Arginine (Arg) complexes with Zn 2+ and Cd 2+ were examined by infrared multiple photon dissociation (IRMPD) action spectroscopy using light from a free electron laser. Electrospray ionization generated complexes of deprotonated Arg with Zn 2+ , [Zn(Arg–H)] + , and Arg with CdCl + , CdCl + (Arg). Possible low-energy conformers of these species were found using quantum chemical calculations, and their calculated IR spectra were compared to experimentally measured IRMPD spectra. Calculations were performed at the B3LYP/6-311+G(d,p) level for Zn 2+ complexes and B3LYP/def2-TZVP with an SDD effective core potential on cadmium for CdCl + complexes. [Zn(Arg–H)] + was found to adopt a charge-solvated, tridentate [N,CO − ,N ω ′] structure where Zn 2+ binds to the backbone amine, carbonyl oxygen, and side-chain terminal guanidine nitrogen (N ω ′). The CdCl + (Arg) species was suggested to be a mixture of a dominant (∼85%) charge-solvated, tridentate [N,CO,N ω ′] structure where the CdCl + binds to the backbone amine, carbonyl, and side-chain imine (N ω ′) and a minor (∼15%) bidentate [N,CO − ](N ω ′H 2 + ) zwitterionic structure where the metal center binds to the backbone amine and carbonyl oxygen with intramolecular proton migration from the hydroxyl to the N ω ′ guanidine nitrogen (as designated in parenthesis).
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Structural determination of arginine-linked cisplatin complexes via IRMPD action spectroscopy: arginine binds to platinum via NO − binding mode
Cisplatin, (NH 3 ) 2 PtCl 2 , has been known as a successful metal-based anticancer drug for more than half a century. Its analogue, Argplatin, arginine-linked cisplatin, (Arg)PtCl 2 , is being investigated because it exhibits reactivity towards DNA and RNA that differs from that of cisplatin. In order to understand the basis for its altered reactivity, the deprotonated and sodium cationized forms of Argplatin, [(Arg-H)PtCl 2 ] − and [(Arg)PtCl 2 + Na] + , are examined by infrared multiple photon dissociation (IRMPD) action spectroscopy in the IR fingerprint and hydrogen-stretching regions. Complementary electronic structure calculations are performed using density functional theory approaches to characterize the stable structures of these complexes and to predict their infrared spectra. Comparison of the theoretical IR spectra predicted for various stable conformations of these Argplatin complexes to their measured IRMPD spectra enables determination of the binding mode(s) of Arg to the Pt metal center to be identified. Arginine is found to bind to Pt in a bidentate fashion to the backbone amino nitrogen and carboxylate oxygen atoms in both the [(Arg-H)PtCl 2 ] − and [(Arg)PtCl 2 + Na] + complexes, the NO − binding mode. The neutral side chain of Arg also interacts with the Pt center to achieve additional stabilization in the [(Arg-H)PtCl 2 ] − complex. In contrast, Na + binds to both chlorido ligands in the [(Arg)PtCl 2 + Na] + complex and the protonated side chain of Arg is stabilized via hydrogen-bonding interactions with the carboxylate moiety. These findings are consistent with condensed-phase results, indicating that the NO − binding mode of arginine to Pt is preserved in the electrospray ionization process even under variable pH and ionic strength.
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- NSF-PAR ID:
- 10383322
- Date Published:
- Journal Name:
- Physical Chemistry Chemical Physics
- Volume:
- 23
- Issue:
- 38
- ISSN:
- 1463-9076
- Page Range / eLocation ID:
- 21959 to 21971
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d1cp03407c
