NMR CRYSTALLOGRAPHY: NMR CRYSTALLOGRAPHY: The new application of combined theoretical The new application of combined theoretical
and spectroscopic approach for structural and spectroscopic approach for structural description in the solid statedescription in the solid state
Anife Ahmedova, Miroslava Nedyalkova, Mariana MitewaUniversity of Sofia
Vladislav AntonovInstitute for Nuclear Research and Nuclear Energy
NMR NMR CRYSTALLOGRAPHYCRYSTALLOGRAPHY
NMR experimentsin the solid state
Single-crystal or powder diffraction
CALCULATIONS
To define a space group, conformational changesor even structural parameters
Application to structural biology, organic and pharmaceutical chemistry,
inorganic and materials chemistry
Commonly studiedrelation
Structural data
Spectroscopic and/or biological experiments
Theoretical calculations
Frequently ignoreddetails !!!
Solid state (crystal or powder)
solution
Gas phase
What are hydantoinsandWhy hydantoins
•Hydantoin derivatives are well known for their medical applications, e.g. as:•antiepileptic drugs [D. Janz, Der Nervenarzt 21 (1950) 113; T. C. Butler, W. J. Waddell, J. Pharm. Exp.
Therapeut. 110 (1954) 120.] Phenytoin, Mephenytoin•Antiproliferative activity [C. S. A. Kumar, et al., Inv. New Drugs 27 (2009) 131;
C.V. Kavitha, et al., Biochem. Pharmacol. 77 (2009) 348.]•inhibition of aldosoreductase [R. Sarges, R. C. Schnur, J. L. Belletire, M. J. Peterson, J. Med. Chem. 31
(1988) 230.]•and potential application for treatment of HIV-1 infections [D. Kim, et al., Bioorg. Med.
Chem. Lett. 11 (2001) 3099.; D. Kim, et al., Bioorg. Med. Chem. Lett. 11 (2001) 3103.].
NN
Y
XR2
R1
H
H1
2
345
X, Y = O or Simidazolidineimidazolidine--2,42,4--dionedione(by IUPAC)(by IUPAC)
Metal-ion coordination ability,Biological activity,
BUTCorrect structure – for correct conclusions !!!!
Hydantoins vs thio-hydantoins
NH
HN S
S
CX8 01
NH
HNS
S
CX10002n = 2 - 5; 3 - 6
Structure of the studied Spiro-dithio-hydantoins
N
N
S
S
H
H(CH2)n
1
2
345
The crystal structure of the non-coordinated dithio-hydantoinsis available
However,none of their metal complexes could be crystallized
Biologicalactivity
Spectroscopicproperties
Biologicalactivity
structureSpectroscopicproperties
structure
Focus on the 13C NMR shifts of C2-, C4- and C5-carbon
atoms in the hydantoin ring
13C NM shielding constants (GIAO-B3LYP/6-31G**)Of the free ligands vs of the complexes
13C CPMAS NMR spectraOf the free ligands vs of the complexes
Gas-phase optimized structures (B3LYP/6-31G**)Of the free ligands vs models of the complexes
suggestThe best model structure of the complexes
1 A. Ahmedova, P. Marinova, K. Paradowska, M. Marinov, I. Wawer, M. Mitewa, Polyhedron 29 (2010) 1639-1645.2 A. Ahmedova, P. Marinova, K. Paradowska, N. Stoyanov, I. Wawer, M. Mitewa, Inorg. Chim. Acta 363 (2010) 3919-3925.
Infinite H-bond network in the crystal structures of compounds 2 – 6
All C2=S2 groupsare involved in 2 inter-molecular H bondings
C4=S4 groups do not form inter-molecular H bonds
All N-H groups participate in inter-molecular H bonds
INTERMOLECULAR INTERACTIONS AND THE CONSEQUENCES
Expected stronger H bonds in the solid state than in solutionand
Elongation of the corresponding bondsand
Less shielding of the corresponding C atoms
!!! Pay attention to the non-innocent role of the solvent
13C CPMAS NMR spectrum
13C NMR shifts in ppm in solid state and in DMSO
1
2
345
N
N
S
S
H
H6
78
9
1011 12
213.1 180.2 81.5
cy8
35.9 – 25.1
13C NMR shifts in DMSO
212.7 179.6 78.4 34.9 – 20.8
1
2
345
N
N
S
S
H
H
678
910 11
13C CPMAS NMR spectrum
211.8
cy7
40.2 – 22.9177.6
213.5 179.6 40.1 – 22.1
13C NMR shifts in ppm in solid state and in DMSO
13C NMR shifts in DMSO
79.1
81.1
1
2
345
N
N
S
S
H
H6
7
89
10
13C CPMAS NMR spectrumcy6
13C NMR shifts in ppm in solid state and in DMSO
13C NMR shifts in DMSO
209.2 178.8 79.540.2 - 23.0
211.8 180.0 77.1 36.7 – 20.8
13C NMR shifts in ppm in solid state and in DMSO
13C NMR shifts in DMSO
13C CPMAS NMR spectrumcy5
212.5179.3
83.341.8 25.3
210.0178.0
85.545.5;42.0
27.8;25.4
209.6
178.929.325.4
84.1
42.3
in CDCl3
NH
HN S
S
280 260 240 220 200 180 160 140 120 100 80 60 40 20 ppm
** * * * *
C4 C2 C5
13C NMR shifts in ppm in solid state and in DMSO
13C NMR shifts in DMSO
13C CPMAS NMR spectrum
203.8 182.3
130.0 - 121.8
85.7
206.8 182.8
144.2 – 123.9
84.8
NO X-ray structure
13C CPMAS NMR spectrumcy4
13C NMR shifts in ppm in solid state and in DMSO
13C NMR shifts in DMSO
182.5 157.762.8
33.8 15.1
178.5 155.960.9
32.1 13.2
Powder diffraction data
Gas-phase modelsof crystal packing
Solid-statecalculations
Structure &13C NMR shiftsin gas phase
Structure & 13C NMR shiftsin solution (DMSO)
Solid-state 13C NMRSolution 13C NMR (DMSO)
Single crystal X-ray diffraction
EXPERIMENTAL DATA
CALCULATIONS
??? How do intermolecular interactions affect the structural and spectroscopic data ???
Compare structural parameters in the hydantoin ring13C NMR shifts of C2-, C4- and C5-carbon atoms
X-ray data vs gas-phase optimizations (B3LYP/6-31G**) ofisolated molecules and
trimers connected via intermolecular H bonding
13C NMR in DMSO-d6 vs calculated (GIAO-B3LYP/6-31G**) and in solid state shielding constants in gas phase(CPMAS) in DMSO media (IEF-PCM)
or of the optimised trimers
13C NMR shiftsC5 – 79.5 ppmCPMAS: C4 – 209.2 ppm C2 – 178.8 ppm
GIAO-DFT: C5 – 78.1 ppm C4 – 207.0 ppm C2 – 175.0 ppm
EXP in DMSOC5 – 77.1 ppmC4 – 211.8 ppmC2 – 180.0 ppm
CALC in DMSOC5 – 80.8 ppmC4 – 212.0 ppmC2 – 176.6 ppm
1.628 Å
1.665 Å
1.353 Å
1.382 Å
1.320 Å
X-ray data 1.646 Å
1.360 Å
1.398 Å
1.348 Å1.657 Å
Isol.mol.calc.
cy6
1.628 Å
1.665 Å
1.353 Å
1.382 Å
1.320 Å
X-ray data 1.645 Å
1.365 Å
1.333 Å1.689 Å
CALC Trimer
13C NMR shiftsC5 – 79.5 ppmCPMAS: C4 – 209.2 ppm C2 – 178.8 ppm
GIAO-DFT: C5 – 80.1 ppm C4 – 209.0 ppm C2 – 177.2 ppm
1.384 Å
cy6
13C NMR shiftsC5 – 81.1 ppmCPMAS: C4 – 211.8 ppm C2 – 177.6 ppm
GIAO-DFT: C5 – 79.8 ppm C4 – 209.2 ppm C2 – 174.2 ppm
EXP in DMSOC5 – 79.1 ppmC4 – 213.5 ppmC2 – 179.6 ppm
CALC in DMSOC5 – 82.6 ppmC4 – 214.0 ppmC2 – 175.8 ppm
1.626 Å
1.668 Å
1.349 Å
1.380 Å
1.317 Å
X-ray data 1.647 Å
1.360 Å
1.398 Å
1.347 Å
1.657 Å
Isol.mol.calc.
Cy7
1.626 Å
1.668 Å
1.349 Å
1.317 Å
X-ray data 1.645 Å
1.365 Å
1.331 Å1.689 Å
13C NMR shiftsC5 – 81.1 ppmCPMAS: C4 – 211.8 ppm C2 – 177.6 ppm
GIAO-DFT: C5 – 81.2 ppm C4 – 211.1 ppm C2 – 176.0 ppm
Cy7
CALC Trimer
1.384 Å1.380 Å
3D Calculations ☺
Calculation of periodic structures with DFT
Use of plane waves and ultrasoft pseudopotentials(GGA PBE functional)
The relaxed structures were used for the calculations of the nuclear magnetic resonance (NMR) chemical shifts of 13C nuclei via the GIPAW method (gauge-
including projector augmented wave )
Calculations were performed in the three main groups:•for isolated molecules•for layers•for bulk materials
The energies of the interaction between the molecules in the bulk Emb per one molecule were calculated using the following equation:
Emb=(Ebulk-Nb.Emol)/Nb
0 50 100 150 2000
50
100
150
200
250
R=0,9997
CPMAS 13C NMR shiftsQ
E c
alcu
late
d fo
r bul
k
cy6
0 50 100 150 200 2500
50
100
150
200
250
R=0,9998
QE
cal
cula
ted
for b
ulk
CPMAS 13C NMR shifts
cy7
0 20 40 60 80 100 120 140 160 180 2000
50
100
150
200
QE
cal
cula
ted
for b
ulk
CPMAS 13C NMR shifts
R=0,9995
cy4
NO single-crystal X-ray structure available
Solid-state (QE) calculations were usedto REFINE
the initial powder diffraction data
Acknowledgements
Prof. I. WawerDr. K. Paradowska Dr. R. Petrova
Dr. B. ShivachevDr. G.Pavlovic
Prof.Ana Proykova for calculation timeon PHYSON computer cluster
NATIONAL SCIENCE FUNDMinistry of Education and Science
NH
HN S
S
Get the solid-statestructure
Top Related