Journal of Applied Spectroscopy, Vol. 83, No. 6, January, 2017 (Russian Original Vol. 83, No. 6, November–December, 2016) QUANTUM CHEMICAL STUDY OF THE SOLVENT EFFECT ON THE ANTICANCER ACTIVE MOLECULE OF IPROPLATIN: STRUCTURAL, ELECTRONIC, AND SPECTROSCOPIC PROPERTIES (IR, 1 H NMR, UV) N. Sadeghi, a R. Ghiasi, b* R. Fazaeli, c and S. Jamehbozorgi d UDC 539.143.43 The structural, electronic, and spectroscopic properties of the anticancer active molecule of iproplatin were investigated in the gas and liquid phases. Based on the polarizable continuum model (PCM), the solvent effect on the structural parameters, frontier orbitals, and spectroscopic parameters of the complex was investigated. The results indicate that the polarity of solvents plays a significant role in the structure and properties of the complex. 1 H and 13 C NMR chemical shifts were calculated using the Gauge-invariant atomic orbital (GIAO) method. Pt–Cl and Pt–OH bonds were investigated through a vibrational analysis. Moreover, time dependent density functional theory (TD-DFT) was used to calculate the energy, oscillatory strength, and wavelength absorption maximum (λ max ) of electronic transitions and its nature within the complex. Keywords: iproplatin, anticancer drug, 1 H NMR chemical shift, frontier orbitals analysis, solvent effect. Introduction. Numerous platinum(IV) complexes have undergone clinical trials; however, none have been verified to be used in the United States so far [1–6]. A benefit of Pt(IV) complexes over their Pt(II) analogues is their six-coordinate octahedral coordination geometry. Being complexes of d 6 octahedral metal ions, Pt(IV) compounds are significantly more robust than those of Pt(II). Unwanted side reactions with proteins or intracellular thiols can usually be avoided by Pt(IV) complexes. Since Pt(IV) complexes are inert, they regularly undergo reduction to Pt(II) prior to binding to their final intracellular target, DNA [7]. Reduction of Pt(IV) happens with the loss of two ligands, providing a square-planar geometry for the Pt(II) product. One such complex that has been widely investigated clinically is iproplatin (cis,trans,cis-[PtCl 2 (OH) 2 (isopropylamine) 2 ] (CHIP). Iproplatin is synthesized by the reaction of cis-[Pt(i-PrNH 2 ) 2 Cl 2 ] with H 2 O 2 in water [8]. It was primarily chosen for clinical study due to its sole structure, high solubility, broad spectrum of activity, and lower toxicity compared to cisplatin [9]. There is initial indication that iproplatin has some activity against breast cancer [10]. The elevated solubility and inertness of iproplatin possibly permits for distribution in the body before the reduction to Pt(II). For example, techniques such as 195 Pt NMR illustrate that ascorbate reduces these Pt(IV) to Pt(II) complexes [11]. In this research, we illustrate the structural, electronic and spectroscopic (IR, UV, and 1 H NMR) properties of the active anticancer molecule of iproplatin in the gas phase and in different solvents. Computational Methods. All calculations were performed with Gaussian 09 suite software [12]. The calculations of the systems contain C, H, N, Cl, and O described by the standard 6-311G(d,p) basis set [13–16]. For Pt, the standard Def2- TZVPPD basis set [17] was used, and Pt described by the effective core potential (ECP) of Wadt and the Hay pseudo-potential [18]. Geometry optimization was carried out with the modified Perdew–Wang exchange and correlation (MPW1PW91) [19]. To verify that the optimization structures are minimal, harmonic vibrational frequencies were calculated. The population analysis was also performed by the natural bond orbital method [20] using NBO software. The electronic spectra for the studied complexes were calculated by TD-DFT [21] using the same hybrid functionals and basis sets as used for the optimization. The 20 lowest excitation energies were calculated. The GaussSum 2.2 software _____________________ * To whom correspondence should be addressed. a Arak Branch, Islamic Azad University, Arak, Iran; b East Tehran Branch, Islamic Azad University, Qiam Dasht, Tehran, Iran; e-mail: rezaghiasi1353@yahoo.com, rghiasi@iauet.ac.ir; c South Tehran Branch, Islamic Azad University, Tehran, Iran; d Hamedan Branch, Islamic Azad University, Hamedan, Iran. Published in Zhurnal Prikladnoi Spektroskopii, Vol. 83, No. 6, pp. 854–860, November–December, 2016. Original article submitted August 31, 2015. 0021-9037/17/8306-0909 ©2017 Springer Science+Business Media New York 909 DOI 10.1007/s10812-017-0383-9