Cisplatin interacting with buffering media and cysteine: Molecular insight due to Raman microspectroscopy

• Published in: Journal of Raman spectroscopy 2019-04, Vol.50 (4), p.528-536
• Main Author: Šišková, Karolína M.
• Format: Article
• Language: English
• Subjects: 3‐(N‐morpholino)propanesulfonic acid; 4‐(2‐hydroxyethyl)‐1‐piperazineethanesulfonic acid; Amines; Ammonia; Biophysics; Buffers; Chemical bonds; Cisplatin; cis‐diammineplatinum(II) dichloride; Coordination; Covalent bonds; Crystals; Cysteine; Dissolution; Kinetics; Laser beams; Micrometers; Mopping; Raman spectra; Sodium chloride; Solvation; Spectroscopy; tris(hydroxymethyl)aminomethane; tromethamine
• ISSN: 0377-0486; 1097-4555
• DOI: 10.1002/jrs.5545

The solvation of cisplatin, [Pt(NH3)2Cl2], a widely used chemotherapeutical drug, regarded on molecular level in model media is often overlooked by researchers. It is, however, essential in several aspects. The solvation was monitored by using Raman scattering microspectroscopy. This technique being used for the first time enables us to focus the laser beam several micrometers above the dissolving crystals of cisplatin, allowing to monitor the process of cisplatin dissolution in situ. The obtained Raman microspectroscopic results provided a direct qualitative evidence about (a) interaction between Tris, MOPS, and HEPES buffers and cisplatin via PtN coordination covalent bond and (b) interaction of cisplatin with cysteine dominantly through PtS bond (at pH 7.4). Furthermore, this vibrational spectroscopic technique revealed a decreased dissolution of cisplatin in a particular buffering solution in the presence of NaCl abundance; kinetics of the PtN formation in the case of MOPS–NaCl medium was monitored. Moreover, spatial dissolution of cisplatin in Cys‐Tris medium was observed in situ. The particular buffering medium, containing either primary or tertiary amines, can interact with cisplatin via a coordination covalent bond. The presence of an increased NaCl concentration can partially suppress this interaction. Raman microspectroscopy, a method of vibrational spectroscopy, is a powerful technique to investigate the dissolution of cisplatin in situ. On the basis of vibrational microspectroscopic measurements, it provides direct evidence about cisplatin interactions with selected model media being widely used in biochemistry and biophysics. This interaction could influence the effectiveness of cisplatin as a drug. The solvation of cisplatin studied on molecular level was monitored by using Raman scattering microspectroscopy in model media. The spectroscopic results directly evidenced the interaction between the particular buffering medium (containing either primary or tertiary amines) and cisplatin via PtN coordination covalent bond. PtS bond (at pH 7.4) dominated in the interaction of cisplatin with cysteine.