Synthesis, crystal structures, DFT studies, antibacterial ... · Carlos Tenorio Clavijoa, Douglas Henrique Pereirab, Wilton Rogério Lustric and Pedro Paulo Corbia*. a Institute of

Supplementary material Pereira et al.

1

Synthesis, crystal structures, DFT studies, antibacterial assays and interaction

assessments with biomolecules of new platinum(II) complexes with

adamantane derivatives

Anna Karla dos Santos Pereiraa*, Carlos Marrote Manzanoa, Douglas Hideki Nakahataa Juan

Carlos Tenorio Clavijoa, Douglas Henrique Pereirab, Wilton Rogério Lustric and Pedro Paulo

Corbia*.

a Institute of Chemistry, University of Campinas – UNICAMP, PO Box 6154, 13083-970 Campinas, SP,

Brazil.

b Chemistry Collegiate, Federal University of Tocantins, Campus Gurupi, PO Box 66, Gurupi 77 402-970,

Brazil.

c Department of Biological and Health Sciences, University of Araraquara, UNIARA, 14801-320, São

Paulo, Brazil.

*Corresponding authors

E-mail:[email protected] / [email protected]

Contents

Infrared Spectra······························································································ 2

Thermogravimetric curves·············································································· 4

Crystallography······························································································ 7

Molecular modeling······················································································ 10

Mass spectra··································································································· 11

1H NMR assignments and chemical shifts (ppm) ··········································· 12

{15N, 1H} NMR 2D contour maps··································································· 13

1H NMR kinetics study···················································································· 14

Interaction with DNA······················································································ 15

Interaction with BSA······················································································ 17

Electronic Supplementary Material (ESI) for New Journal of Chemistry.This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2020


2

Infrared spectra

The infrared spectra of the complexes Pt-atd, Pt-rtd and Pt-mtn and their precursors

are shown in Figure S1. The bands in the region of 2903-2841 cm-1 can be attributed to the

ν(CH) and ν(CH2) stretches of the adamantane cage1 of the ligands. Bands in the region

3273-3104 cm-1 in the spectra of the complexes correspond to the asymmetric and

symmetric (NH2) stretching modes of the coordinated amino group2. These same bands are

not evident in the spectra of the ligands because in this case they are in the hydrochloride

form and, therefore, the stretching modes of the amino group ν(NH3+) are overlapped. The

bands in the region between 1582-1565 cm-1 were attributed to δ(H-N-H) vibrations3.

Strong bands of absorption in the region 1131-1110 cm-1 and 1034-1017 cm-1 were

attributed to the νS=O and νC-S vibrations, respectively, which confirms sulfur

coordination of DMSO molecule to the Pt(II) center4. Finally, the bands in the region 445-

438 cm-1 can be attributed to the νPt-S vibration mode characteristic of platinum complexes

with S-coordinated sulfoxides.5


3

Figure S1. Infrared spectra of the (a) platinum(II) complexes and (b) precursors.

4000 3500 3000 2500 2000 1500 1000 500

Pt-rtd

Pt-mtn

Wavenumber (cm-1)

Pt-atd

2903

2847

1574

(N-H)

2903

3225

1565

(N-H)

1582

(N-H)

2903

3186

2847

3190

3109

3273

2841

3115

1131

(S=O)

1123

(S=O)

1110

(S=O) 1034

(C-S)

1017

(C-S)

1024

(C-S)

438

Pt-S

438

Pt-S

445

Pt-S

(a)

4000 3500 3000 2500 2000 1500 1000 500

rtdH

cis - [PtCl2(DMSO)

2]

Wavenumber (cm-1)

mtnH

atdH

(b)


4

Thermogravimetric analysis

The thermogravimetric curves for the platinum complexes are shown in Figure S2.

According to the experimental data, the Pt-atd compound starts to decompose at 160 °C

with mass loss of 56.4% until 400 °C. The mass loss can be attributed to organic fraction

of the molecule (calcd. 57.4%). The final residue corresponding to 42.6% is consistent with

the formation of platinum oxide, PtO (calcd. 43.6%). For Pt-rtd compound, the thermal

decomposition starts at 160 ºC with a mass loss of 44.10% from 160 - 257 °C, which is

equivalent to the loss of rtd and DMSO molecules (calcd. 46.5%). There is a subsequent

weight loss of 14.1% from 257 - 360 °C, which is consistent with the loss of two Cl atoms

(calcd. 13.6%) with the formation of a final residue of 41.4%, which is consistent with

platinum oxide, PtO (calcd. 40.3%). For Pt-mtn, there is a first step of mass loss of 2% from

25 to 120 °C, which was attributed to the loss of water or residual solvent. From 120 °C to

696 °C a mass loss of 54.8% was observed, which corresponds to the loss of one mtn and

DMSO molecule and two Cl atoms (calcd. 59.7%). In 696 °C there is a residue of 41.4%

which is consistent with the formation of PtO (calcd. 40.3%). From 696 °C to 900 °C there

is a mass loss which, probably, corresponds to the reduction of PtO to Pt°. The thermal

decomposition data are summarized in Table S1. The experimental thermogravimetric data

reinforces the composition of the complexes as verified by elemental analyses and

crystallographic data.


5

Figure S2. The TGA and DTG curves of (a) Pt-atd, (b) Pt-rtd and (c) Pt-mtn.

0 200 400 600 800 1000

0

50

100

150

200

250

300

Temperature, ºC

DT

G,

g m

in-1

422 ºC

789 ºC

43 ºC

20

40

60

80

100

DTG

Mass, %

TG

0 200 400 600 800 1000

0.0

0.2

0.4

0.6

0.8

1.0

Temperature, ºC

DT

G, m

g m

in-1

344ºCTG

DTG 40

60

80

100

Mass, %

0 200 400 600 800 1000-0.2

0.0

0.2

0.4

0.6

0.8

1.0

1.2

Temperature, ºC

DT

G, m

g m

in -1

246ºC

315ºC

TG

DTG40

60

80

100M

ass, %(b) Pt-rtd(a) Pt-atd

(c) Pt-mtn

Temperature (ºC) Temperature (ºC)

Temperature (ºC)


6

Table S1: Thermal behavior data of the complexes.

Complex steps Temperature

range (ºC)

DTG

peak

TG weight loss, % Assignment

Calcd. Found

Pt-atd

Residue

1st

160 – 400

344 ºC

57.4

42.6

56.4

43.6

Ligand +

(CH3)2SO + 2Cl

PtO

Pt-rtd

Residue

1st

2nd

160 – 257

257 – 360

246 ºC

315 ºC

46.1

13.6

40.3

44.5

14.1

41.4

Ligand +

(CH3)2SO + 2Cl

PtO

Pt-mtn

Residue

1st

2nd

3rd

26 – 120

120 – 696

696 – 900

43 ºC

422 ºC

789 ºC

59.7

40.3

2.00

54.8

43.2

Residual solvent

Ligand +

(CH3)2SO + 2Cl

PtO

Pt°


7

Crystallography

Table S2: Experimental details for crystal structure determination and refinement of Pt-atd, Pt-rtd

and Pt-mtn.

Parameter Pt-atd Pt-rtd Pt-mtn

Chemical formula C12H23Cl2NOPtS C14H27Cl2NOPtS C14H27Cl2NOPtS

Molecular weight (g·mol-1) 495.37 523.42 523.42

Crystal system, space group Monoclinic, P21/c Monoclinic, P21/c Orthorhombic, Pbca

Temperature (K) 150 150 150

a, b, c (Å) 12.7546 (18), 32.285

(5), 15.611(2)

13.405 (2), 9.4994

(14), 14.267(2)

19.6534 (16), 8.5150

(7), 21.5493 (17)

β (°) 90.421 (3) 102.871 (3) 90

V (Å3) 6428.16 1771.1 3606.2 (5)

Z 16 4 8

Radiation type Mo Kα Mo Kα Mo Kα

µ (mm−1) 9.183 8.338 8.190

Crystal size (mm) 0.12 x 0.11 x 0.07 0.18 x 0.08 x 0.07 0.33 × 0.25 × 0.13

Tmin, Tmax 0.615, 0.745 0.561, 0.746 0.551, 0.746

No. of measured, independent and

observed [I > 2σ(I)] reflections

121659, 13309, 10507 24304, 4378, 3547 84848, 5512, 5117

Rint 0.067 0.046 0.025

(sin θ/λ)max (Å−1) 0.628 0.666 0.715

R[F2 > 2σ(F2)], wR(F2), S 0.038, 0.065, 1.11 0.026, 0.058, 1.02 0.020, 0.039, 1.23

No. of reflections 13309 4378 5512

No. of parameters 597 184 193

Δρmax, Δρmin (e Å−3) 1.22, -1.51 2.45, -1.04 1.22, −1.68


8

Figure S3. Crystal packing of (a) Pt-atd, (b) Pt-rtd and (c) Pt-mtn. *The four symmetrically

independent Pt-atd molecules are color-coded: green - Pt1A, red - Pt1B, yellow - Pt1C, blue -

Pt1D.

(a)

(b)

(c)


9

Figure S4. Intermolecular interactions in (a) Pt-atd, (b) Pt-rtd and (c) Pt-mtn. Symmetry codes: (i):

-x, 1/2 + y, 1/2 – z; (ii): 1 – x, -1/2 + y, 1/2 – z; (iii): 3/2 – x, -1/2 + y, z; (iv): 1 – x, 1 – y, 1 – z.

N1APt1B

Pt1

Cl2

C4i

C13ii

O1ii

(a)

(b)

(c)

Cl1

Pt1A

O1A

Cl2A

O1B

Cl1A

N1B

Cl2B

C13iii

O1iii

N1

C10

Cl2iv

C14

Cl2

C14iv

C10iv


10

Molecular modeling

Figure S5. HOMO, LUMO and gap for: A1) atd, A2) cis-[PtCl2(atd)(Me2SO)], A3) trans-[PtCl2(atd)(Me2SO)], M1) mtn, M2) cis-

[PtCl2(mtn)(Me2SO)], M3) trans-[PtCl2(mtn)(Me2SO)], R1) rtd, R2) cis-[PtCl2(rtd)(Me2SO)], R3) trans-[PtCl2(rtd)(Me2SO)]. Data

obtained at the theory level B3LYP/6-31+G(d,p)/LANL2DZ. Me2SO is dimethylsulfoxide.


11

Mass spectra

Figure S6. Mass spectra of (a) Pt-atd, (b) Pt-rtd and (c) Pt-mtn.

m/z100 200 300 400 500 600 700 800 900 1000 1100 1200 1300 1400

%

0

100

m/z100 200 300 400 500 600 700 800 900 1000 1100 1200 1300 1400

%

0

100

m/z100 200 300 400 500 600 700 800 900 1000 1100 1200 1300 1400

%

0

100

15-08-18_ATD-PT 23 (0.410) Cm (1:57) TOF MS ES+ 1.97e4311.0739249.1341

221.1074 250.1448312.0802496.0482460.0752

05-09-18_PT-RTD 55 (0.956) Cm (1:57) TOF MS ES+ 2.25e3566.1272

565.1329

564.1245

179.0234258.1948

194.9922

541.1207

505.1255398.5309259.1932

568.1333

602.1131

605.1165

05-09-18_PT-MTN 50 (0.871) Cm (1:57) TOF MS ES+ 2.35e31047.1417

1046.1583

1045.1545

524.0769

523.0914

520.1259

1044.1514526.0799

541.1060 1043.1489703.2385

562.0353 1008.1580706.2314

1048.1464

1050.1365

1051.1426

1226.32421067.1593

1087.0950 1229.32061232.2982

[Pt(rtd)(DMSO)2Cl2 + H]+

[Pt(mtn)(DMSO)Cl2 + H]+

[Pt(atd)(DMSO)Cl2 + H]+

2[Pt(mtn)(DMSO)Cl2 + H]+

[Pt(atd)(DMSO)Cl]+

[Pt(rtd)(DMSO)2Cl]+

[Pt(mtn)2 (DMSO)Cl2 + H]+

2[Pt(mtn)2(DMSO)Cl2 + H]+

(a)

(b)

(c)


12

1H NMR assignments and chemical shifts (ppm)

Figure S7. 1H NMR spectra of (a) atdH, (b) rtdH and (c) mtnH in DMSO-d6 and of (d) Pt-atd, (e) Pt-rtd and (f) Pt-mtn in CD2Cl2

(d)

(e)

(f)

DM

SO

DM

SO

DM

SO

CD

2C

l 2C

D2C

l 2C

D2C

l 2

NH

2

NH2

NH

2

-CH

3

H8 H10

H2,

6

H7,

9

H4

H3,

5,

8

H2,

6,

10

H4,

7,

9

-CH

3

H1

H4,

9,

6

H3,

7,

11H

5,

8,

10

H3,

5,

8

H2,

6,

10

H4,

7,

9

DM

SO

H2O

NH

3

-CH

3

H10H

2,

6

H4

H7,

9

H8

DM

SO

H2O

NH

3

NH

3

-CH

3

H1

H4,

9,

6

H5,

8,

10

H3,

7,

11

DM

SO

H2O

(a)

(b)

(c)


13

{15N, 1H} NMR 2D contour maps

Figure S8. {15N, 1H} HMBC contour maps of (a) atdH, (b) rtdH, (c) mtnH in DMSO-d6 and of (d)

Pt-atd, (e) Pt-rtd and (f) Pt-mtn in CD2Cl2.

δ 15N 60.6 ppmδ 15

N 42.6 ppmδ 15N 62.0 ppm

δ 15N 36.2 ppm δ 15

N 10.0 ppm δ 15N 34.8 ppm

(a) atdH

(d) Pt-atd

(b) rtdH

(e) Pt-rtd (f) Pt-mtn

(c) mtnH


14

1H NMR kinetics studies

Figure S9: Kinetic studies of (a) Pt-atd, (b) Pt-rtd and (c) Pt-mtn for 24 hours, followed by 1H

NMR. Signals of coordinated DMSO (close to 3.3 ppm) and uncoordinated DMSO (2.55 ppm) are

indicated by the arrows. For Pt-rtd and Pt-mtn the intensity of the signals between 1.00 and 1.80

ppm were increased for improved visualization.

(a)

(b)

(c)


15

Interaction with DNA

Figure S10: Agarose gel electrophoresis for the pGEX-4T1 plasmid DNA in the presence of the

compounds at concentrations of 80 µmol·L-1. OC = Open circular, LF = linear form and SC=

supercoiled forms of the plasmid.

Lad

der

pG

EX

-4T

1

atd

H

rtd

H

mtn

H

Pt-

atd

Pt-

rtd

Pt-

mtn

K2[P

dC

l 4]

[PtC

l 2(D

MS

O) 2

]

Cis

pla

tin

Lad

der

pG

EX

-4T

1

[PtC

l 2(D

MS

O) 2

]

atd

H

Lad

der

pG

EX

-4T

1

[PtC

l 2(D

MS

O) 2

]

rtd

H

atd

H

Lad

der

pG

EX

-4T

1

[PtC

l 2(D

MS

O) 2

]

mtn

H

rtd

H

atd

H

Lad

der

pG

EX

-4T

1

[PtC

l 2(D

MS

O) 2

]

Pt-

atd

mtn

H

rtd

H

atd

H

Lad

der

pG

EX

-4T

1

[PtC

l 2(D

MS

O) 2

]

Pt-

rtd

Pt-

atd

mtn

H

rtd

H

atd

H

Lad

der

pG

EX

-4T

1

[PtC

l 2(D

MS

O) 2

]

Pt-

mtn

Pt-

rtd

Pt-

atd

mtn

H

rtd

H

atd

H

Lad

der

pG

EX

-4T

1

[PtC

l 2(D

MS

O) 2

]

OC

LF

SC


16

Figure S11. Circular dichroism spectra of CT-DNA (100 μM) in the absence and presence of (a)

amantadine hydrochloride (b) rimantadine hydrochloride and (c) memantine hydrochloride at r =

0.1, 0.3 and 0.5.

(a) (b)

(c)


17

Interaction with BSA

Figure S12: Fluorescence spectra of BSA in the absence and presence of the (a) Pt-atd, (b) Pt-rtd,

(c) Pt-mtn and (d) [PtCl2(DMSO)2] complexes. [BSA] = 2.4 × 10−6 µmol·L-1. [Complexes] = 0.0,

5.0, 10.0, 15.0, 20.0, 25.0, 30.0, 35.0, 40.0, 45.0 and 50.0 µmol·L-1.

300 320 340 360 380 400 420 440 4600

200

400

600

800

1000

0.00 1.50x10-5

3.00x10-5

4.50x10-5

6.00x10-5

0.75

1.00

1.25

1.50

Fo/F

[Q]Inte

nsi

ty (

a.u

.)

Wavelength (nm)

300 320 340 360 380 400 420 440 4600

200

400

600

800

1000

0.00 1.50x10-5

3.00x10-5

4.50x10-5

6.00x10-5

0.75

1.00

1.25

1.50

1.75

2.00

2.25

2.50

Fo

/F

[Q]

Inte

nsi

ty (

a.u

.)

Wavelength (nm)

300 320 340 360 380 400 420 440 4600

200

400

600

800

1000

0.00 1.50x10-5

3.00x10-5

4.50x10-5

6.00x10-5

0.75

1.00

1.25

1.50

Fo

/F

[Q]

Inte

nsi

ty (

a.u

.)

Wavelength (nm)

(a)Pt-atd (b)Pt-rtd

(c)Pt-mtn

300 320 340 360 380 400 420 440 4600

200

400

600

800

1000

0.00 1.50x10-5

3.00x10-5

4.50x10-5

6.00x10-5

0.75

1.00

1.25

1.50

Fo

/F

[Q]

Inte

nsi

ty (

a.u

.)

Wavelength (nm)

(d)[PtCl2(DMSO)2]


18

Figure S13. Plots for the interaction of (a) Pt-atd, (b) Pt-rtd, (c) Pt-mtn and (d) [PtCl2(DMSO)2]

complexes with fluorescence maxima of BSA at 347 nm.

-5.50 -5.25 -5.00 -4.75 -4.50 -4.25 -4.00-2.5

-2.0

-1.5

-1.0

-0.5

0.0

0.5

log

(F

o-F

)/F

log [Q]

y = 3.408 + 0.889x

(a) Pt-atd

(c) Pt-mtn

-5.50 -5.25 -5.00 -4.75 -4.50 -4.25 -4.00-2.5

-2.0

-1.5

-1.0

-0.5

0.0

0.5

log

(F

o-F

)/F

log [Q]

y = 4.865 + 1.133x

(b) Pt-rtd

-5.50 -5.25 -5.00 -4.75 -4.50 -4.25 -4.00-2.5

-2.0

-1.5

-1.0

-0.5

0.0

0.5

log

(F

o-F

)/F

log [Q]

y = 3.937 + 1.096x

-5.50 -5.25 -5.00 -4.75 -4.50 -4.25 -4.00-2.5

-2.0

-1.5

-1.0

-0.5

0.0

0.5

log

(F

o-F

)/F

log [Q]

y = 3.092 + 0.855x

(d) [PtCl2(DMSO)2]


19

References

1 J. C. Garcia, J. F. Justo, W. V. M. Machado and L. V. C. Assali, J. Phys. Chem. A, 2010,

114, 11977–11983.

2 S. Podunavac-Kuzmanovic, D. Cvetkovic and L. Vojinovic, Acta Period. Technol., 2004,

35, 239–246.

3 D. Jeremic, M. Djordjevic, S. Miletic, L. Andjelkovic, D. Sladic and I. Brceski, J. Serbian

Chem. Soc., 2018, 83, 699–705.

4 P. Van Thong, D. T. Thom, N. Thi and T. Chi, 2018, 56, 146–151.

5 V. Y. Kukushkin, V. K. Belsky, V. E. Konovalov, G. A. Kirakosyan, L. V. Konovalov, A.

I. Moiseev and V. M. Tkacbuk, Inorganica Chim. Acta, 1991, 185, 143–154.

Documents

Synthesis, crystal structures, DFT studies, antibacterial ... · Carlos Tenorio Clavijoa, Douglas Henrique Pereirab, Wilton Rogério Lustric and Pedro Paulo Corbia*. a Institute of