Embed Size (px)
DESCRIPTION
Cisplatin Amino-acid Derivatives Oplatin (neutral) (ornithine-linked cisplatin) Shows preference to A over G Proven at the nucleoside and structural RNA level When binding to adenosine, two different isomers have been observed Chow Group and Rodgers Group, unpublished data Dalla Via, L.; Gia, O.; Magno, S. M.; Dolmella, A.; Marton, D.; Di Noto, V. Inorg Chim Acta 2006, 359, Glyplatin (deprotonated) (glycine-linked cisplatin) Simplicity and less flexibility Low computational cost
Citation preview
Frequency (cm-1)
Rel
ativ
e In
tens
ity
[Pt(Gly-H)Cl2]- IRMPD
Structural Determination and Evaluation of Theoretical Models and Basis Sets of
Cisplatin-Amino Acid Analoguesby IRMPD Action Spectroscopy
C.C. He,1 X. Bao,1 L. Hamlow,1 Y. Zhu,1 S. Strobehn,1 B. Kimutai,1 Y.-w. Nei,1 G. Berden,2 J. Gao,2 J. Oomens,2 C.S. Chow,1 and M.T. Rodgers1*
1 Department of Chemistry, Wayne State University, Detroit, MI 482022 FELIX facility, Radboud University, 6525 ED Nijmegen, The Netherlands
Cisplatin
Cisplatin[cis-diamminedichloroplatinum(II)]
• Anti-cancer drug• Chemical probe for structural
RNA• Resistance, neurotoxicity …
leavinggroups
carrierligands
• Carrier ligands determine the adduct profile
• Purine N7 position; G > A• Amino acids are great ligands
Lippert, B. Cisplatin : Chemistry and Biochemistry of a Leading Anticancer Drug; Verlag Helvetica Chimica Acta ;Wiley-VCH:ZurichBaik, M. H.; Friesner, R. A.; Lippard, S. J. J Am Chem Soc 2002, 124, 4495.
NH
N
NH2N
HN
O
guanine
N
N
NH2
NH
N
adenine
Cisplatin Amino-acid Derivatives
Oplatin (neutral)(ornithine-linked cisplatin)
• Shows preference to A over G• Proven at the nucleoside and
structural RNA level• When binding to adenosine, two
different isomers have been observed
Chow Group and Rodgers Group, unpublished dataDalla Via, L.; Gia, O.; Magno, S. M.; Dolmella, A.; Marton, D.; Di Noto, V. Inorg Chim Acta 2006, 359, 4197.
Glyplatin (deprotonated)(glycine-linked cisplatin)
• Simplicity and less flexibility• Low computational cost
ClO
Pt
H2N
H2N
O
Cl
Instrumentation
IRMPD yield = (SIf)/(Ip + SIf)
Polfer, N. C.; Oomens J., Phys. Chem. Phys. 2007, 9, 3804.
Sample:~1-7 mM Glyplatindissolved inMeOH:H2O (50:50)
no acid
(Infrared Multiple Photon Dissociation)IRMPD Action Spectroscopy
or OPO/OPA laser
IRMPD Mechanism
• Rapid intramolecular vibrational relaxation.
• Initially absorbed photon energy is distributed through the ion and is ready for the next photon absorption.
• The ion continues to absorb photons and redistribute that energy until the dissociation threshold is reached.
• IRMPD requires the absorption of tens to hundreds of photonsPolfer, N. C.; Oomens J., Mass Spectrometry Reviews, 2009, 28, 468– 494.
Hybrid Basis Sets
• Density Functional Theory MethodsB3LYP , CAM-B3LYP, LC-ωPBE, PBE0,
B3PW91, mPW1PW91,M06• Treatment of Platinum (Pt)
Effective Core PotentialAll-Electron Basis Sets
• Basis Sets for non-Metal AtomsPople, def2, Dunning
Gaussian 09, Revision D.01, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; et al. Gaussian, Inc., Wallingford CT, 2009.Paschoal, D.; Marcial, B. L.; Lopes, J. F.; De Almeida, W. B.; Dos Santos, H. F. J Comput Chem 2012, 33, 2292.de Berredo, R. C.; Jorge, F. E. J Mol Struc-Theochem 2010, 961, 107.de Berredo, R. C.; Jorge, F. E.; Jorge, S. S.; Centoducatte, R. Comput Theor Chem 2011, 965, 236.Malik, M.; Michalska, D. Spectrochim Acta A 2014, 125, 431.EMSL Basis Set Exchange https://bse.pnl.gov/bse/portal
Basis Set for non-Metal Atoms
EMSL Basis Set Exchange https://bse.pnl.gov/bse/portalGaussian 09
6-31G def2-SVP cc-pVDZ6-31G(d) aug-cc-pVDZ6-31+G(d)6-31+G(d,p)6-311+G(d,p) def2-TZVP cc-pVTZ6-311++G(d,p) def2-TZVPPD aug-cc-pVTZ6-311+(2d,2p)6-311+(3df,3dp)
def2-QZVPdef2-QZVPPD
cc-pVQZaug-cc-pVQZ
Pople def2 (Ahlrichs) DunningDouble Zeta
Triple Zeta
Quadruple Zeta
Frequency (cm-1)1000 1500 3000 3500
0
300
600
900
0
20
40
600.0
0.4
0.8
1.2
1.6
0.0
0.2
0.4
Rel
ativ
e In
tens
ity
0
300
600
900
0
10
20
[Pt(Gly-H)Cl2]- IRMPD
Frequency (cm-1)1000 1500 3000 3500
0
300
600
900
0
10
20
[Pt(Gly-H)Cl2]- NO binding
[Pt(Gly-H)Cl2]- OO binding
[Pt(Gly-H)Cl2]- O binding
IRMPD Experiment for Glyplatin
B3LYP/def2-TZVPPDPt: def2 ECP(Effective Core Potential)Scaling Factor: 0.98/0.95
x 5
6-31G 6-31G(d) 6-31+G(d)6-31+G(d,p)6-311+G(d,p)6-311++G(d,p) 6-311+G(2d,2p) 6-311+G(3df,3pd)Experimental
Frequency(cm-1)1000 1500 3000 3500
Rel
ativ
e In
tens
ity
0
400
800
1200
1600[Pt(Gly-H)Cl2]-
Basis Sets Evaluation for Glyplatin
B3LYP/LANL2DZ/varying Pt:LANL2DZ ECP
x 5
Frequency (cm-1)1000 1500 3000 3500
Rel
ativ
e In
tens
ity
0
300
600
900 [Pt(Gly-H)Cl2]- IRMPD
Conclusions
•Best result with the lowest cost: B3LYP/mDZP/def2-TZVP•Selected based on structural information, not necessarily good for energetic description
x 5
Frequency(cm-1)
1000 1200 1400 1600 18000.0
0.6
1.2
1000 1200 1400 1600 1800
0.0
0.1
0.2
[Pt(Gly-H)Cl2]-
[Pt(Orn)Cl]+
Frequency(cm-1)
1000 1200 1400 1600 1800
Rel
ativ
e In
tens
ity
0.0
0.4
0.8 [Pt(Lys)Cl]+
Sidechain Effects
ClO
Pt
H2N
H3N
O
ClCl
ClO
Pt
H2N
O
Cl
ClO
Pt
H2N
O
ClCl
H3N
Professor M. T. RodgersProfessor Christine ChowRodgers group membersXun Bao and Bett Kimutai (Chow group)Dr. Cliff FrielerDr. Jos Oomens, Dr. Giel Berden and Juehan GaoFELIX supporting staffCLIO User Facility staff
National Science FoundationDepartment of Chemistry
Acknowledgements
WSU C&IT
FELIX Facility
CLIO User Facility
![S-1 plus cisplatin versus fluorouracil plus cisplatin in ... · AGC patients included cisplatin, fluorouracil, oxaliplatin, irinotecan and taxane [3, 9-12]. S-1 is one of the oral](https://img.pdfslide.net/doc/110x75/60a5bdbe5dedbc68f44d7cf1/s-1-plus-cisplatin-versus-fluorouracil-plus-cisplatin-in-agc-patients-included.jpg)
