100
0 100 200 300 400 500 600
Weig
ht
(%)
Temperature ( C)
30
40
50
60
70
80
90
100
0 100 200 300 400 500 600
Weig
ht
(%)
Temperature ( C)
30
40
50
60
70
80
90
100
0 100 200 300 400 500 600
Weig
ht
(%)
Temperature ( C)
30
40
50
60
70
80
90
100
0 100 200 300 400 500 600
Weig
ht
(%)
Temperature ( C)
b)
Zr-L1 Zr-L2 Zr-L3
Zr-L4 Zr-L5 Zr-L6
S11
Figure S11. Release profile of a) calcein and b) -CHC from the crystalline (in black closed dots) and amorphous (in red opened dots) materials. Black solid and red dotted lines represent the kinetic of delivery fitting using non-linear regression on crystalline and amorphous materials, respectively.
0
20
40
60
80
100
0 5 10 15
Ma
ss
De
live
red
(%
)
Time (days)
0
20
40
60
80
100
0 2 4 6
Ma
ss
De
live
red
(%
)
Time (days)
0
20
40
60
80
100
0 5 10 15
Mass D
eli
vere
d (
%)
Time (days)
0
20
40
60
80
100
0 2 4 6
Mass D
elivere
d (
%)
Time (days)
0
20
40
60
80
100
0 1 2 3 4
Mass D
eli
vere
d (
%)
Time (days)
Zr-L2 Zr-L3 Zr-L4
Zr-L5 Zr-L6
a)
0
20
40
60
80
100
0 1 2 3
Ma
ss
De
live
red
(%
)
Time (days)
0
20
40
60
80
100
0 1 2 3
Mass D
eli
vere
d (
%)
Time (days)
0
20
40
60
80
100
0 1 2 3
Mass D
eli
vere
d (
%)
Time (days)
0
20
40
60
80
100
0 1 2 3
Ma
ss D
eli
ve
red
(%
)
Time (days)
0
20
40
60
80
100
0 1 2 3
Ma
ss
De
live
red
(%
)
Time (days)
b)
Zr-L1 Zr-L2 Zr-L3
Zr-L4 Zr-L5 Zr-L60
20
40
60
80
100
0 1 2 3
Mass D
elivere
d (
%)
Time (days)
S12
Table S2: Fit-curves for calcein release from crystalline and amorphous Zr-based solids.
Crystalline Amorphous
MOF Equation R2 Equation R
2
Zr-L2 cal (wt%) = 82.21 t / (0.08366 + t) - 0.3220*t + 13.14 0.9900 cal (wt%) = 58.09 t / (0.4098 + t) – 0.2811*t + 10.47 0.9879
Zr-L3 cal (wt%) = 96.73 t / (0.07250 + t) 0.9902 cal (wt%) = 76.26 t / (1.007 + t) 0.9858
Zr-L4 cal (wt%) = 95.21 t / (0.04873 + t) 0.9540 cal (wt%) = 84.62 t / (0.9402 + t) + 0.8159*t - 2.879 0.9958
Zr-L5 cal (wt%) = 99.42 t / (0.2481 + t) 0.9964 cal (wt%) = 126.3 t / (0.5592 + t) - 2.3040*t - 8.367 0.9824
Zr-L6 cal (wt%) = 100.7 t / (0.05676 + t) 0.9912 cal (wt%) = 99.27 t / (0.2279 + t) 0.9864
Table S3: Fit-curves for -CHC release from crystalline and amorphous Zr-based solids.
Crystalline Amorphous
MOF Equation R2 Equation R
2
Zr-L1 α-CHC (wt%) = 89.79 t / (0.02686 + t) - 1.111*t + 13.99 0.9973 α-CHC (wt%) =94.42 t / (0.02567 + t) – 1.595*t + 10.41 0.9738
Zr-L2 α-CHC (wt%) = 78.86 t / (0.06801 + t) - 1.226*t + 23.84 0.9836 α-CHC (wt%) = 62.84 t / (0.02967 + t) + 2.931*t + 29.91 0.9961
Zr-L3 α-CHC (wt%) = 77.37 t / (0.06562 + t) - 1.446*t + 18.99 0.9700 α-CHC (wt%) = 69.61 t / (0.06692 + t) - 1.948*t + 17.47 0.9776
Zr-L4 α-CHC (wt%) = 93.47 t / (0.07793 + t) – 1.420*t + 10.68 0.9753 α-CHC (wt%) = 89.24 t / (0.04578 + t) – 1.254*t + 15.70 0.9858
Zr-L5 α-CHC (wt%) = 96.202 t / (0.04517 + t) - 0.8328*t + 6.8 0.9964 α-CHC (wt%) = 85.93 t / (0.03250 + t) - 0.9927*t + 8.976 0.9974
Zr-L6 α-CHC (wt%) = 45.48 t / (0.08153 + t) + 1.833*t + 48.48 0.9832 α-CHC (wt%) = 57.66 t / (0.02727 + t) + 3.330*t + 30.01 0.9974
S11. SEM nano-sized particles
Figure S12. SEM images of nano-sized Zr-based MOFs.
2 m
Zr-L1
5 m
Zr-L2
1 m
Zr-L3
1 m
1 m
Zr-L4 Zr-L6
5 m
Zr-L5
1 m
S13
S12. Cytotoxicity analysis of nano-sized particles
Figure S13. MTS assay of nano-sized Zr-based MOFs.
S13. Cytotoxicity analysis of -CHC loaded nano-sized particles
Table S4: Loading values for α-CHC into Zr-based nano-sized materials. The values were measured using UV-vis. Loading value of Zr-L1 is the same presented before as this was the same exactly material.
MOF α-CHC (wt.%)
Zr-L1 31
Zr-L2 1
Zr-L3 2
Zr-L4 4
Zr-L5 12
Zr-L6 20
-
20
40
60
80
100
120
140
0 0.25 0.5 1
Via
bilit
y (
%)
Concentration (mg/mL)
-
20
40
60
80
100
120
140
0 0.25 0.5 1
Via
bilit
y (
%)
Concentration (mg/mL)
-
20
40
60
80
100
120
140
0 0.25 0.5 1
Via
bilit
y (
%)
Concentration (mg/mL)
-
20
40
60
80
100
120
140
0 0.25 0.5 1
Via
bilit
y (
%)
Concentration (mg/mL)
-
20
40
60
80
100
120
140
0 0.25 0.5 1
Via
bilit
y (
%)
Zr-L5 concentration (mg/mL)
Zr-L1 Zr-L2 Zr-L3
Zr-L5 Zr-L6
S14
Figure S14. MTS assay of -CHC loaded nano-sized Zr-based MOFs and free -CHC. * indicates P ≤ 0.05 in comparison with the empty Zr-L6 MOF (Student’s test). Black bars correspond to empty material and white ones to loaded MOF.
S14. Calibration curves of calcein and α-CHC in PBS
Figure S15. Calibration curve in PBS pH 7.4 for calcein (left) and α-CHC (right) used for the release experiments.
0
20
40
60
80
100
120
140
0 0.05 0.1 0.25 1V
iab
ilit
y (
%)
Concentration (mg/mL)
-
20
40
60
80
100
120
140
Via
bilit
y (
%)
Concentration (mg/mL)
-CHC (mg/mL)
0.25 0.5 1
-
20
40
60
80
100
120
140
Via
bilit
y (
%)
Concentration (mg/mL)
-CHC(mg/mL)
0.25 0.5 1
-
20
40
60
80
100
120
140
Via
bilit
y (
%)
Concentration (mg/mL)
-CHC (mg/mL)
0.25 0.5 1
0
20
40
60
80
100
120
140V
iab
ilit
y (
%)
Concentration (mg/mL)
-CHC (mg/mL)
0.25 0.5 1
-
20
40
60
80
100
120
140
Via
bilit
y (
%)
Concentration (mg/mL)
-CHC (mg/mL)
0.25 0.5 1
-
20
40
60
80
100
120
140
Via
bil
ity (
%)
Concentration (mg/mL)
-CHC(mg/mL)
0.25 0.5 1
Zr-L1 Zr-L2 Zr-L3 Zr-L4
Zr-L5 Zr-L6 α-CHC*
y = 95.305x - 0.399R² = 0.9989
0
20
40
60
80
100
120
140
0.0 0.5 1.0 1.5
Ca
lce
in c
on
ce
ntr
ati
on
[µ
g/m
L]
Abs 498 nm
y = 39.622x + 0.6357R² = 0.9996
0
10
20
30
40
50
60
70
80
90
0.0 0.5 1.0 1.5 2.0 2.5
α-C
HC
Co
nc
en
tra
tio
n [
µg
/mL
]
Abs 337 nm
