Application of flavonoids – quercetin and rutin – as new matrices for matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometric analysis of Pt(II) and Pd(II) complexes

Attempts are being made to overcome the resistance of tumour cells to platinum (Pt) drugs by the synthesis of new generations of Pt complexes, and it is important to find appropriate and simple methods for the characterization of those novel complexes. The additional applicability of such a method for the analysis of the interactions of metal complexes with biomolecules would be advantageous. Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS) seems to possess the capability to become this method of choice, since it could be applied to low‐mass complexes as well as for the analysis of large biomolecules. In this work the applicability of flavonoids – quercetin and rutin – as matrices for MALDI‐TOFMS analysis of dichlorido(ethylendiamine)platinum(II) ([PtCl₂(en)]), dichlorido(diaminocyclohexane)platinum(II) ([PtCl₂(dach)]) and chloride (diethylenetriamine) palladium(II) chloride ([PdCl(dien)]Cl) complexes is demonstrated. Spectra of Pt(II) and Pd(II) complexes recorded in the presence of quercetin and rutin are rather simple: Pt(II) complexes generate [M+Na]⁺ or [M+K]⁺ions, whereas the investigated Pd(II) complex gives ions generated by the loss of one Cl^? or HCl. Flavonoids give a relatively small number of well‐defined ions in the low‐mass region (at m/z 303.3 for quercetin and m/z 633.5 for rutin). Quercetin and rutin can be applied in much lower concentrations than other common MALDI matrices and require rather low laser intensity. We speculate that flavonoids stabilize the structures of the metal complexes and that they may be useful for the analysis of other biologically active metal complexes, thus implying their broader applicability. Copyright © 2009 John Wiley & Sons, Ltd.     

Synthesis,physico-chemical characterization and bioevaluation of Ni(II), Pd(II), and Pt(II) complexes with 1-(o-tolyl)biguanide: Antimicrobial and antitumor studies

New complexes of type [M(tbg)₂]Cl₂ [tbg = 1-(o-tolyl)biguanide; M = Ni(II), Pd(II), and Pt(II)] were synthesized and characterized to develop new biologically active compounds. The features of the complexes were assigned from microanalytical and thermal data. The NMR, FT-IR, and UV-Vis spectra were established by comparison with HtbgCl. All complexes exhibit a square-planar geometry resulting from the chelating behavior of tbg. The HtbgCl and [Ni(tbg)₂]Cl₂ complexes were fully characterized by single-crystal X-ray diffraction. The HtbgCl species crystallize in the monoclinic C2/c spatial group, while the Ni(II) complex adopts an orthorhombic Pna2₁ spatial group. The structure is stabilized by a complex hydrogen bonds network. The in vitro antimicrobial assays revealed improved antimicrobial activity for complexes in comparison with the ligand against both planktonic and biofilm embedded microbial cells. The most efficient compound, showing the largest spectrum of antimicrobial activity, including Gram-positive and Gram-negative bacteria, as well as fungal strains, in both planktonic and biofilm growth states was the Pd(II) complex, followed by the Pt(II) complex. The Pt(II) compound exhibited the most significant antiproliferative activity on the human cervical cancer SiHa cell line, inducing a cell cycle arrest in the G2/M phase.     

3,6-bis(2′,-pyridyl)pyridazine dinuclear complexes: Palladium(II), platinum(II) and first row transition metal(II) mixed complexes

New Pd(II) and Pt(II) 3,6-bis(2′-pyridyl)pyridazine (dppn) mononuclear complexes of the type M(dppn)Cl₂ were prepared and characterized. From M(dppn)Cl₂, the bimetallic homonuclear complexes M(dppn)MCl₄ were prepared by reaction with Pd(PhCN)₂Cl₂ or K₂PtCl₄. Bimetallic heteronuclear species of the type M(dppn)M′Cl₄, were prepared reacting the mononuclear complexes with the stoichiometric amount of M′Cl₂ (M′ = Cu, Co, Ni). All the described reaction give product in high yield. The isolated compounds, almost completely insoluble in most organic solvents, were characterized by elemental analysis, IR, ESR, reflectance spectra, and magnetic moment measurements. On the basis of these data the geometries around the metals are discussed.     

Identification of Pt(II) and Pd(II) stereoisomeric complexes with aminobutyric acid by NMR and IR spectroscopy

Complexes of Pd(II) with aminobutyric acid AmH = NH₂CH(CH₂CH₃)COOH, namely, trans-[Pd(AmH)₂Cl₂] with monodentate (via the NH₂ group) AmH ligands and cis-, trans-Pd(Am)₂ with bidentate (via NH₂ and COO groups) ligands have been synthesized for the first time. Elemental analysis and IR and NMR spectroscopy were used to identify the synthesized compounds. The NMR spectra of the Pd(II) complexes were interpreted by comparing them with the NMR spectra of the analogous complexes of Pt(II). For Pt(II) and Pd(II) complexes with aminobutyric acid used as examples, an approach to identification of diastereomer bis-aminoacid complexes in specimens with racemic aminoacids by NMR spectroscopy is demonstrated.     

Spectral,crystallographic, theoretical and antibacterial studies of palladium(II)/platinum(II) complexes with unsymmetric diphosphine ylides

The reaction of α‐keto‐stabilized diphosphine ylides [Ph₂P(CH₂)_nPPh₂═C(H)C(O)C₆H₄‐p‐CN] (n = 1 (Y¹); n = 2 (Y²)) with dibromo(1,5‐cyclooctadiene) palladium(II)/platinum(II) complexes, [Pd/PtBr₂(cod)], in equimolar ratio gave the new cyclometalated Pd(II) and Pt(II) complexes [Br₂Pd(κ²‐Y¹)] ( 1 ), [Br₂Pt(κ²‐Y¹)] ( 2 ), [Br₂Pd(κ²‐Y²)] ( 3 ) and [Br₂Pt(κ²‐Y²)] ( 4 ). These compounds were screened in a search for novel antibacterial agents and characterized successfully using Fourier transfer infrared and NMR (¹H, ¹³C and ³¹P) spectroscopic methods. Also, the structures of complexes 1 and 2 were characterized using X‐ray crystallography. The results showed that the P,C‐chelated complexes 1 and 2 have structures consisting of five‐membered rings, while 3 and 4 have six‐membered rings, formed by coordination of the ligand through the phosphine group and the ylidic carbon atom to the metal centre. Also, a theoretical study of the structures of complexes 1 – 4 was conducted at the BP86/def2‐SVP level of theory. The nature of metal–ligand bonds in the complexes was investigated using energy decomposition analyses (EDA) and extended transition state combined with natural orbitals for chemical valence analyses. The results of EDA confirmed that the main portions of ΔE_int, about 57–58%, in the complexes are allocated to ΔE_elstat.     

Platinum and Palladium Complexes Bearing New (1R,2R)‐(–)‐1,2‐Diaminocyclohexane (DACH)‐Based Nitrogen Ligands: Evaluation of the Complexes Against L1210 Leukemia

The reaction of (1R,2R)‐(–)‐1,2‐diaminocyclohexane ( 1 ) [DACH] with the aldehyde (1R)‐(–)‐myrtenal ( 2 ) in MeOH afforded the bidentate diimine ligand, (1R,2R)‐(–)‐N¹,N²‐bis{(1R)‐(–)myrtenylidene}‐1,2‐diaminocyclohexane ( 3 ) in a high yield. Reduction of 3 using LiAlH₄ led to the formation of the desired ligand ( 4 ) (1R,2R)‐(–)‐N¹,N²‐bis{(1R)‐(–)myrtenyl}‐1,2‐diaminocyclohexane. Treatment of compound 4 with K₂PtCl₄ or K₂PdCl₄ yielded the corresponding platinum(II) and palladium(II) complexes, Pt‐5 and Pd‐6 , respectively. The reaction of compound 3 with K₂PtCl₄ gave the diimine complex Pt‐7 . The cytotoxic activity of the complexes Pt‐5 , Pd‐6 and Pt‐7 was tested and compared to the approved drugs, cisplatin ( Cis ‐Pt ) and oxaliplatin ( Ox‐Pt ). The complexes ( Pt‐5 , Pd‐6 and Pt‐7 ) inhibit L1210 cell line proliferation with an IC₅₀ of 0.6, 4.2, and 0.7 μL, respectively as evidenced by measuring thymidine incorporation.     

Synthesis and characterization of polymeric Pd(II), Pt(IV), and Au(III) complexes of 2,2′-(1,4-phenylenedivinylene)-bis-8-hydroxyquinoline

The complexes of 2,2′-(1,4-Phenylenedivinylene)-bis-8-hydroxyquinoline (LH₂) with K₂PdCl₄, H₂PtCl₆ and HAuCl₄ were synthesized and characterized with ¹H-and ¹³C-NMR, elemental analysis, FT-IR, and molar conductivity. Au(III) and Pt(IV) complexes have characteristic conductance, while the Pd(II) complex has a non-ionic structure according to the molar conductivity and elemental analysis. This text was submitted by authors in English.     

Tin(II) Halide Insertion or Halogen Exchange in the Reactions of Dihaloplatinum(II) Complexes with Tin(II) Halide

Reactions of SnCl₂ with the complexes cis‐[PtCl₂(P₂)] (P₂=dppf (1,1′‐bis(diphenylphosphino)ferrocene), dppp (1,3‐bis(diphenylphosphino)propane=1,1′‐(propane‐1,3‐diyl)bis[1,1‐diphenylphosphine]), dppb (1,4‐bis(diphenylphosphino)butane=1,1′‐(butane‐1,4‐diyl)bis[1,1‐diphenylphosphine]), and dpppe (1,5‐bis(diphenylphosphino)pentane=1,1′‐(pentane‐1,5‐diyl)bis[1,1‐diphenylphosphine])) resulted in the insertion of SnCl₂ into the Pt? Cl bond to afford the cis‐[PtCl(SnCl₃)(P₂)] complexes. However, the reaction of the complexes cis‐[PtCl₂(P₂)] (P₂=dppf, dppm (bis(diphenylphosphino)methane=1,1′‐methylenebis[1,1‐diphenylphosphine]), dppe (1,2‐bis(diphenylphosphino)ethane=1,1′‐(ethane‐1,2‐diyl)bis[1,1‐diphenylphosphine]), dppp, dppb, and dpppe; P=Ph₃P and (MeO)₃P) with SnX₂ (X=Br or I) resulted in the halogen exchange to yield the complexes [PtX₂(P₂)]. In contrast, treatment of cis‐[PtBr₂(dppm)] with SnBr₂ resulted in the insertion of SnBr₂ into the Pt? Br bond to form cis‐[Pt(SnBr₃)₂(dppm)], and this product was in equilibrium with the starting complex cis‐[PtBr₂(dppm)]. Moreover, the reaction of cis‐[PtCl₂(dppb)] with a mixture SnCl₂/SnI₂ in a 2 : 1 mol ratio resulted in the formation of cis‐[PtI₂(dppb)] as a consequence of the selective halogen‐exchange reaction. ³¹P‐NMR Data for all complexes are reported, and a correlation between the chemical shifts and the coupling constants was established for mono‐ and bis(trichlorostannyl)platinum complexes. The effect of the alkane chain length of the ligand and Sn^II halide is described.     

Further Studies of Nitrodithioacetates of Ni(II), Pd(II) and Pt(II)

Abstract

Ni(II), Pd(II), and Pt(II) complexes of NO₂CHCS₂ ^?2 have been prepared, and their i.r and u.v spectra described. Spectroscopic evidence is presented to substantiate the existence of the new species K₂Ni(NO₂CHCS₂)₂S, a dithio-perthio carboxylate complex.     

Synthesis and characterization of a new platinum(II) complex with L-mimosine

Synthesis and characterization of a new Pt(II)–mimosine complex are described. Elemental, mass spectrometry and thermal analyses for the complex are consistent with the formula [PtCl₂(C₈H₁₀N₂O₄)]·1.5H₂O. ¹³C NMR, ¹⁵N NMR and infrared spectroscopy indicate coordination of the ligand to Pt(II) through the N and O atoms in a square-planar geometry. The final residue after thermal treatment was identified as metallic Pt. The complex is soluble in dimethylsulfoxide.     

Structures and optical and electrochemical properties of the Pt(II) and Pd(II) complexes with cyclometallated 2-phenylbenzothiazole and 1,4,7-trithiocyclononane

The distorted square pyramidal structures of the Pt(II) and Pd(II) complexes with cyclometallated 2-phenylbenzothiazole and flexible 1,4,7-trithiocyclononane are shown by X-ray diffraction analysis, IR spectroscopy, and ¹Н, ¹³С{¹H{, and ¹⁹⁵Pt NMR spectroscopy. The axial interaction of the d _Z2 orbital of Pt(II) and Pd(II) with the S atom of 1,4,7-trithiocyclononane results in the temperature quenching of the intraligand phosphorescence of the cyclometallated complexes in a solution and the one-electron ligand- and metal-centered reduction and oxidation of the complexes with the formation of the relatively stable Pd(III) complex (CIF file CCDC no. 1483011).     

The preparation and electrochemistry of gold(III), palladium(II) and platinum(II) complexes with 2-(diphenylphosphino)thiobenzene: X-ray crystal structure of [Au(Ph2PC6H4S)(Ph2][BPh4]

Summary Tetrachloroaurate(III) reacts with two equivalents of the bidentate (1-) mixed phosphinothiol ligand 2-(diphenylphosphino)benzenethiol (DPPBTH) in mildly alkaline MeOH to give a cation that can be precipitated from solution as the tetraphenylborate salt, the title complex [Au(DPPBT)₂][BPh₄] (1). The X-ray crystal structure of the complex shows it has a square planar geometry. K₂[PtCl₄] or PtCl₄ react with DPPBTH in mildly alkaline MeOH to give the 16 electron platinum(II) complex [Pt(DPPBT)₂] (2), whilst reaction of Na₂[PdCl₄] with DPPBTH under similar conditions gives the 16 electron palladium complex [Pd(DPPBT)₂] (3). The complexes have been studied by u.v., i.r. and n.m.r. The electrochemical behaviour of complex (1) was also investigated. Bis-[2-(diphenylphosphino)benzenethiolato]aurate(III).     

Platinum(II) and platinum(IV) complexes of 2-amino-4, 6-dimethylpyrimidine

Summary Platinum(II) and platinum(IV) complexes of 2-amino-4, 6-dimethylpyrimidine, ADMPY, have been prepared. Solids of formula Pt(ADMPYH⁺)Cl₃, Pt(ADMPY)₂Cl₄ and Pt(ADMPY)₂Cl₄·2HCl have been isolated and characterized by elemental analyses in conjuction with i.r. and n.m.r. spectra. A paramagnetic tan to reddishbrown complex has been reproducibly prepared from the direct reaction of K₂PtCl₄ and ADMPY at pH 6.     

Synthesis and anticancer activity of chalcogenide derivatives and platinum(II) and palladium(II) complexes derived from a polar ferrocene phosphanyl–carboxamide

The polar phosphanyl‐carboxamide, 1′‐(diphenylphosphanyl)‐1‐[N‐(2‐hydroxyethyl)carbamoyl]ferrocene ( 1 ), reacts readily with hydrogen peroxide and elemental sulfur to give the corresponding phosphane‐oxide and phosphane‐sulfide, respectively, and with platinum(II) and palladium(II) precursors to afford various bis(phosphane) complexes [MCl₂( 1 ‐κP)₂] (M = trans‐Pd, trans‐Pt and cis‐Pt). The anticancer activity of the compounds was evaluated in vitro with the complexes showing moderate cytotoxicities towards human ovarian cancer cells. Moreover, the biological activity was found to be strongly influenced by the stereochemistry, with trans‐[PtCl₂( 1 ‐κP)₂] being an order of magnitude more active than the corresponding cis isomer. Copyright © 2010 John Wiley & Sons, Ltd.     

NMR studies of transformations of Pt(II) and Pd(II) complexes with amino acids in solution. 1. Glycine complexes

¹H,¹³C, and¹⁹⁵Pt NMR studies were performed for Pt(ll) and Pd(II) complexes with glycine cis- and trans-M(Gly)₂, trans-Pd(GlyH)₂Cl₂ , cis- and trans-Pt(GlyH)₂Cl₂ , Na[Pd(GIy)Cl₂], and K[Pt(Gly)CI₂] in donor type solvents DMSO and H₂O. It is shown that a cis ↔ trans equilibrium takes place in these solvents and that the equilibration rate is low for Pt(II) complexes and high for Pd(II) complexes. Therefore, the cis- and trans-complexes of Pt(II) may be recorded by NMR spectroscopy in the individual state, whereas for Pd(II) there is an equilibrium mixture of cis- and trans-isomers. Solvolysis of Cl-containing complexes in DMSO is studied. A mechanism of solvolysis involving eis ↔ trans isomerization of the dichloro complexes of Pd(II) is suggested. NMR spectral data for some solvolysis products are given. Translated fromZhurnal Strukturnoi Khimii, Vol. 41, No. 2, pp. 300–311, March–April, 2000.     

Synthesis, Structure, and Antimicrobial Activity of Complexes of Pt(II), Pd(II), and Ni(II) with the Condensation Product of 2-(Diphenylphosphino)benzaldehyde and Semioxamazide

Complexes of Pt(II), Pd(II), and Ni(II) with the condensation derivative of 2-(diphenylphosphino)benzaldehyde and semioxamazide were synthesized, characterized, and their antimicrobial activity was evaluated. The ligand and the complexes were characterized by spectroscopic methods with the particular accent on NMR spectral analysis. For the palladium(II) complex, the crystal structure was determined by X-ray analysis. In all the complexes the ligand is coordinated as a tridentate via a P, N, O donor set. The Pd(II) and Pt(II) complexes have a square planar geometry, whereas the geometry of the Ni(II) complex is tetrahedral. The ligand showed antibacterial and antifungal activity, which was enhanced upon complexation.     

Synthesis, Structure, and Antimicrobial Activity of Complexes of Pt(II), Pd(II), and Ni(II) with the Condensation Product of 2-(Diphenylphosphino)benzaldehyde and Semioxamazide

Summary. Complexes of Pt(II), Pd(II), and Ni(II) with the condensation derivative of 2-(diphenylphosphino)benzaldehyde and semioxamazide were synthesized, characterized, and their antimicrobial activity was evaluated. The ligand and the complexes were characterized by spectroscopic methods with the particular accent on NMR spectral analysis. For the palladium(II) complex, the crystal structure was determined by X-ray analysis. In all the complexes the ligand is coordinated as a tridentate via a P, N, O donor set. The Pd(II) and Pt(II) complexes have a square planar geometry, whereas the geometry of the Ni(II) complex is tetrahedral. The ligand showed antibacterial and antifungal activity, which was enhanced upon complexation.     

Synthesis and characterization of mononuclear palladium(II) and platinum(II), dinuclear palladium(I) and platinum(I), and heterobimetallic (Pt-Hg or Pt-Ag) complexes containing 1,1-bis-(diphenylphosphino)ethane as ligand

Summary The complex [Pd(dpmMe)₂]Cl₂ [dpmMe = 1,1-bis-(diphenylphosphino) ethane] was prepared from [PdCl₂-(PhCN)₂], whilst [Pd₂X₂(-dpmMe)₂] complexes were prepared from [PdCl₂PhCN₂] and [Pd(PPh₃)₄] (X = Cl), [PdBr( ³-C₃H₅)]₂ (X = Br), or [Pd₂Cl₂(-dpmMe)₂] (X = I). Reaction of [Pd₂Cl₂(-dpmMe)₂] with MeO₂C-C523-01CCO₂Me(L) gave the A-frame complex [PdCl₂(-L) (-dpmMe)₂]. The complexes [PtCl₂(dpmMe)] and [Pt(dpmMe)₂]Cl₂ were prepared from [PtCl₂(Bu ^t CN)₂]. Treatment of either [PtCl₂(dpmMe)] with PhC523-02CLi or [Pt(dpmMe)₂]Cl₂ with MeONa gave [Pt(Ph₂PCMe· PPh₂)₂]. Reaction of [PtCl₂(Bu ^t CN)₂] with [Pt(PPh₃)₄] and dpmMe gave a mixture of [Pt₂Cl₂(-dpmMe)₂] and [PtCl₂(dpmMe)]. The heterobimetallic complexes [Pt(C523-03CPh)₂ (-dpmMe)₂MX] (MX = HgCl₂ or AgCl) were made from the reaction of [Pt(dpmMe)₂]Cl₂ with Hg(C523-04CPh)₂ or Ag(C523-05CPh), respectively. Reaction of the Pt-Hg complex with Na₂S gave [Pt(C523-06CPh)₂ ( ¹-dpmMe)₂]. Oxidative addition of MeI to [PtMe₂· (dpmMe)] gave two Pt^IV isomers of the formula [PtMe₃I(dpmMe)].     

Synthesis of organo-platinum(II) and -palladium(II) complexes ofN-phenyl- andN-(p-Tolyl)pyrazole

Summary When platinum(II) chloride dissolved in acetic acid containing concentrated hydrochloric acid was refluxed withN-phenylpyrazole(liphpz) andN-(p-tolyl)pyrazole (Htlpz), complexes of composition [Pt(N-C)Cl]₂ (N-C = phpz, tlpz) were obtained, in which phpz and tlpz are coordinated through nitrogen and carbon forming a five membered metallocycle. Similar palladium(II) complexes [Pd(N-C)Cl]₂ were easily prepared by the reaction of palladium(II) chloride with Hphpz and Htlpz in methanol in the presence of lithium chloride. These [M(N-C)CI]₂ complexes reacted with tri-n-butylphosphine (PBu₃) and pyridine (py) to give the adducts [M(N-C)ClL](L = PBu₃, py). Ethylenediamine(en) and acetylacetone(Hacac) gave IPd(phpz)(en)]Cl and [Pd(phpz)(acac)] respectively. These new complexes are characterized by means of¹H-n.m.r. and i.r. spectra, and probable structures are proposed.Reprints of this article are not available.     

Trichloro(Dinitrogen)Platinate(II)

Zeise's salt, [PtCl₃(H₂C=CH₂)]⁻_, is the oldest known organometallic complex, featuring ethylene strongly bound to a platinum salt. Many derivatives are known, but none involving dinitrogen, and indeed dinitrogen complexes are unknown for both platinum and palladium. Electrospray ionization mass spectrometry of K₂[PtCl₄] solutions generate strong ions corresponding to [PtCl₃(N₂)]⁻, the identity of which was confirmed through ion-mobility spectrometry and MS/MS experiments that proved it to be distinct from its isobaric counterparts [PtCl₃(C₂H₄)]⁻ and [PtCl₃(CO)]⁻. Computational analysis established a gas-phase platinum–dinitrogen bond strength of 116 kJ mol⁻¹, substantially weaker than the ethylene and carbon monoxide analogues but stronger than for polar solvents such as water, methanol and dimethylformamide, and strong enough that the calculated N−N bond length of 1.119 Å represents weakening to a degree typical of isolated dinitrogen complexes.