Benzylamidine complexes of platinum(II) derived by nucleophilic addition of primary and secondary amines. X-ray crystal structure of trans-[PtCl2{Z-N(H)C(NHMe)CH2Ph}2]

The reaction of cis- and trans-[PtCl₂(NCCH₂Ph)₂] with a 5-fold excess of MeNH₂ and Me₂NH in CH₂Cl₂ at −10 °C affords in high yield the bis-amidine derivatives cis- and trans-[PtCl₂{Z-N(H)C(NHMe)CH₂Ph}₂] (1a, 2a) and cis- and trans-[PtCl₂{E-N(H)C(NMe₂)CH₂Ph}₂] (3a, 4a), respectively. The complexes were characterized by means of elemental analysis, multinuclear NMR and FT-IR techniques. The X-ray diffraction analysis was carried out for trans-[PtCl₂{Z-N(H)C(NHMe)CH₂Ph}₂] (2a).Moreover, the in vitro cytotoxicity for the new derivatives was evaluated in a wide panel of human tumor cell lines.     

Lanthanide iodides as promoters of acetonitrile amination. Molecular structure of MeC(NH)NHPr, MeC(NH)NHBu and {Dy[MeC(NH)NEt2]6}I3

Amination of acetonitrile by the amines MeNH₂, PrⁿNH₂, PrⁱNH₂, Bu^tNH₂, and Et₂NH is efficiently promoted by the lanthanide iodides LnI₂ (Ln = Nd, Dy, Tm), LnI₃ (Ln = Pr, Nd, Dy) and LnI₃(THF)₃ (Ln = Pr, Nd, Dy). The formed mono- and N,N′-disubstituted amidines MeC(NH)NHR (R = Prⁱ, Bu^t), MeC(NH)NEt₂, MeC(NR)NHR (R = Me, Prⁿ) were isolated mainly as the complexes with starting iodide of general composition LnI₂(amidine)_x (1) or LnI₃(amidine)_x (2) (x = 3-8). In the products 1, which evidently are the mixtures of LnI²⁺, and LnI₃ derivatives, the metal exists in trivalent state but one of the ligands actually is amidinate anion. A part of the generated amidines remains in the reaction solutions in free form. Heating of the 1 and 2 in vacuum at 150-200 °C affords corresponding amidine and the complexes with reduced amount of the amidine ligands LnI₂(amidine)_y (3) or LnI₃(amidine)_y (4) (y = 2-3). The products 3 and 4 displayed the same catalytic activity in the acetonitrile-amine cross-coupling as the initial iodides. SmI₂ and especially YbI₂ revealed lower activity. The structure of isopropylacetamidine (5), tert-butylacetamidine (6) and {Dy[MeC(NH)NEt₂]₆}I₃(MeCN) (7) were determined by X-ray diffraction analysis.     

Synthesis and structures of platinum(II) complexes with 5-ferrocenylpyrimidine

Reaction of platinum(II) salts with 5-ferrocenylpyrimidine (FcPM) afforded cis-[Pt(NH₃)₂(FcPM)₂](PF₆)₂ (1), trans-[Pt(NH₃)₂(FcPM)₂](PF₆)₂ (2), cis-[PtCl₂(FcPM)₂] (3), and cis-[PtCl₂(DMSO)(FcPM)] (4): their spectroscopic and electrochemical properties were investigated. Complexes 1 and 2 were structurally characterized by X-ray crystallography.     

cis-Dichloroplatinum (II) complexes with aminomethylnicotinate and -isonicotinate ligands

6-Aminomethylnicotinic acid (1a) and 2-aminomethylisonicotinic acid (1b) were each reacted with K₂PtCl₄ in aqueous 1 M HCl to give the corresponding N,N-chelated cis-dichloroplatinum(II) complexes 2. These were converted into amides 3 via their mixed anhydrides by treating them first with ethyl chloroformate and then with the respective 1° or 2° amine. The analogous 6-aminomethylnicotinic acid ester complexes 7 were obtained by reaction of the preformed ligands with K₂PtCl₄.     

Hydrogen bonding patterns in pyrazole Pt(II- and IV) chloride complexes

The solid-state packing arrays of the platinum(II) trans- and cis-[PtCl₂(PzH)₂] (1 and 2) and platinum(IV) trans- and cis-[PtCl₄(PzH)₂] (3 and 4) complexes have been examined and the occurrence of N-H ? Cl hydrogen-bonding associations in those structures has been discussed. Although different packing motifs are observed, in all cases molecules are interacting mostly via NH ? Cl and CH ? Cl associations. The square planar 1 and 2 form stacked arrays of PtCl₂(PzH)₂, which are supported by NH ? Cl and CH ? Cl hydrogen bonding. The isomeric structure of the complexes and orientation of the PzH rings determine NH ? Cl bonding mode (intermolecular or intramolecular) and also the extent of the platinum-platinum interaction. The synthetic procedures for the preparation of 1-4 along with elemental and X-ray analyses, TG/DTA, FAB⁺-MS, IR, and ¹H and ¹³C{¹H} NMR data are also given in this article.     

Platinum(II) and palladium(II) complexes with (N,N') and (C,N,N')- ligands derived from pyrazole as anticancer and antimalarial agents: synthesis, characterization and in vitro activities

The study of the reactivity of three 1-(2-dimethylaminoethyl)-1H-pyrazole derivatives of general formula [1-(CH₂)₂NMe₂}-3,5-R₂-pzol] {where pzol represents pyrazole and RH (1a), Me (1b) or Ph (1c)} with [MCl₂(DMSO)₂] (MPt or Pd) under different experimental conditions allowed us to isolate and characterize cis-[M{κ²-N,N′-{[1-(CH₂)₂NMe₂}-3,5-R₂-pzol])}Cl₂] {MMPtPt (2a-2c) or Pd (3a-3c)} and two cyclometallated complexes [M{κ³-C,N,N′-{[1-(CH₂)₂NMe₂}-3-(C₅H₄)-5-Ph-pzol])}Cl] {MPt(II) (4c) or Pd(II) (5c)}. Compounds 4c and 5c arise from the orthometallation of the 3-phenyl ring of ligand 1c. Complex 2a has been further characterized by X-ray crystallography. Ligands and complexes were evaluated for their in vitro antimalarial against Plasmodium falciparum and cytotoxic activities against lung (A549) and breast (MDA MB231 and MCF7) cancer cellular lines. Complexes 2a-2c and 5c exhibited only moderate antimalarial activities against two P. falciparum strains (3D7 and W2). Interestingly, cytotoxicity assays revealed that the platinacycle 4c exhibits a higher toxicity than cisplatin in the three human cell lines and that the complex 2a presents a remarkable cytotoxicity and selectivity in lung (IC₅₀ = 3 μM) versus breast cancer cell lines (IC₅₀ > 20 μM). Thus, complexes 2c and 4c appear to be promising leads, creating a novel family of anticancer agents. Electrophoretic DNA migration studies in presence of the synthesized compounds have been performed, in order to get further insights into their mechanism of action.     

Chloro and acetato complexes of platinum(II) with functionalized thioethers

The chloro complexes [PtCl₂(RSR′)₂] (1-10) (RSR′ = MeSCH₂C(O)OMe, 1; MeSCH₂C(O)OEt, 2; MeSCH₂C(O)Omenthyl(−), 3; MeSCH₂CH₂C(O)OMe, 4; , 5; EtSCH₂C(O)Me, 6; MeSCH(Me)C(O)Me, 7; MeSPh, 8; MeS-o-C₆H₄Me, 9; and MeS-o-C₆H₄Et, 10) are obtained in high yield (63-90%) by reaction of [PtCl₂(PhCN)₂] with the proper thioether in 1/2 molar ratio, in anhydrous chloroform, at reflux under argon for ca. 10 h. The X-ray crystal structure of [PtCl₂(MeS-o-C₆H₄Me)₂] (9) shows an almost regular trans square planar geometry (triclinic, space group , a 6.806(1), b 7.789(2), c 10.085(3) Å, α 101.80(2)°, β 69.55(2)°, γ 115.27(2)°, R(F_o) 0.023, ). The dichloro complexes react with silver acetate in a complex manner, which depends on the nature of the thioether, and only with RSR′ = MeSPh the simple diacetato complex [Pt(OAc)₂(RSR′)₂] is obtained as the major product.     

The influence of substituents (R) at N atom of thiophene-2-carbaldehyde thiosemicarbazones {(C4H3S)HCN-N(H)-C(S)NHR} on bonding, nuclearity and H-bonded networks of copper(I) complexes

The nuclearity, bonding and H-bonded networks of copper(I) halide complexes with thiophene-2-carbaldehyde thiosemicarbazones {(C₄H₃S)HC²N³-N(H)-C¹(S)N¹HR} are influenced by R substituents at N¹ atom. Thiophene-2-carbaldehyde-N¹-methyl thiosemicarbazone (HttscMe) or thiophene-2-carbaldehyde-N¹-ethyl thiosemicarbazone (HttscEt) have yielded halogen-bridged dinuclear complexes, [Cu₂(μ-X)₂(η¹-S-Htsc)₂(Ph₃P)₂] (Htsc, X: HttscMe, I, 1; Br, 2; Cl, 3; HttscEt, I, 4; Br, 5; Cl, 6), while thiophene-2-carbaldehyde-N¹-phenyl thiosemicarbazone (HttscPh) has yielded mononuclear complexes, [CuX(η¹-S-HttscPh)₂] (X, I, 7a; Br 8; Cl, 9) and a sulfur bridged dinuclear complex, [Cu₂(μ-S-HttscPh)₂(η¹-S-HttscPh)₂I₂] 7b co-existing with 7a in the same unit cell. These results are in contrast to S-bridged dimers [Cu₂(μ-S-Httsc)₂(η¹-Br)₂(Ph₃P)₂] · 2H₂O and [Cu₂(μ-S-Httsc)₂(η¹-Cl)₂(Ph₃P)₂] · 2CH₃CN obtained for R = H and X = Cl, Br (Httsc = thiophene-2-carbaldehyde thiosemicarbazone) as reported earlier. The intermolecular CH_Ph?π interaction in 1-3 (2.797 Å, 1; 3.264 Å, 2; 3.257 Å, 3) have formed linear polymers, whereas the CH_Ph?X and N³?HCH interactions in 4-6 (2.791, 2.69 Å, 5; 2.776, 2.745 Å, 6, respectively) have led to the formation of H-bonded 2D polymer. The PhN¹H?π, interactions (2.547 Å, 8, 2.599 Å, 9) have formed H-bonded dimers only. The Cu?Cu separations are 3.221-3.404 Å (1-6).     

Synthesis, structures and in vitro cytotoxicity of some platinum(II) complexes containing thiocarbamate esters

The thiocarbamate esters 4-RC₆H₄NHC(S)OMe (R = H, Cl, OMe, NO₂, Me) react with cis-[PtCl₂(PTA)₂] (PTA = 1,3,5-triaza-7-phosphaadamantane) in the presence of base to afford the platinum(II) complexes trans-[Pt{SC(OMe)NC₆H₄R}₂(PTA)₂] (R = H, Cl, OMe, NO₂, Me) in high yields. The complexes were fully characterised spectroscopically and, in case of the NO₂ derivate, by X-ray crystallography. Cytotoxicity of these complexes was studied in vitro in four human cancer cell lines (CH1, HT29, A549, SK-OV-3) using the MTT assay. The results show that the Cl substituted derivate is the most potent of these compounds in vitro. Moreover, this derivative is capable of partially circumventing primary cisplatin resistance in ovarian and colon carcinoma cells.     

A fluorene-based diphosphinite ligand, its Ni, Pd, Pt, Fe, Co and Zn complexes and the first structurally characterized diphosphinate metal chelates

The diphosphinite ligand 9,9-(Ph₂POCH₂)₂-fluorene (1) was reacted with group 10 metal dichlorides to form chelate complexes of formula [MCl₂(1)] (MNi, 2; MPd, 3; MPt, 4) showing 8-membered metallocycles. Chloride abstraction from 3 with AgOTf afforded the dinuclear complex [M(μ-Cl)Pd(1)]₂(OTf)₂ (5), in which the ligand adopts a different conformation with respect of 3. In 5, the fluorene moiety and the phenyl groups display stabilizing interactions with the anion which is located close to the metal centre. With Fe(II), Co(II) and Zn(II) chlorides, the non-isolated intermediates [MCl₂(1)] readily undergo oxidation to [MCl₂(1_ox)] (MFe, 6; MCo, 7; MZn, 8; 1_ox = 9,9-(Ph₂P(O)OCH₂)₂-fluorene) in which the diphosphinate ligand and the metal centre form 10-membered metallocycles. Complexes 6-8 are the first examples of structurally characterized diphosphinate metal chelates. The Zn(II) diphosphinite complex [ZnCl₂(1)] (9) could be observed by NMR spectroscopy, along with the mixed phosphinite-phosphinate, mono-oxidized complex which is an intermediate in the formation of 8. Complex [ZnCl₂(9.9-fluorene-dimethanol)(Ph₂P(O)H)] (10) was also observed as hydrolysis product of 9. The X-ray molecular structures of 2, 3, 5.2OTf, 6, 7, 8 and 10 are reported.     

Platinum(II) halide complexes of PPh2(CFCF2) and PPh2(CClCF2). The synthesis and crystal structure of [PtI(μ-I){PPh2(CXCF2)}]2, (X = F, Cl); the first crystallographically characterised iodide-bridged platinum(II) phosphine dimers

The reactions of the fluorovinyl-substituted phosphines PPh₂(CFCF₂) and PPh₂(CClCF₂), with K₂PtX₄ (X = Br, I) have been investigated. The resulting complexes have been characterized by a combination of ¹⁹F and ³¹P{¹H} NMR, IR and Raman spectroscopy. The reactions of these phosphines with K₂PtBr₄ yield the monomeric complexes cis-[PtBr₂{PPh₂(CFCF₂)}₂] (1) and trans-[PtBr₂{PPh₂(CClCF₂)}₂] (2), respectively, whilst the reactions with K₂PtI₄ yield both the monomeric species trans-[PtI₂{PPh₂(CXCF₂)}₂], {X = F (3), Cl (4)}, and the dimeric species [PtI(μ-I){PPh₂(CXCF₂)}]₂, {X = F (5), Cl (6)}. The dimers 5 and 6 represent the first crystallographically characterised platinum(II) iodide-bridged phosphine complexes, and both adopt the symmetric-trans structure.     

Synthesis, X-ray crystal structures and properties of complex salts and sterically crowded heteroleptic complexes of group 10 metal ions with aromatic sulfonyl dithiocarbimates and triphenylphosphine ligand

Two new complex salts of the form (Bu₄N)₂[Ni(L)₂] (1) and (Ph₄P)₂[Ni(L)₂] (2) and four heteroleptic complexes cis-M(PPh₃)₂(L) [M = Ni(II) (3), Pd(II) (4), L = 4-CH₃OC₆H₄SO₂NCS₂] and cis-M(PPh₃)₂(L′) [ M = Pd(II) (5), Pt(II) (6), L′ = C₆H₅SO₂NCS₂] were prepared and characterized by elemental analyses, IR, ¹H, ¹³C and ³¹P NMR and UV-Vis spectra, solution and solid phase conductivity measurements and X-ray crystallography. A minor product trans-Pd(PPh₃)₂(SH)₂, 4a was also obtained with the synthesis of 4. The NiS₄ and MP₂S₂ core in the complex salts and heteroleptic complexes are in the distorted square-plane whereas in the trans complex, 4a the centrosymmetric PdS₂P₂ core is perforce square planar. X-ray crystallography revealed the proximity of the ortho phenyl proton of the PPh₃ ligand to Pd(II) showing rare intramolecular C-H?Pd anagostic binding interactions in the palladium cis-5 and trans-4a complexes. The complex salts with σ_rt values ∼10⁻⁵ S cm⁻¹ show semi-conductor behaviors. The palladium and platinum complexes show photoluminescence properties in solution at room temperature.     

Synthesis of amidate-hanging platinum mononuclear complexes by base hydrolysis of nitrile complexes

The “amidate-hanging” Pt mononuclear complexes, which can easily bind a second metal ion with the non-coordinated oxygen atoms in the amidate moieties, have been synthesized and characterized by ¹H NMR, MS, IR spectroscopy, and single crystal X-ray analysis. Five new complexes with various amidate ligands and co-ligands, cis-[Pt(PVM)₂(en)] · 4H₂O (1, PVM = pivaloamidate, en = ethylenediamine), cis-[Pt(PVM)₂(NH₂CH₃)₂] · H₂O (2), cis-[Pt(PVM)₂(NH₂^tBu)₂] (3), cis-[Pt(TCM)₂(NH₃)₂] (4, TCM = trichloroacetamidate), and cis-[Pt(BZM)₂(NH₃)₂] (5, BZM = benzamidate), were successfully synthesized by direct base hydrolysis of the corresponding Pt nitrile complexes, cis-[Pt(NCR)₂(Am)₂]²⁺ (P1, P2, P3, and P5) (NCR = nitrile, Am = amine). These nitrile complexes were obtained by introducing nitriles into the Pt aqua complexes, cis-[Pt(OH₂)₂(Am)₂](ClO₄)₂, whereas introduction of trichloronitrile into [Pt(OH₂)₂(NH₃)₂](ClO₄)₂ induced more facilitated water nucleophilic attack to afford [Pt(TCM)(NH(COH)CCl₃)(NH₃)₂](ClO₄) (P4). The base treatments of the precursor complexes (P1-5) lead to produce “amidate-hanging” Pt mononuclear complexes (1-5) without geometry isomerization. The ¹⁹⁵Pt chemical shifts for 1-5 exhibit subtle differences of the Pt electron densities among them.     

Synthesis of new platinum(II) compounds with several bidentate and tridentate nitrogen-donor ligands. Structural analyses by H, C{H} and Pt{H} NMR spectroscopy and X-ray crystal structure

The reaction of the N-alkylaminopyrazole (NN′) ligands 1-[2-(ethylamino)ethyl]-3,5-dimethylpyrazole (deae), 1-[2-(tert-butylamino)ethyl]-3,5-dimethylpyrazole (deat), or (NN′N) ligands bis[(3,5-dimethylpyrazolyl)methyl]ethylamine (bdmae) and bis[(3,5-dimethylpyrazolyl)ethyl]ethylamine (ddae) with [PtCl₂(CH₃CN)₂] affords a series of square-planar Pt(II) complexes with formula [PtCl₂(NN′)] (NN′ = deae (1); deat (2)), [PtCl₂(bdmae)] (3), or [PtCl(ddae)]Cl (4). Treatment of complex 4 in the presence of AgBF₄ in CH₂Cl₂/methanol (3:1) gives [PtCl(ddae)](BF₄) (5). These Pt(II) complexes have been characterised by elemental analyses, conductivity measurements and IR, ¹H, ¹³C{¹H}, and ¹⁹⁵Pt{¹H} NMR spectroscopies. The ¹H NMR spectroscopic studies of the complexes prove the rigid conformation of the ligands when they are complexed. The solid-state structure of complex 1 was determined by single crystal X-ray diffraction methods. The deae ligand is coordinated through the N_pz and N_amino atoms to the metallic centre, which completes its coordination with two chlorine atoms in cis disposition.     

The first metal complexes bearing ligated 3-iminoisoindolin-1-ones

The reaction between Zn(OAc)₂ · 2H₂O (1) and the 3-iminoisoindolin-1-ones H₂NCNC(O)C₆R¹R²R³R⁴ (R¹-R⁴ = H 2; R¹, R⁴ = H, R², R³ = Cl 3; R¹, R³, R⁴ = H, R² = Me 4) in EtCN at 70 °C for ca. 12 h affords the novel family of complexes [Zn{H₂NCNC(O)C₆R¹R²R³R⁴}₂(OAc)₂] (R¹-R⁴ = H 5; R¹, R⁴ = H, R², R³ = Cl 6; R¹, R³, R⁴ = H, R² = Me 7) in excellent (90% and 93% for 5 and 6, correspondingly) to good (64% for 7) yields. The isolated compounds were characterized by elemental analyses (C, H, N), IR, NMR and ESI⁺-MS. X-ray diffraction data for 2 and 5 indicate that both free (2) and ligated (5) 3-iminoisoindolin-1-ones exist in the zwitterionic form.     

Synthesis and reactivity with amines of new diiron alkynyl methoxy carbene complexes

The new diiron alkynyl methoxy carbene complexes [Fe₂{μ-CN(Me)(R)}(μ-CO)(CO){C(OMe)CCR′}(Cp)₂]⁺ (R = 2,6-Me₂C₆H₃ (Xyl), R′ = Tol, 3a; R = Xyl, R′ = Ph, 3b; R = Xyl, R′=Buⁿ, 3c; R = Xyl, R′=SiMe₃, 3d; R = Me, R′ = Tol, 3e; R = Me, R′ = Ph, 3f) are obtained in two steps by addition of R′CCLi (R′ = Tol, Ph, Buⁿ, SiMe₃) to the carbonyl aminocarbyne complexes [Fe₂{μ-CN(Me)(R)}(μ-CO)(CO)₂(Cp)₂]⁺ (R = Xyl, 1a; Me, 1b), followed by methylation of the resulting alkynyl acyl compounds [Fe₂{μ-CN(Me)(R)}(μ-CO)(CO){C(O)CCR′}(Cp)₂] (R = Xyl, R′ = Tol, 2a; R = Xyl, R′ = Ph, 2b; R = Xyl, R′ = Buⁿ, 2c; R = Xyl, R′ = SiMe₃, 2d; R = Me, R′ = Tol, 2e; R = Me, R′ = Ph, 2f). Complexes 3 react with secondary amines (i.e., Me₂NH, C₅H₁₀NH) to give the 4-amino-1-metalla-1,3-dienes [Fe₂{μ-CN(Me)(R)}(μ-CO)(CO){C(OMe)CHC(R′)(NMe₂)}(Cp)₂]⁺ (R = Xyl, R′ = Tol, 4a; R = Xyl, R′ = Ph, 4b; R = Me, R′ = Ph, 4c) and [Fe₂{μ-CN(Me)(Xyl)}(μ-CO)(CO){C(OMe)CHC(Tol)(NC₅H₁₀)}(Cp)₂]⁺, 5. The addition occurs stereo-selectively affording only the E-configured products. Analogously, addition of primary amines R′NH₂ (R′ = Ph, Et, Prⁱ) affords the 4-(NH-amino)-1-metalla-1,3-diene complexes [Fe₂{μ-CN(Me)(Xyl)}(μ-CO)(CO){C(OMe)CHC(R)(NHR′)}(Cp)₂]⁺ (R = Ph, 6a; Et, 6b; Prⁱ, 6c). In the case of 6a, only the E isomer is formed, whereas a mixture of the E and Z isomers is present in the case of 6b,c, with prevalence of the latter. Moreover, the two isomeric forms exist under dynamic equilibrium conditions, as shown by VT NMR studies. Complexes 6 are deprotonated by strong bases (e.g., NaH) resulting in the formation of the neutral vinyl imine complexes [Fe₂{μ-CN(Me)(Xyl)}(μ-CO)(CO){C(OMe)CHC(NR)(Tol)}(Cp)₂] (R = Ph, 7a; Et, 7b; Prⁱ, 7c); the reaction can be reverted by addition of strong acids. X-ray crystal structures have been determined for 3a[CF₃SO₃] · Et₂O, 4c[CF₃SO₃], 6a[BF₄] · CH₂Cl₂, 6c[CF₃SO₃] · 0.5Et₂O and 7a · CH₂Cl₂.     

Modification of aminoallenylidene complexes of chromium via exchange of the C3-bound amino group

The aminoallenylidene(pentacarbonyl)chromium complexes [(CO)₅CrCCC(NR¹R²)Ph] (1a-c) react with dimethylamine by addition of the amine to the C1C2 bond of the allenylidene ligand to give alkenyl(amino)carbene complexes [(CO)₅CrC(NMe₂)CHC(NR¹R²)Ph] (2a-c) (R¹ = Me: R² = Me (a), Ph (b); R¹ = Et: R² = Ph (c)). In contrast, addition of a large excess (usually 20 equivalents) of ammonia or primary amines, H₂NR, to solutions of [(CO)₅CrCCC(NMe₂)Ph] (1a) affords the aminoallenylidene complexes [(CO)₅CrCCC(NHR)Ph] (1d-w) in which the dimethylamino group is replaced by NH₂ or NHR, respectively. In addition to simple amines such as methylamine, butylamine, and aniline, amines carrying a functional group (allylamine, propargylamine) and amino acid esters as well as amino terpenes and amino sugars can be used to displace the NMe₂ substituent. Usually the Z isomer (with respect to the partial C3-N double bond) is formed exclusively. Products derived from addition of H₂NR to the C1C2 bond of 1a are not observed. The amino group in 1d-w is rapidly deprotonated by excess of amine to form iminium alkynyl chromates [1d-w]⁻, thus protecting 1d-w from addition of free amine to either C3 or across the C1C2 bond. The iminium alkynyl chromates are readily reprotonated by acids or by chromatography on wet SiO₂ to reform 1d-w.     

Fluorescent analogues of quinoline reveal amine ligand loss from cis and trans platinum(II) complexes in cancer cells

Analogues of cytotoxic cis and trans dichloridoplatinum(II) complexes with one ammonia and one aromatic amine (cis- and trans-[PtCl₂(aromatic amine)(NH₃)]) were synthesised in which the aromatic group was replaced by the fluorescent ligand 7-azaindole (1). Coordination resulted in almost complete quenching of the fluorescence and the ligand had a effect on the biological activities of the cis and trans isomers similar to that previously reported for aromatic amines as is exemplified by them having similar cytotoxicities (IC₅₀ 3.6(5) and 6.0(19) μM, respectively). Observation of fluorescence following treatment of the cis complex with cysteine, glutathione, or methionine suggests labilisation and subsequent loss of the putative non-leaving group ligands. No such effect was observed for the trans complex which does not experience trans labilisation. Two-photon excitation of cells that had been treated with the complexes gave rise to observable fluorescence, suggesting ligand displacement for both complexes. The fluorescence appears to be localised in the lysosomes or late endosomes. These complexes are excellent models of analogues of cytotoxic cis and trans complexes with aromatic amine ligands and can be used to study the metabolism of the non-leaving group positions.     

Pt(IV) complexes as prodrugs for cisplatin

The antitumor effects of platinum(IV) complexes, considered prodrugs for cisplatin, are believed to be due to biological reduction of Pt(IV) to Pt(II), with the reduction products binding to DNA and other cellular targets. In this work we used pBR322 DNA to capture the products of reduction of oxoplatin, c,t,c-[PtCl₂(OH)₂(NH₃)₂], 3, and a carboxylate-modified analog, c,t,c-[PtCl₂(OH)(O₂CCH₂CH₂CO₂H)(NH₃)₂], 4, by ascorbic acid (AsA) or glutathione (GSH). Since carbonate plays a significant role in the speciation of platinum complexes in solution, we also investigated the effects of carbonate on the reduction/DNA-binding process. In pH 7.4 buffer in the absence of carbonate, both 3 and 4 are reduced by AsA to cisplatin (confirmed using ¹⁹⁵Pt NMR), which binds to and unwinds closed circular DNA in a manner consistent with the formation of the well-known 1, 2 intrastrand DNA crosslink. However, when GSH is used as the reducing agent for 3 and 4, ¹⁹⁵Pt NMR shows that cisplatin is not produced in the reaction medium. Although the Pt(II) products bind to closed circular DNA, their effect on the mobility of Form I DNA is different from that produced by cisplatin. When physiological carbonate is present in the reduction medium, ¹³C NMR shows that Pt(II) carbonato complexes form which block or impede platinum binding to DNA. The results of the study vis-à-vis the ability of the Pt(IV) complexes to act as prodrugs for cisplatin are discussed.     

Reaction of [MCl2(CH3CN)2] (M = Pd(II), Pt(II)) compounds with N1-alkylpyridylpyrazole-derived ligands

Palladium(II) and platinum(II) complexes with N-alkylpyridylpyrazole-derived ligands, 2-(1-ethyl-5-phenyl-1H-pyrazol-3-yl)pyridine (L¹) and 2-(1-octyl-5-phenyl-1H-pyrazol-3-yl)pyridine (L²), cis-[MCl₂(L)] (M = Pd(II), Pt(II)), have been synthesised. Treatment of [PdCl₂(L)] (L = L¹, L²) with excess of ligand (L¹, L²), pyridine (py) or triphenylphosphine (PPh₃) in the presence of AgBF₄ and NaBPh₄ produced the following complexes: [Pd(L)₂](BPh₄)₂, [Pd(L)(py)₂](BPh₄)₂ and [Pd(L)(PPh₃)₂](BPh₄)₂. All complexes have been characterised by elemental analyses, conductivity, IR and NMR spectroscopies. The crystal structures of cis-[PdCl₂(L²)] (2) and cis-[PtCl₂(L¹)] (3) were determined by a single crystal X-ray diffraction method. In both complexes, the metal atom is coordinated by one pyrazole nitrogen, one pyridine nitrogen and two chlorine atoms in a distorted square-planar geometry. In complex 3, π-π stacking between pairs of molecules is observed.