Helen Elaine Howard-Lock

Chirality in antirheumatic drugs

Use of chiral molecules in clinical practice may cause problems because different chiral forms of a drug (enantiomers) may have different biological activities--yet clinicians have little awareness of these risks. After discussion of the chemical conventions used to describe chirality, examples of the influence of chirality on the efficacy and toxicity of antirheumatic drugs are given. It is recommended that single enantiomers should be used in biological experiments and clinical trials.

d-penicillamine: Chemistry and clinical use in rheumatic disease

The discovery of D-penicillamine and its uses in medicine are reviewed. Chemical-physical properties are discussed, and the molecular structure of D-penicillamine and several of its reaction products are illustrated. Examples of its three main types of biochemical reactions--sulfhydryl-disulfide exchange, thiazolidine formation, and metal chelation are included. Trials of D-penicillamine in RA patients are reviewed critically. The administration of the drug is discussed in detail, including dosages, clinical and laboratory responses, patterns of adverse side effects or toxicity, drug-induced autoimmune diseases, indications and contraindications, and the monitoring and management of patients.

Cyclopentanone: Inversion doubling in the 3300Å 1A2-X1A1 absorption system

Abstract Analysis of the 3300Aabsorption systems of cyclopentanone and two of its deuterated isomers show that in the excited state, the carbonyl bond length has increased to 1.35Afrom its value of 1.24Ain the ground state, and that the oxygen atom is bent out of the C 5 -C 1 -C 2 plane, producing an inversion doubling of the carbonyl out-of-plane vibrational mode in the excited state. The out-of-plane angle is ∼32° from band contour analysis, and 35° at the potential minima from a fit to the calculated eigenvalues for a Gaussian-type function. The barrier to inversion of the carbonyl group in the excited state is ∼700 cm −1 for all three isomers. The absorption system is due to an n → π * , 1 A 2 - X˜ 1 A 1 electronic transition. The electronic origins coincide with bands at 30 514.0/30 487.3/30 460.5 cm −1 for cyclopentanone, the α-α-α′-α′-d 4 , and the d 8 isomers respectively. It is believed that the transition acquires intensity by an additional vibronic path compared with the analogous transition in formaldehyde. This path involves excitation of the ring-puckering mode, whose frequency increases from 236/220/189 cm −1 in the ground state to 284/268/264 cm −1 in the excited state.

Cyclopentanone: The vibrational spectra of some deuterated isomers

Abstract The infrared and laser Raman spectra of cyclopentanone, cyclopentanone-α,α,α′,α′- d 4 , and cyclopentanone- d 8 have been measured. From a comparative analysis of the spectra of these three isomers, together with those of related molecules, assignments have been made for the 36 normal frequencies of vibration of the molecule.

Structures of gold(i) and silver(i) thiolate complexes of medicinal interest: a review and recent results.

We review the crystal structures, electrospray ionization mass spectra (ESI-MS) data and chiral HPLC data for the racemic and optically pure mononuclear AuL2 complexes, and for racemic [AuLI]n and optically pure [AgLII]n polymers (LI = thiomalate, LII = D-penicillamine). We postulate an equilibrium between polymeric, mononuclear and free ligand species for [AuLII]n (gold sodium thiomalate or GST). The ESI-MS results clearly show a tetrameric principal species in the 1:1 gold polymers, [AuLI]n. For the 1:1 silver: D-penicillamine complex, [AgLII]n, a non-molecular crystal of double helical structure, the ESI-MS results show multi-ligand-silver species, including tetramers, pentamers and hexamers. Other, relevant gold, silver and copper complexes are compared.

The vibrational spectra of pertechnyl chloride, TcO3Cl

Abstract The vibrational spectra of pertechnyl chloride have been measured over a temperature range and compared with those of perrhenyl chloride. There is considerable similarity. In addition the spectra are extremely similar to those of Tc 2 O 7 . It is postulated that splitting of the vibrational bands in both solid TcO 3 Cl and ReO 3 Cl at very low temperatures was caused by a phase change.

The crystal structure of racemicdl-penicillamine and a spectroscopic study ofd-(−)-penicillamine

The X-ray crystal structure of a racemic mixture of D- and L-penicillamine has been determined. Crystals are monoclinic,P21/c (No. 14), with cell dimensionsa=11.624(3),b=5.919(1),c=11.482(2) Å,β=114.48(2)°, andZ=2, based on the racemate. The structure was determined by standard methods and refined toR1=0.0666,R2=0.0726 for 985 independent reflections. Bond lengths and bond angles do not differ from those in similar structures. Mass spectra and1H and13C NMR spectra are reported ford-penicillamine, and detailed infrared and Raman spectra are reported for solidd-penicillamine hydrochloride,d5-d-penicillamine hydrochloride,d-penicillamine,d4-d-penicillamine, anddl-penicillamine. The Raman spectrum ofd-penicillamine in H2O solution as a function of pH is also reported.

Gold complex research in medical science. Difficulties with experimental design

Despite the use of gold complexes in modern medicine for over 100 years and the use of gold complexes in the management of rheumatoid disease for more than 60 years, the definitive mechanisms of action for efficacy and for toxicity have not been established.Gold is a group 1b metal in the periodic table with several oxidation states but it is only Au(I) which is active in the biological milieu. Gold sodium thiomalate is not only a polymeric structure, but also has the chiral ligand, thiomalic acid. Gold sodium thiomalate thus can exist in several different physical states which may have different biological activity. In addition the pharmacokinetic profile of gold complexes has been of little value in the understanding of either the mechanism of action, efficacy or toxicity for both the injectable and the oral gold complexes. Many authors have misinterpreted research data on the activities of gold complexes because they compared gold complexes of different structures, and gold complexes which exist at different pH.Experimental work in our laboratory has identified that gold sodium thiomalate is a mixture and can exist as either a yellow or a colourless solution. These have some similar but several different biological activities.Many factors contribute to the lack of understanding of the action of gold complexes. Some of these factors are related to the wide variation in physical structure and biological activities exhibited by these compounds.

Thiomalate complexes of gold( I ): preparation, characterization and crystal structures of 1∶2 gold to thiomalate complexes

The preparation and characterization of 1∶2 gold to thiomalate complexes, as ammonium salts, has been described. The crystal structures of both racemic and optically pure samples are described and compared. In each case, the gold atom is linearly co-ordinated to two ligand sulfur atoms. Bond lengths and angles are normal.

Studies of the rhenium oxygen bond—V. The vibrational spectra and force constant analysis of K3ReO2(CN)4, K2ReO2(13CN)4 and K3Re18O16O(CN)4 and some comments on the vibrational spectra of Re2O3(CN)84−

Abstract The i.r. spectra (4000-50cm −1 ) and laser Raman spectra of solid K 3 ReO 2 (CN) 4 , K 3 ReO 2 ( 13 CN) 4 (99% 13 C enriched), and K 3 Re 18 O 16 O(CN) 4 (20% 18 O enriched) have been measured. An assignment of the vibrational frequencies for the D 4h ion has been made. A normal coordinate analysis was carried out. The refined force constants, and potential energy distributions are tabulated. A symmetry factoring treatment of Re-O force constants has also been shown to be valid for the ReO 2 (CN) 3− 4 ion, and has been used for the Re 2 O 3 (CN) 4− 8 ion.