Synthesis of CpFe(CO)(L) Complexes of Hydantoin Anions (Cp = η⁵-C₅H₅, L = CO, PPh₃), and the Use of the 5,5-Diphenylhydantoin Anion Complexes as Tracers in the Nonisotopic Immunoassay CMIA of This Antiepileptic Drug

Abstract

As part of our ongoing development of the CMIA nonisotopic immunoassay method, in which the tracers are metal carbonyl complexes and detection is by Fourier transform infrared spectroscopy, we examined the potential use as tracers of the complexes CpFe(CO)2(5,5-diphenylhydantoin) 2d and CpFe(CO)(PPh3)(5, 5-diphenylhydantoin) 3. The present study involved the synthesis of a series of hydantoin complexes (2a-2d), in particular that of the derivative of 5,5-diphenylhydantoin 2d. The structure of 2d was confirmed by X-ray crystallography. The infrared analysis, establishing the position and intensity of the characteristic metal-carbonyl peaks of complexes 2d and 3 in the 1850-2200 cm-1 region, shows that measurement of the absorbance values of these characteristic peaks will permit quantitative analysis in the picomole range, the norm for routine use in immunoassay and thus suitable for use as CMIA tracers. Cross-reaction rates of these tracers with anti-DPH specific antibodies show that 2d and 3 are both recognized by anti-DPH antibodies (cross-reaction rates 43 and 20%, respectively). In developing a CMIA of DPH with these tracers, it was found that 3, with a single, intense band at 1977 cm-1, had very promising IR characteristics for use in multiassay CMIA, but probably owing to its relatively weak affinity for the antibodies, it was not possible to develop a CMIA for DPH using this tracer. Complex 2d, however, showed better recognition by the antibodies, and using this complex as a tracer, it was possible to develop a particularly sensitive monoassay of DPH by the CMIA method.

Hartree–Fock and density functional theory study of remote substituent effects on heterolytic Fe–N bond energies of p‐G‐C6H4NHFe(CO)2(η5‐C5H5) and p‐G‐C6H4N(COMe)Fe(CO)2(η5‐C5H5)

“…In developing a carbonyl metallo nonisotopic immunoassay (CMIA) method of diphenylhydantoin, it was found that the complex CpFe(CO) 2 (5,5‐diphenylhydantoin) showed better recognition by the antibodies. And by using this complex as a tracer, it was possible to develop a particularly sensitive monoassay of diphenylhydantoin by the CMIA method . It is clear that the Fp–N bond strengths exert a major influence on the properties of iron‐nitrogen compounds, and detailed knowledge of the factors that determine the Fp–N bond strengths would greatly aid in understanding reactivity patterns in many processes …”

A Novel Field of Research: Bioorganometallic Chemistry, Origins, and Founding Principles

“…However, for an alkyne cobalt hexacarbonyl complex such as 24 in a chlorinated solvent, use of an ultralow volume gold light-pipe can provide a detection limit as low as 300 fmol (i.e 10 nM), [108], a level fully compatible with the sensitivity range required for the assay of many medications and banned drugs. This possibility led to the development of the CMIA method to assay antiepileptic medications [101,[112][113][114] and cortisol [115], a method that offers the additional potential of the simultaneous triple immunoassay, thanks to the distinct and nonoverlapping infrared bands of carefully-selected metal carbonyl probes [116]. It is also possible to displace the ν CO bands in the infrared by modifying the electron density at the metal, via substitutions of L or Cp ligands [117].…”

Luminescent fac-[Re(CO)3(phen)] carboxylato complexes with non-steroidal anti-inflammatory drugs: synthesis and mechanistic insights into the in vitro anticancer activity of fac-[Re(CO)3(phen)(aspirin)]

“…20 Synthetic drugs have also attracted great attention as targets for metal conjugation. Representative examples are half-sandwich iron-carbonyl derivatives of the antiepileptic drug 5,5-diphenylhydantoin, 21 ferrocenyl and chromium carbonyl derivatives of the anthelmintic drugs monepantel 22 and praziquantel, 23,24 manganese carbonyl derivatives of antifungal drugs ketoconazole, miconazole, and clotrimazole, 25 ferrocenyl conjugates of vorinostat 26 and ferrocenyl analogues of the anticancer drug tamoxifen. 27 Non-steroidal anti-inflammatory drugs (NSAIDs) are a very important group of medications with anti-inflammatory, analgesic, and antipyretic activity.…”