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We previously demonstrated that the δ NMR chemical shift of central NMR active atoms (A), in simple halido [AXn] (A=C, Si, Ge, Sn, Pb, Pt; Xn = combination of n halides, n = 4 or 6) derivatives, could be directly related to X radii overall sum, Σ(r L ). Further correlation have also been observed for tetrahedral [AX4] (A=C, Si; X4 = combination of four halides) compounds where the X Pauling electronegativities sum, Σ ( χ L Pau ) , $\Sigma (\chi _L^{{\rm{Pau}}}),$ exceeds a specific value (≈12.4). In this work, we focused on these latter systems considering the H vs. X substitution. The analysis of the literature reported δ(13C) and δ(29Si) NMR chemical shift for the mono hydrogenated derivatives and in particular for [CHF3] and [SiHF3], characterized by the lowest Σ(r L ) and the highest Σ ( χ L Pau ) , $\Sigma (\chi _L^{{\rm{Pau}}}),$ suggests a revised value for the H electronegativity ranking with respect to Pauling’s.

The series of complexes of formula [PtCl(η 2 -olefin)( N^N )] + , previously investigated for N^N = N , N , N′ , N′ -tetramethyl-ethylenediamine (Me 4 en), has been extended to the case of aromatic diimines 1,10-phenanthroline (phen) and 3,4,7,8-tetramethyl-1,10-phenanthroline (Me 4 phen) and to a variety of olefins (ethene, propene and styrene). The complexes have been prepared by reaction of the [PtCl 3 (η 2 -olefin)] − anions (K[PtCl 3 (η 2 -styrene)] reported here for the first time) with N^N in basic methanol. The initial [PtCl{η 1 -CH 2 CH(R′) OMe}( N^N )] (R′ = Me, Ph) complexes are formed in quantitative yield and as pure Markovnikov isomer. The reaction of the alkoxylic species with non coordinating acids, results in the quantitative formation of the desired cationic π-olefin complexes [PtCl(η 2 -olefin)( N^N )] + . The phenanthroline ligand confers peculiar properties to the new compounds. In particular, by reaction with triethylamine, [PtCl{η 2 -CH 2 CH(Me)}( N^N )] + species, undergo deprotonation of the olefin and formation of the dimeric species [{PtCl( N^N )} 2 ( μ -η 1 :η 2 -CH 2 CH CH 2 )] + which could be isolated and characterized. Interestingly such product in acetonitrile gives a disproportionation with precipitation of [PtCl 2 (phen)] and formation in solution of the new η 3 -allyl complex [Pt(η 3 -C 3 H 5 )(phen)]ClO 4 .

Starting from the [PtCl(η1-C2H4OMe)(phen)] (phen = 1,10-phenanthroline, 1) platinum(II) precursor, we synthesized and characterized by multinuclear NMR new [Pt(η1-C2H4OMe)(L)(phen)]+ (L = NH3, 2; DMSO, 3) complexes. These organometallic species, potentially able to interact with cell membrane organic cation transporters (OCT), violating some of the classical rules for antitumor activity of cisplatin analogues, were evaluated for their cytotoxicity. Interestingly, despite both complexes 2 and 3 resulting in greater cell uptake than cisplatin in selected tumor cell lines, only 3 showed comparable or higher antitumor activity. General low cytotoxicity of complex 2 in the tested cell lines (SH-SY5Y, SK-OV-3, Hep-G2, Caco-2, HeLa, MCF-7, MG-63, ZL-65) appeared to depend on its stability towards solvolysis in neutral water, as assessed by NMR monitoring. Differently, the [Pt(η1-C2H4OMe)(DMSO)(phen)]+ (3) complex was easily hydrolyzed in neutral water, resulting in a comparable or higher cytotoxicity in cancer cells with respect to cisplatin. Further, both IC50 values and the uptake profiles of the active complex appeared quite different in the used cell lines, suggesting the occurrence of diversified biological effects. Nevertheless, further studies on the metabolism of complex 3 should be performed before planning its possible use in tissue- and tumor-specific drug design.

The reactivity of [PtX2(Me2phen)] complexes (X = Cl, Br, I; Me2phen = 2,9-dimethyl-1,10-phenanthroline) with terminal alkynes has been investigated. Although the dichlorido species [PtCl2(Me2phen)] exhibits negligible reactivity, the bromido and iodido derivatives lead in short time to the formation of five-coordinate Pt(II) complexes of the type [PtX2(Me2phen)(η2-CHuCR)] (X = Br, I; R = Ph, n-Bu), in equilibrium with the starting reagents. Similar to analogous complexes with simple acetylene, the five coordinate species can also undergo dissociation of an halido ligand and formation of the transient square-planar cationic species [PtX(Me2phen)(η2-CHuCR)]+. This latter can further evolve to give an unusual, sparingly soluble square planar product where the former terminal alkyne is converted into a :CvC(H)(R) moiety with the α-carbon bridging the Pt(II) core with one of the two N-donors of coordinated Me2phen. The final product [PtX2{κ2-N,C-(Z)-N̲1–N10–C̲vC(H)(R)}] (N1–N10 = 2,9-dimethyl-1,10-phenanthroline; X = Br, I) contains a Pt–N–C–C–N–C six-membered chelate ring in a square planar Pt(II) coordination environment.

In this work, we assessed the capacity of RNA polymerases to use platinated ribonucleotides as substrates for RNA synthesis by testing the incorporation of the model compound [Pt(dien)(N7-5'-GTP)] (dien=diethylenetriamine; GTP=5'-guanosine triphosphate) into a natural RNA sequence. The yield of in vitro transcription operated by T7 RNA polymerase, on the LacZ (Escherichia coli gene encoding for β-galactosidase) sequence, decreases progressively with decreasing the concentration of natural GTP, in favor of the platinated nucleotide, [Pt(dien)(N7-5'-GTP)]. Comparison of the T7 RNA polymerase transcription activities for [Pt(dien)(N7-5'-GTP)] compound incorporation reaction test, with respect to the effect of a decreasing concentration of natural GTP, showed no major differences. A specific inhibitory effect of compound [Pt(dien)(N7-5'-GTP)] (which may pair the complementary base on the DNA strand, without being incorporated in the RNA by the T7 RNA polymerase) was evidenced. Our findings therefore suggest that RNA polymerases, unlike DNA polymerases, are unable to incorporate N7-platinated nucleotides into newly synthesized nucleic acids. In this respect, specifically designed N7-platinated nucleotides based compounds could be used in alternative to the classical platinum based drugs. This approach may offer a possible strategy to target specifically DNA, without affecting RNA, and is potentially able to better modulate pharmacological activity.

In this work, we show by a simple empirical approach that a linear relationship between observed 195Pt NMR frequencies and the overall sum of the ionic radii of the coordinated halido ligands [Σ(rh)] exists in square-planar PtII complexes of the type [PtXnY4–n]2– (1 ≤ n ≤ 4; X, Y = Cl, Br, I). Another finding was that such square-planar complexes could be empirically described as octahedral complexes, with the two lobes of the 5dz² orbital above and below the coordination plane acting as two pseudo-halido ligands, each showing a constant apparent radius of around 207 pm. According to our approach, the overall apparent radius of around 415 pm produces constant 195Pt NMR shielding for all [PtXnY4–n]2– complexes of about 10450 ppm. This result is 1) consistent with the theoretically calculated overall 5d shell lone-pair shielding observed in square-planar PtII with respect to octahedral PtIV complexes and 2) almost coincident with the already measured chemical shift anisotropy (CSA) of the K2[PtCl4] complex both in solution and in the solid state (single crystal).

The relevant adsorption of cis -[Pt(NH 3 ) 2 (P 2 O 7 )] 2 − ( phosphaplatin ) on hydroxyapatite nanocrystals (nHAP) was observed and studied in water suspension. Phosphaplatin cytotoxicity, which is very low for HeLa, MCF-7 and HS-5 cell lines could be enhanced, reaching that of cisplatin , by interaction with solid nHAP. This effect stems from nHAP ability to catalyze the phosphaplatin hydrolysis, producing the same hydrolytic species responsible for cisplatin antitumor activity.