M. Fátima M. Piedade

Inhibition of cancer cell growth by ruthenium(II) cyclopentadienyl derivative complexes with heteroaromatic ligands

Inhibition of the growth of LoVo human colon adenocarcinoma and MiaPaCa pancreatic cancer cell lines by two new organometallic ruthenium(II) complexes of general formula [Ru(eta(5)-C(5)H(5))(PP) L][CF(3)SO(3)], where PP is 1,2-bis(diphenylphosphino)ethane and L is 1,3,5-triazine (Tzn) 1 or PP is 2x triphenylphosphine and L is pyridazine (Pyd) 2 has been investigated. Crystal structures of compounds 1 and 2 were determined by X-ray diffraction studies. Atomic force microscopy (AFM) images suggest different mechanisms of interaction with the plasmid pBR322 DNA; while the mode of binding of compound 1 could be intercalation between base pairs of DNA, compound 2 might be involved in a covalent bond formation with N from the purine base.

Decavanadates: a building-block for supramolecular assemblies

Abstract A donor–acceptor intermolecular interaction survey was performed for compounds containing the [H n V 10 O 28 ] 6– n anion, based on a Cambridge Structural Database search and on X-ray data examples in recent literature. Our aim was to systematize the supramolecular motifs present in the solid-state structures in order to understand the key factors determining the crystal packing of decavanadates and to develop a base for a methodology to construct new arrays. We were able to find four different main motifs: monomers, dimers, 1D and 2D arrays that were systematically analysed. The supramolecular assemblies found seem to depend both in the degree and site of protonation of the decavanadates, as well as on the size and shape of solvent and cation molecules.

Polymorphic gabapentin: thermal behaviour, reactivity and interconversion of forms in solution and solid-state

The various crystal forms of the neuroleptic drug gabapentin have been investigated, and in some cases re-investigated, by a combination of differential scanning calorimetry, hot stage microscopy and variable temperature powder diffraction methods in order to establish the relative stability of both its anhydrous and hydrated forms. A series of steps involving slurrying, heating, de-hydration and reaction with vapours of HCl have been performed. In this latter case, it has been possible to show that the reaction with HCl vapour leads to the same product as that obtained in solution. In slurry experiments in the absence of water, the most stable form, Form II, is invariably obtained, whereas in water, the slurry leads to the conversion of all crystal forms to the hemihydrated Form I. The conditions for the solid-state formation of the gabapentin-lactam de-hydration product have been analysed. Co-crystal formation has also been attempted. In the course of one such experiment, 1 : 1 co-crystals of gabapentin-lactam and benzoic acid were obtained.

Second harmonic generation of η5-monocyclopentadienyl ruthenium p-benzonitrile derivatives by Kurtz powder technique. Crystal and molecular structure determinations of [Ru(η5-C5H5)((+)-DIOP)(p-NCC6H4NO2)][X], X=PF6−, CF3SO3− and [Ru(η5-C5H5)((+)-DIOP)(NCCH3)][PF6]

Abstract A new series of salts [RuCp(PP)( p -NC(CHCH) n C 6 H 4 R)][X] (PP=((+)-DIOP, DPPE; n =0, 1; R=CH 3 , Br, OCH 3 , NH 2 , N(CH 3 ) 2 , C 6 H 5 and NO 2 ; X=PF 6 − , CF 3 SO 3 − ) were synthesised and the second harmonic generation (SHG) efficiencies were measured by Kurtz powder technique in order to better understand the relationship between structural features and solid state packing with SHG properties. A structural study of [RuCp((+)-DIOP)( p -NCC 6 H 4 NO 2 )][X], X=PF 6 − , CF 3 SO 3 − by X-ray diffraction showed crystallisation on accentric groups. The PF 6 − salt crystallised in a triclinic space group P 1 showing perfect parallel alignment of the molecular dipoles. The CF 3 SO 3 − salt crystallised in a monoclinic space group P 2 1 and shows an angle of 73.8° between the molecular dipoles in the unit cell. Complex [RuCp((+)-DIOP)( p -NCCH 3 )][PF 6 ], studied for comparison, crystallises in the C 222 1 space group and shows eight molecules per unit cell randomly orientated. Comparison of the RuN and NC distances between the three compounds are in agreement with metal–nitrile bonding suggested by the spectroscopic data.

New forms of old drugs: improving without changing

In a short approach, we want to present the improvements that have recently been done in the world of new solid forms of known active pharmaceutical ingredients (APIs). The different strategies will be addressed, and successful examples will be given.

High first hyperpolarizability and perfectly aligned crystal packing for an organometallic compound [Fe(η5-C5H5)((R)–PROPHOS)(p-NCC6H4NO2)][PF6]·CH2Cl2

Abstract The molecular first hyperpolarizability, β, and the X-ray crystal structure of the complex [Fe(η5-C5H5)((R)–PROPHOS)(p-NCC6H4NO2)][PF6] ((R)–PROPHOS=(R)–(+)-bis-(1,2-diphenylphosphino)propane) were determined. A near-resonant enhanced β value as high as 545×10−30 esu was obtained from hyper-Rayleigh scattering measurements. In addition, the compound crystallizes in the space group P1 with a perfect alignment of the dipolar molecules (only a single chromophore per unit cell), thus maximizing the macroscopic nonlinearity for electro-optic or parametric frequency conversion applications. The molecular packing in the crystal is analyzed in order to understand the factors leading to the perfect alignment.

Revisiting paracetamol in a quest for new co-crystals

Paracetamol, one of the most widely available analgesics, is long known, but still a challenge for crystal engineers. Herein we discuss a new polymorphic form of the morpholine solvate and present two novel co-crystals with lone pair heterocycles.

Organometallic nickel(II) complexes with substituted benzonitrile ligands. Synthesis, electrochemical studies and non-linear optical properties. The X-ray crystal structure of [Ni(η5-C5H5){P(C6H5)3}(NCC6H4NH2)][PF6]

Abstract A new family of organometallic Ni(II) benzonitrile derivatives bearing strong donor substituents of general formula [Ni(η5-C5H5){P(C6H5)3}NCC6H4R][PF6] (R=NH2, N(CH3)2, C6H5, OCH3, H, F) has been synthesized. A structural study by X-ray diffraction of the compound with R=NH2 showed crystallization on the centrosymmetric monoclinic space group, P21/n, with a quasi planar structure of the coordinated nitrile. First and second hyperpolarizabilities evaluated by hyper-Rayleigh scattering and Maker fringe techniques showed essentially the same values for the complexes and the uncoordinated chromophores. Theoretical studies by the extended Huckel method found a small amount of π delocalization due to the cancelling effects on the interaction of the metal fragment orbitals with π and π* nitrile orbitals.

Synthesis of new donor/acceptor η5-cyclopentadienyl and η5-indenyliron(II) complexes with p-benzonitrile derivatives. Crystal structures of [Fe(η5-C5H5)(CO)(P(OC6H5)3)(p-NCC6H4NO2)][BF4]·CH2Cl2 and [Fe(η5-C9H7)(CO)(P(OC6H5)3)(p-NCC6H4NO2)][BF4]

Abstract New complexes of the type [Fe(η5-Cp or Ind)(L)(L′)(p-NCR)][BF4] (L, L′=CO, P(OC6H5)3, P(C6H5)3; R=C6H4N(CH3)2, C6H4NO2, (E)-C(H)C(H)C6H4NO2, (E)-C(H)C(H)C6H4N(CH3)2) have been synthesised and characterised. Spectroscopic data were analysed in order to evaluate the tuning of the electronic density at the metal centre and the extension of the π-delocalisation on the molecule, due to the presence of coligands with different acceptor/donor abilities. The structures of two complexes [Fe(η5-C5H5)(CO)(P(OC6H5)3)(p-NCC6H4NO2)][BF4] and [Fe(η5-C9H7)(CO)(P(OC6H5)3)(p-NCC6H4NO2)][BF4] were determined by X-ray crystallographic analysis. The compounds crystallised in the centrosymmetric space groups P1 and P21/n, respectively. Bond distances within the nitrile ligand are discussed in order to evaluate the nature of iron–nitrile bonding in these complexes.

Studies on molybdenocene derivatives: Reactions of [Cp2Mo(η2-NCMe)] and preparation of alkyl hydride complexes. Crystal structure of [Cp2Mo(PMe3)]

Abstract Reaction of [Cp 2 Mo(η 2 -NCMe)] ( 1 ) with PMe 3 affords [CP 2 Mo(PMe 3 )] ( 2 ), which is readily alkylated go give [Cp 2 MoR(PMe 3 )]PF 6 ( 3a , R = Me; 3b , R = Et). The crystal structure of 2 shows tricoordination around the Mo atom. Cyclic voltammetry of 3a and 3b and the analogues [Cp 2 MoR(CNMe)]I, ( 4a , R = Me; 4b , R = Et) and [Cp 2 MoMe(PPh 3 )]PF 6 ( 7 ) shows one reversible one-electron oxidation, but the potential is independent of R, in contrast to the complexes [Cp 2 MoR 2 ]. Oxidative addition of Et 2 S 2 , Ph 2 Se 2 or (PhCOO) 2 to 1 yields [Cp 2 Mo(ER) 2 ] (E = O, S or Se). The molybdenocene alkyl hydrides [Cp 2 Mo(H)Me] ( 5 ) and [Cp 2 MoH(CH 2 PPh 3 )]I·THF ( 6 ) are prepared from [Cp 2 MoHI]. Thermal decomposition of 6 as well as reaction Of [Cp 2 MoMe 2 ] + with Ph 3 C . provide evidence for transient formation of the methylidene complex [Cp 2 MoH(CH 2 )] + .