R.M.G. Roberts

Studies on the anti-tumour activity of some iron sandwich compounds

Abstract Four types of water-soluble iron sandwich compounds, ferrocenes bearing charged side chains (Ia), ferrocenium salts (Ib), (η-arene) 2 Fe 2+ salts (II) and (η-cyclopentadienyl)Fe + salts (III), have been tested in in vitro against experimental tumours, L1210, Walkers and Chinese hamster lung (V.79). Some activity was observed for all the types of complex; though that of only two, Ib and II, was good. Of special interest is that the iron(II) sandwich type II compounds display anti-tumour activity, since previous active complexes have contained type Ib or other known cytotoxic groups that would account for their activity. Examples of complexes of type Ib and II were further tested against improved cell lines L1210, PC6 and CHl. The results show the two types to be similar in their effect and specificity. An attempt is made to rationalise the data.

Mössbauer studies on ferrocene complexes IX. Phosphaferrocenes and their protonated derivatives

Abstract A number of mono- and di-phosphaterrocenes have been synthesised and their NMR (1H, 31P) and Mossbauer spectra measured. The presence of a phosphorus atom in the cyclopentadienyl (Cp) moiety causes a reduction of about 0.3 mm s−1 in the quadrupole splitting (QS) compared with what of ferrocene. The effect appears to be additive, as does the effect of Cp ring substituents. Thus 2,5-diphenylphosphaferrocene (I), 3,3′,4,4′-tetramethyldiphosphaferrocene (II) and 2,2′,5,5′-tetraphenyldiphosphaferrocene (III) have QS values of 2.03, 1.82 and 1.52 mm s−1, respectively. III dissolves readily and reversibly in triflic acid (CF3SO3H) to give a phenyl ring protonated species. The Mossbauer spectrum of the frozen solution shows a significant increase in QS to 1.77 mm s−1 which is interpreted in terms of iron participation in the stabilisation of the σ complex. H/D exchange reactions and oxidation of phosphaferrocenes are briefly reported together with an improved synthesis of the important precursor, 1,2,5-triphenylphosphole.

Mössbauer studies on ferrocene complexes: XII. Relationships between oxidation potentials and quadrupole splittings☆

Abstract A linear relationship was found between oxidation potentials (measured chronopotentiometrically as quarter-wave potentials E ° 1 4 (V)) and 57 Fe Mossbauer quadrupole splittings ( QS mm s −1 ) for a series of mono- and di-substituted ferrocenes. This relationship is discussed in terms of molecular orbital energy levels in ferrocenes particularly in respect of the variation of both E ° 1 4 and QS with Hammett substituent parameters.

Evidence of ironmercury bonds in complexes of ferrocene with mercuric chloride from mössbauer spectroscopy

Abstract Novel Mossbauer spectra of ferrocene/mercuric chloride adducts are reported, displaying anomalously high quadrupole splittings, which are interpreted as strong evidence for FeHg bonding. The results are discussed in conjunction with tilting of the cyclopentadienyl rings.

Mössbauer studies on ferrocene complexes : II. Ironhydrogen-bonded complexes of ferrocene

Abstract Ironhydrogen-bonded complexes of ferrocene have been studied by Mossbauer spectroscopy. The high quadrupole splittings are interpreted in terms of ring-tilting and charge distribution and compared with results from ferrocene mercuric chloride adducts. Correlations are found between isomer shift and quadrupole splittings in the compounds studied.

Base-catalysed cleavage of allylic derivatives of group IVA elements. I

Abstract The mechanism of alkali cleavage of 3-phenallyl derivatives of silicon, germanium and tin in aqueous alcoholic media has been studied spectrophotometrically Both solvent isotope and primary salt effects are consistent with a rate determining S N 2 attack on the metal or metalloid atom with the expulsion of a carbanion. The product of reaction is β-methyl styrene, indicating that proton attack on the carbanion has occurred in the 3 position. The reaction appears to be subject to rather large steric effects. In aqueous alcohol, the triethyl tin derivatives reacted faster than either the silicon or germanium analogues, the latter two reacting too slowly to enable an estimate of relative rates to be made. In aqueous dimethyl sulphoxide the order of reactivity was found to be Et 3 Sn ⪢ Et3Si Et 3 Ge. Some spectroscopic evidence for homoallylic interaction in the 3-phenallyl series is presented. This interaction has been invoked to explain the greater reactivity of 3-phenallyl compounds compared with their benzyl analogues.

Synthesis and spectroscopic studies of some novel bicyclic organotin compounds

Abstract A number of new bicyclic organotin compounds have been synthesised by treating the corresponding organic halide with (trialkyl- or triarylstannyl)sodium in liquid ammonia. syn -7-Bromo-2-norbornene yielded mainly the anti -7-trimethyltin derivative when treated with (trimethylstannyl)sodium, but gave a tricyclic compound on reaction with (triphenylstannyl)sodium. anti -7-Bromobenzonorbornadiene gave a syn/anti mixture of the trimethylstannyl analogue together with that appeared to be a tricyclic derivative. 7-Chloro-2,5-norbornadiene readily gave the coreresponding 7-triphenylstannyl compound, but its trimethyltin analogue was formed only with difficulty and was unstable. The compounds were characterised by the PMR spectra, and the mechanism of formation is discussed. The addition of trimethyltin hydride to 2,5-norbornadiene resulted in a mixture of exo and endo -5-norbornenyl derivativevs. 13 C NMR, Mossbauer and infrared spectroscopy were used in a search for donor-acceptor interactions between the tin atom and CC double bonds situated in stereochemically favourable positions, viz . 7-(trimethyl- and triphenylstannyl)-2,5-norbornadiene, and also endo -5-(trimethylstannyl)-2-norbenene. None of the spectroscopic techniques used revealed any evidence for this effect.

Mössbauer studies on ferrocene complexes: XVII. Ferrocenylamines and ferrocenylphosphines☆

Abstract 57Fe Mossbauer data are reported for some ferrocene derivatives in which the ferrocenyl group is bonded to N And P, and are considered in the light of 13C NMR and cyclic voltammetry (CV) data. They highlight the difference in the interaction between the ferrocenyl unit and the exocyclic nitrogen or phosphorus atom.

Mössbauer studies on ferrocene complexes : IV. Substituent effects in ferrocenyl-carbenium ions

Abstract The structure of secondary ferrocenyl-carbenium ions of the type C5H5FeC5H4???HR have been investigated by 1H NMR spectroscopy in CF3CO2H and by 57Fe Mossbauer spectroscopy of solid solutions of the same medium. As with primary ions (R  H) exalted values of quadrupole splittings (QS) were observed for R  CH3, C6H5, indicative of iron participation via ϵ2 orbitals. For the aromatic series (R  p-C6H4X), QS values decreased as the electron donating power of the substituent increased, due to increased stabilisation via the phenyl ring at the expense of iron participation. It is postulated that exalted QS values (i.e. greater than that of solid ferrocene itself) in ferrocene systems are due to electron withdrawal from iron-based orbitals ϵ2, whereas low QS values are due to electron withdrawal via ring-based orbitals ϵ1. The NMR data is discussed in terms of steric hindrance to coplanarity of the phenyl ring w ith the vacant sp2 orbital of the carbenium ion. Dialcohols of the type Fe(C5H4CHOHR)2 gave only mono-carbenium ions.

Mössbauer studies on ferrocene complexes : V. Protonation of ferrocenyl ketones

Abstract The structure of protonated ferrocenes has been investigated using 1 H NMR and 57 Fe Mossbauer spectroscopy. The ketones were fully protonated in CF 3 CO 2 H and in 70% H 2 SO 4 /H 2 O. In more concentrated sulphuric acid (⪢90% H 2 SO 4 /H 2 O) rapid heteroannular sulphonation occurred. No evidence was obtained of any iron protonation in these systems. For the para substituted aromatic derivatives C 5 H 5 FeC 5 H 4 COC 6 H 4 X the NMR data indicates steric inhibition to resonance. 1,1-Diketones are doubly protonated in strongly acid media (98% H 2 SO 4 , CF 3 SO 3 H). Mossbauer data on the solid ketones showed a decrease in quadrupole splitting (QS), relative to ferrocene itself, of about 0.12 mm s −1 for each successive acyl function added. For solid solutions of the protonated ketones in CF 3 CO 2 H this decrease (ΔQS) was much larger at about 0.28 mm s −1 . The results are interpreted as involving electron withdrawal from ring-based orbitals (ϵ 1 ), rather than the iron-based orbitals (ϵ 2 ). In the aromatic series, ΔQS was significantly smaller for electron withdrawing substituents.