Alberta Fontana

Organometallic complexes with biological molecules. XI. Solid state and in vivo investigations of some diorganotin(IV)-chloramphenicol and cycloserine derivatives

Abstract Diorganotin(IV) derivatives of chloramphenicol, {=D-(-)threo-2,2-dichloro-N-[ β -hydroxy- α -(hydroxymethyl)- β -(4-nitrophenyl)ethyl]acetamide (=Hchloramph)}, and D-cycloserine, {=(R)-4-amino-3-isoxazolidone [=Hcyclos]} have been prepared. The stoichiometries of the obtained compounds were R 2 SnClantib and R 2 Snantib 2 (antib −1 =chloramph −1 , R=methyl and phenyl; antib −1 =cyclos −1 , R=methyl). The solid state configuration of the complexes was investigated by I.R. and Mossbauer spectroscopy, from which structural hypotheses were inferred. In particular, the experimental data suggested monomer structures both for R 2 Sn(IV)Clchloramph and R 2 Sn(IV)chloramph 2 , in which chloramphenicolate anion behaved as monoanionic monodentate ligand through the oxygen atom of the deprotonated secondary alcoholic group, with formation of tetrahedral R 2 SnOCl and R 2 SnO 2 environments. In R 2 Sn(IV)Clcyclos and R 2 Sn(IV)cyclos 2 derivatives, Mossbauer spectroscopy, and in particular the narrowness of the full width at half height of the resonant peaks, Γ 1 and Γ 2 , suggested the occurrence of two different absorbing tin sites with different environments around the tin(IV) atoms. According to calculations performed by applying the point charge model formalism, one site was constituted by a tin(IV) tetrahedrically coordinated by monoanionic monodentate cycloserinate groups, through the oxygen atom of the resonance stabilised hydroxamate anion, originating R 2 SnClO and R 2 SnO 2 polyhedrons both in R 2 Sn(IV)Clcyclos and R 2 Sn(IV)cyclos 2 , respectively. The second site would correspond to a tin(IV) in a polymeric octahedral configuration with Me 2 SnCl 2 ON and Me 2 SnO 2 N 2 environments, in Me 2 Sn(IV)Clcyclos and Me 2 Sn(IV)cyclos 2 derivatives, respectively, in which the second donor atoms was the amino nitrogen atom. 1 H and 13 C NMR spectra, of both chloramphenicol and its diorganotin(IV) derivatives were carried in DMSO-d 6 solution, in which R 2 Sn(IV)Clchloramph and R 2 Sn(IV)chloramph 2 underwent total, (R=Me), or partial, (R=Ph), dissociation. As far as the organotin(IV)-D-cycloserine derivatives were concerned, 1 H and 13 C NMR spectra, also carried out for the free D-cycloserine, showed that, owing to the coordinating properties of the solvent, octahedral and trigonal bipyramidal isomers were present in DMSO solution of Me 2 Sn(IV)Clcyclos and Me 2 Sn(IV)cyclos 2 . Finally, the cytotoxic activity of the free chloramphenicol, D-cycloserine and of their dimethyltin(IV) derivatives has been investigated towards Ciona intestinalis and Ascidia malaca fertilised eggs, at different developing stages.

Nucleophilic attack by 2-pyridylpalladium(II) and platinum(II) complexes on the organic chlorides ClCH2R (R COMe, CN, Ph, Cl)

Abstract The 2-pyridyl complexes trans-[MCl(C5H4NC2)(PPh3)2] (M = Pd, 1a; M = Pt, 1b), [MCl(C5H4NC2)(dppe)] (M = Pd, 2a; M = Pt, 2b) and [M(dmtc)(C5H4NC2) (PPh3)] (M = Pd, 3a; M = Pt,3b) react with the chlorides ClCH2R(R  COMe, CN, Ph) to give cationic products containing the 2-pyridylium ligands (1-CH2R)C5H4NC2. The rate of nucleophilic displacement of the chloride ion from ClCH2R depends on the central metal (Pt > Pd), on the coordination geometry (1 ~ 3) and on the substituent R (COMe > CN > Ph for the reactions with 3b). Like 1b and 2b, complex 3b also reacts with dichloromethane to give [Pt(dmtc){(1-CH2Cl)C5H4NC2}(PPh3)]+. The reaction of the binuclear compound [{PdCl(μ-C5H4NC2,N)(PPh3)}2] with chloroacetone in the presence of chloride ion yields the zwitterionic derivative cis-[PdCl2{(1-CH2COMe)C5H4NC2}(PPh3)]. The cationic products have been isolated and characterized as perchlorate salts.

SCSA Code: Applications on the Cyclopeptide Renieramide

SCSA is an algorithm designed to get information on molecular conformational properties. The most stable conformers are determined by the homemade SCSA code, performing a multistep systematic conformational search, which involves energy and structure quantum chemical optimizations at low-level and high-level. The SCSA method was employed to analyze the conformational space of the in vacuo cyclopeptide renieramide at AM1 and B3LYP/6-31G(d) levels. Calculations at B3LYP level of the GIAO (13)C NMR chemical shifts were also performed on the final conformers. In fact, to validate the conformational search results experimental and calculated (13)C NMR spectra of renieramide were compared. Slight disagreements observed between experimental and calculated spectra could be attributed to solute-solvent interactions, which were not taken into account in the algorithm proposed here.

Organometallic nucleophiles. A mechanistic study of halide displacement at saturated carbon by 2- and 4-pyridyl complexes of palladium(II) and platinum(II)

Abstract The reactions of the 2- and 4-pyridyl complexes [MX(C 5 H 4 N C n )(dppe)] and trans -[MX(C 5 H 4 N C n )(PPh 3 ) 2 ] (M  Pd, Pt; X  Cl, Br; n = 2, 4)- involving halide displacement from the organic halides XCH 2 R (X  Cl, Br; R  CN, Ph, CH  CH 2 ) by the pyridyl nitrogen have been studied kinetically by conductivity in acetone or acetonitrile at 25°C. The kinetic data fit the second-order rate law rate k 2 [XCH 2 R][complex], in agreement with an S N 2 process at saturated carbon. The higher rates are displayed by the 2-pyridylplatinum derivatives with X  Br in both the metal complex and the organic halide. The higher nucleophilic power of the 2-pyridyl complexes compared with their 4-pyridyl analogs is paralleled by a higher basicity, as reflected by a higher p K a value. In any case, the metal-containing substituent enhances considerably the reactivity and basicity of the pyridine nitrogen. The rates are scarcely influenced by the coordination geometry around the metal.

Mechanism of oxidative allyl transfer from allylic ammonium cations to palladium(0) α-diimine complexes

Abstract The palladium(0) complex [Pd(η2-fn)(NN′)] (1, fn = fumaronitrile; NN′ = C5H4N-2-CH=NC6H4OME-4) reacts slowly and reversibly with A +  CH 2  CH=CH 2 (2a, A = NEt 3 ; 2 b , A = C 5 H 5 N ) to yield the cationic η3-allypalladium(II) derivative [ Pd (η[ 3 - C 3 H 5 )( N  N ′)] + (3) the free amine A and fn. The equilibrium constant Ke is (2.6 ± 0.1) × 10−3 for 2a and 1.0 ± 0.4 for 2b. Kinetic studies of these oxidative allyl-transfer reactions show that the rates increase with increasing concentration of 2 and with decreasing concentration of fn. A stepwise mechanism is proposed which involves slow and reversible displacement of fn by 2 to give a labile intermediate [ Pd (η 2 - CH 2 = CH  CH 2  A + ( N  N ′)] . This undergoes slow and reversible intramolecular allyl transfer through nucleophilic attack by the palladium(0) metal centre on the nitrogen-bound allyl carbon. The kinetic parameters evaluated by a steady-state treatment satisfactorily generate the observed equilibrium constant Ke. The rate of formation of the intermediate and the relative rate of its decay to the starting reactants and final products are virtually independent of the nature of the amine A.

Stereo and regioselectivity in the phenylation of cationic allylpalladium(II) α-diimine complexes by tetraphenylborate anion

The reaction of the cationic complex [Pd(4-methoxy-1,3-η3-cyclohexenyl)(py-2-CHNC6H4OMe-4)]+ (1) with BPh4− in the presence of fumaronitrile yields trans-3-methoxy-6-phenylcyclohexene (2a) and trans-4-methoxy-3-phenylcyclohexene (2b), in ca. 1 : 1 molar ratio. The trans stereochemistry of these products implies that the phenylation of the allyl ligand involves prior transfer of a phenyl group from BPh4− to the metal, followed by reductive coupling of the organic moieties. In the reactions of [Pd(η3-1,1-R1,R2-C3H3)(NN′)]+ (3) [NN′ 4-MeOH4C6NCHCHNC6H4OMe-4; py-2-CHNR (R  C6H4OMe-4, Me, or CMe3), 2,2′-bipyridine (bipy); R1  H, R2  Ph, Me; R1  R2  Me; with BPh4− in the presence of activated olefins, both regioisomers PhCH2CHCR1R2 (4a) and CH2CHCR1R2Ph (4b) are formed with a relative ratio which depends essentially on the allylic substituents: R1  H, R2  Ph, 4a > 98%; R1  H, R2  Me, 4a 75–67%; R1  R2  Me, 4a 64–58%. The regioisomer distribution is very little affected by the nature of the α-diimine, of the activated olefin, and of the solvent. For R1  H and R2  Ph, Me, the olefinic product 4a has a trans (E) geometry. These results have been interpreted in terms of reductive elimination occurring in the intermediate [PdPh(η3-1,1-R1,R2C3H3)(NN′)] with a σ-N monodentate α-diimine ligand.

Synthesis and chemico-physical characterization of tin(IV) complexes with some crown ethers

Abstract Some neutral adducts of diorganotin(IV) perchlorates and thiocyanates with three crown-ethers have been synthesised; they are of the type Me 2 SnX 2 L m · n H 2 O where m = 1 or 2, n = 2 or 4, X = ClO 4 or NCS, and L = 18-crown-6, 15-crown-5, and 12-crown-4. The values for m and n have been correlated with the coordinating ability of the two anions and with the steric hindrance by the crown ether molecules. From infrared and Mossbauer data, an octahedral coordination geometry is proposed for all the complexes. The Mossbauer parameters are discussed in terms of the electronegativity of the ligands on the tin(IV) center and of the distortions produced in the coordination polyhedra by the various crown-ether molecules. Preliminary DTG results suggest that it may be possible to obtain anhydrous complexes.

Cadmium(II) complexes of cytosine

SummaryComplexes of cadmium(II) with cytosine obtained from aqueous or physiological solutions at room temperature are reported. The complexes were characterized by spectroscopic, conductometric,1H-NMR, and13C-NMR measurements and also by thermogravimetry.ZusammenfassungEs wird über Komplexe von Cadmium(II) mit Cytosin berichtet, die aus wäßrigen oder physiologischen Lösungen erhalten wurden. Die Komplexe wurden mittels spektroskopischer Methoden, Konduktometrie,1H- und13C-NMR-Messungen und mittels Thermogravimetrie charakterisiert.

On coordination modes of adenine in cadmium(II) complexes

Complexes of cadmium(II) derivatives with adenine from water or by simulation of physiological conditions are obtained. The complexes have been studied by spectroscopic, conductometric, 1H-NMR, and by TG and DSC measurements. Possible coordination modes of the ligand are proposed.

Nucleophilic attack at co-ordinated isocyanides promoted by the 2-pyridyl ligand

The co-ordinated isocyanide in the 2-pyridyl intermediate [Pt(CNR)(C5H4N-C2)(dppe)]+[R = C6H4-OMe-4, dppe = 1,2-bis(diphenylphosphino)ethane] is readily attacked by protic nucleophiles, such as water, alcohols and primary amines. It is hydrolysed to CO and RNH2 by trace amounts of water in commercial benzene or acetone, and also reacts with the small amount of ethanol, present as a stabilizer in commercial chloroform, to yield the (ethoxy)aminocarbene complex [Pt{C(OEt)NHR}(C5H4N-C2)(dppe)]+. The reaction with p-anisidine (RNH2) is remarkably fast and gives the diaminocarbene complex [Pt{C(NHR)2}(C5H4N-C2)(dppe)]+. Similar but slower reactions with H2O and RNH2 occur for the 2-pyrazyl derivative [Pt(CNR)(C4H3N2-C2)(dppe)]+. The cationic complex [Pt(CNR)(C5H4NMe-C2)(dppe)]2+(C5H4NMe-C2= 1 -methyl-2-pyridylium) also reacts with RNH2 to form [Pt{C(NHR)2}(C5H4NMe-C2)(dppe)]2+, but at significantly lower rates. The enhanced reactivity of the isocyanide ligand in [Pt(CNR)(C5H4N-C2)(dppe)]+ is ascribed to the highly basic 2-pyridyl group in cis position, which assists the nucleophilic attack at the isocyanide carbon by hydrogen bonding with the incoming protic nucleophile. The complex cations [Pt{C(NHR)2}(C5H4N-C2)(dppe)]+ and [Pt{C(OEt)(NHR)}(C5H4N-C2)(dppe)]+ are better characterized through their ZnCI2 adducts, upon deprotonation of the carbene ligand with NEt3. The crystal and molecular structure of the binuclear complex [(dppe)Pt{C(NHR)NR}(C5H4N-C2)ZnCl2] has been determined by an X-ray analysis. This compound crystallizes in the orthorhombic system: space group Pna21, with a= 24.206(3), b= 14.269(3), c= 1 2.875(3)A and Z= 4. A total of 3265 reflections have been used in the refinement, resulting in a final R value of 0.029 and R′ of 0.027. The structure is characterized by a six-membered ring of boat conformation, formed by the platinum and zinc metal centres and the bridging carbon and nitrogen atoms of the 2-pyridyl and amidino ligands. A distorted square geometry is present around the platinum centre, with bond distances in the normal ranges: Pt–P 2.305(3) and 2.297(3)A, Pt–C(2-pyridyl) 2.044(10) and Pt–C(amidino) 2.035(8)A. Some distortion from tetrahedral geometry is present also around the zinc centre. The Zn ⋯ Pt distance of 3.238(1)A appears too long for any metal–metal bonding interaction.