Antineoplastic drug occupational exposure: a new integrated approach to evaluate exposure and early genotoxic and cytotoxic effects by no-invasive Buccal Micronucleus Cytome Assay biomarker.

Health-care personnel handling antineoplastic drugs could be at risk for adverse health effects. We aimed to evaluate genotoxic and cytotoxic effects of antineoplastic drug exposure of personnel preparing and administering such drugs in three Oncology Hospitals in Italy enrolling 42 exposed subjects and 53 controls. Furthermore, we aimed to study the possible influence of XRCC1 and hOGG1 DNA repair genes polymorphisms on genotoxicity induced on buccal cells. We performed workplace and personal monitoring of some drugs and used exposure diary informations to characterize the exposure. Urinary 5-FU metabolite (α-fluoro-ß-alanine) was measured. Buccal Micronucleus Cytome (BMCyt) assay was used to evaluate DNA damage and other cellular anomalies. GEM and 5-FU contamination was found in 68% and 42% of wipe/swab samples respectively. GEM deposition was found on workers' pads while no α-fluoro-ß-alanine was found. BMCyt-assay showed higher genotoxicity and cytotoxicity on nurses administering antineoplastics than on preparators and controls. Among micronucleus (MN) positive (with MN frequency higher than 1.5‰) exposed subjects, the percentage of those carrying XRCC1 mut/het genotype was higher than in MN positive-controls. Using the sensitive BMCyt assay, we demonstrated that handling antineoplastics still represents a potential occupational health risk for workers that should be better trained/informed regarding such risks.

Glutathionyl-hemoglobin levels in carotid endarterectomy: a pilot study on 12 cases clinically uneventful.

Aim: Carotid endarterectomy is a widely accepted procedure for stroke prevention, and carotid clamping is a necessary surgical step. Glutathionylated haemoglobin (HbSSG) has been recently employed as a biomarker of oxidative stress, its level being increased under several conditions, including hypoxia. This study aims to evaluating whether HbSSG level in peripheral and/or jugular blood is affected during carotid surgery under normal routine operative conditions. Methods: This study enrolled 13 consecutive patients undergoing elective carotid endarterectomy under general anesthesia. At different times during surgery, blood was taken simultaneously from both a peripheral vein and the jugular vein ipsilateral to the clamped carotid. HbSSG was measured in RBC hemolysates by MALDI-ToF mass spectrometry in each sample. Results: Three patients showed a complex pattern of rise and fall of HbSSG levels in different time periods before, during and after surgery. They also showed statistically significant differences between peripheral and jugular blood, with mean HbSSG levels in jugular blood higher by approx. 30% than those of peripheral blood at the end of the period of carotid clamping. In all three patients HbSSG levels fell to pre-clamping values within 2 min from removal of carotid artery clamp. Conclusion: Although effective routine drug management allowed brain safety during carotid clamping time, a number of patients showed a fast modification over time of the HbSSG levels in jugular blood, suggesting that "resident" cerebral biochemical protection mechanisms could play some role to compensate clinically silent brain oxidative stress.

Exposure to priority organochlorine contaminants in the Italian general population. Part 2: Fifteen priority polychlorinated biphenyl congeners in blood serum.

Concentrations of 36 polychlorinated biphenyl (PCB) congeners were measured in serum of 372 Italian residents of general population living in Novafeltria, Pavia, and Milan. Total PCB level differed significantly between these sites (p < 0.0001) with median concentrations of 836.50, 1354.57, and 2062.08 pmol/g lipid, respectively. However, there is no evidence for the difference in distribution of total PCB levels by genders. Total dioxin-like PCBs differed significantly (p < 0.0001) between the sites (median 109.78, 50.88, and 166.99 pmol/g lipid, respectively) and genders of Novafeltria and Pavia (p = 0.011 and 0.009, respectively). PCB 138, 153, 170, and 180 differed significantly between the places of residence (p < 0.0001) with higher values in Milan population. In the overall population, total PCB and PCB 138, 153, 156, 170, and 180 correlated positively with age (correlations range between 0.320 and 0.569, p < 0.0001). In Novafeltria, the correlations ranged between 0.545 and 0.670, and in Pavia, the correlations ranged between 0.516 and 0.666. In Milan, correlations with age range between 0.327 and 0.417 for total PCB and congeners 138, 153, and 180. With an exception of PCB 170, there was no evidence of significant difference in the distribution of most abundant PCB congeners and total PCB across the body mass index categories.

Exposure to priority organochlorine contaminants in the Italian general population. Part 1. Eight priority organochlorinated pesticides in blood serum.

Despite extensive use of organochlorinated pesticides (OCPs) such as dichlorodiphenyltrichloroethane (DDT) in Italy in the 1940s to 1970s, especially for public health control of malaria mosquitoes, information on their exposure levels among the general population is limited. These OCPs can be a source of health risk to human. A total of 137 blood samples were collected from residents of the general population of three Italian towns, Novafeltria, Pavia and Milan, to determine the levels of eight OCPs in blood serum. The concentrations of beta-hexachlorocyclohexane, hexachlorobenzene (HCB), 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethylene, 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE), 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane, 1,1-dichloro-2,2-bis (4-chlorophenyl)ethane, 1,1,1-trichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)-ethane and 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane were measured by gas chromatography-mass spectrometry. Variations in serum concentrations of OCPs with respect to place of residence, gender, age and body mass index (BMI) were evaluated by non-parametric tests. p,p'-DDE and HCB were the most abundant and major contributors of total OCP concentration. Their levels differed significantly between the three towns with a trend Milan > Novafeltria > Pavia (p < 0.0001). Females had significantly higher concentrations of HCB and p,p'-DDE than males in the overall population sample. HCB concentrations were significantly higher in females than in males of Milan (p = 0.029). We observed positive correlations of p,p'-DDE and HCB with age in Novafeltria subjects (r = 0.468, p = 0.004). Total OCP concentrations differed significantly across BMI categories (p = 0.018) in overall population. We have demonstrated a clear pattern of the main OCPs in a fairly large population. Generally, our study provides information on OCPs exposure among the Italian general population and provides indications for further investigations.

[Plant protection products: new tools for exposure and risk assessment in agriculture]. / Antiparassitari: nuovi strumenti per la valutazione dell'esposizione del rischio in ambito agricolo.

Our experience in assessment and management of chemical risk in agriculture consists of three lines: i) definition and modeling of the relationships between different exposure determinants to create the possibility of doing risk assessment without measurements ii) identification, from the Acceptable Operator Exposure Levels (AOEL), of provisional biological exposure indices for pesticides; iii) identification of analytical approaches adequate for the production of the measures needed to support the above mentioned activities starting from the use of multi-residue methods, allowing the determination in one run of several active ingredients and metabolites.

[Physically-based model of pesticide application for risk assessment of agricultural workers]. / Valutazione del rischio nell'applicazione in campo di prodotti fitosanitari attraverso modelli a base fisica per la stima dell'esposizione.

Due to their unavoidable toxicity to non-target organisms, including man, the not of Plant Protection Products requires a thorough risk assessment to rationally advise safe use procedures and protection equipment by farmers. Most information on active substances and formulations, such as dermal absorption rates and exposure limits are available in the large body of regulatory data. Physically-based computational models can be used to forecast risk in real-life conditions (preventive assessment by 'exposure profiles'), to drive the cost-effective use of products and equipment and to understand the sources of unexpected exposure.

Use of total reflection X-ray fluorescence (TXRF) for the evaluation of heavy metal poisoning due to the improper use of a traditional ayurvedic drug.

An Indian patient referred to Clinica del Lavoro 'L.Devoto' of Milano showed clinical signs of heavy metal poisoning, possibly related to a sustained 6-month use of approx. 3 g/day of a traditional preparation (a whitish powder with a 'mineral' appearance) to treat urological problems. To confirm the causal relationship between the disease and the use of such product, metal testing was performed on the patient's hair and the ayurvedic remedy samples by total reflection X-ray fluorescence (TXRF). For TXRF analysis 1-cm cut of the patient's hair was directly deposited onto the quartz glass sample carrier, then 10 microl of nitric acid 65% were added and dried in air. TXRF showed high versatility, rapid and simultaneous element detection, and short analysis time, thus supporting a wider use in emergency medicine and in forensic analyses.

Aluminum determination in biological fluids and dialysis concentrates via chelation with 8-hydroxyquinoline and solvent extraction/fluorimetry.

We describe a simple, rapid, and sensitive fluorescence method for measurement of aluminum (Al) in human biological fluids, in dialysis solutions, and in tap water, which uses 8-hydroxyquinoline for ion chelation. The fluorescence intensity of the toluene-extracted metal chelate (excitation wavelength, 380 nm; emission wavelength, 504 nm) remains unchanged for over 48 h at room temperature. Fluorescence intensity is a linear function of the concentration of Al in the 2-1000 microg/L range with detection limits of 0.7-2 microg/L. A large excess of other ions normally found in biological fluids does not interfere in Al determination. The method developed was successfully used in assaying Al in serum and urine of reference subjects, in serum samples from patients undergoing long-term dialysis, and in dialysis solutions. Al concentrations, measured by this fluorimetric procedure, were compared with those obtained by Zeeman graphite-furnace atomic absorption spectrometry. A correlation coefficient of 0.98 was obtained. The proposed method could be used for routine analysis in clinical laboratories for accurate determination of aluminum in aqueous or biological fluids.

[Evolution of industrial toxicology toward vanishing doses and the human genome]. / Evoluzione della tossicologia industriale tra dosi effimere e genoma umano.

BACKGROUND: This article aims to discuss the influence that the application of the recent discoveries in genomics will have on the theory and practice of industrial toxicology in developed post-industrial countries. It is stressed that the recent advances in toxicogenomics can be integrated into the existing wealth of knowledge on the toxic properties of industrial chemicals to improve the efficacy of prevention of toxicological risk. METHODS AND RESULTS: The understanding of the biochemical and physiological mechanisms underlying susceptibility or resistance to the toxic effects of industrial xenobiotics, and in particular to carcinogens, allows us to split the epidemiologically derived relationship linking the frequency of disease in the exposed population to the level of workplace contamination into a set of sequential sub-relationships linking: a) the exposure level to that of workplace contamination; b) the internal dose to the exposure level; c) the biological effect (e.g., measured through biochemical markers of early effect) to the internal dose; d) the frequency of disease to that of observation of early biochemical effects. Each of the cited relationships is affected by a degree of uncertainty due to the variability of biological response among the examined individuals, which in turn requires a definition of the statistical limits for the association functions between the variables. As a consequence, the possibility of investigating the individual biochemical and physiological steps in the causal mechanism that links toxic exposure to disease does not necessarily lead to an increase in the information potential of biological monitoring, since the uncertainty due to inter-individual variability is amplified through the sequence of causal relationships to the point that the data from biological monitoring become valueless with regard to the prediction of the frequency or probability of disease. This is particularly true when exposure to 'low doses' is investigated, as is now increasingly frequent in post-industrial developed countries, where workplace contamination is now greatly reduced to levels which may be borderline with those in the general environment. Thus at the low-dose end of the range of contamination and exposure values there is an area where, for statistical reasons consequent to the heterogeneity of examined populations, a quantitative prediction of internal exposure due to environmental contamination, of biological adverse effects due to exposure levels and of frequency of disease due to the extent or frequency of biological effects is no longer reliably possible. This in turn impairs the preventive efficacy of biological monitoring. CONCLUSIONS: A closer integration between industrial toxicology and state-of-the-art molecular genetics derived from the recent sequencing of the human genome is the way to overcome the limitations described. In particular, the individual subjects in the examined populations can be classified with regard to some genetically controlled characters relevant to the biotransformation of xenobiotics and to DNA repair and the statistical analysis of data can be performed on more homogeneous subpopulations, in order to decrease inter-individual variability of biochemical and physiological response. This in turn increases the predictive power of the biological markers, both of dose and effect, and improves the efficacy of prevention, e.g., by highlighting oversensitive subpopulations or lifestyles which can increase the risk of occupational and environmental disease.

[Evaluation of the neurotoxic and nephrotoxic effects following long-term exposure to metallic mercury in employed at a chlorine/sodium-hydroxide plant]. / Valutazione degli effetti neurotossici e nefrotossici conseguenti all'esposizione a lungo termine a mercurio metallico dei lavoratori addetti agli impianti Cloro-Soda.

OBJECTIVES: Within the frame work of a wide multicentre study, a sub-study was developed in order to explore the occurrence of early effects on the central nervous system, on the kidney and on the neuro-immune system in the workers of a chloro-alkali production plant exposed to metallic mercury at airborne concentration levels lower than 0.025 mg/m3 (TLV-TWA). They were compared to a control population of employees of the same huge petrochemical plant with different job that did not implicate exposure to mercury vapors. Specifically, the study aimed at revealing the occurrence of early effects on the central nervous system related with mercury exposure, as can be assessed through neurophysiological and neurobehavioral tests. METHODS: The excretion of urinary mercury was measured by atomic absorption spectrometry. The study of renal function was assessed by measurement of the urinary excretion of some high and low molecular weight protein markers (albumin, beta 2-microglobulin, retinol-binding protein, fibronectin, specific proximal tubule brush border antigens, N-acetyl-beta-D-glucosaminidase). The neurobehavioral status of the study subjects was assessed by means of several test parameters (Simple Reaction Time, Color Word Vigilance Test, Symbol Digit, Finger Tapping, Mood Scale of Kjellberg and Iwanowski, Subjective symptoms questionnaire (QSS), Luria Nebraska Motor Scale, Branches Alternate Movement Task and Tremometry). RESULTS: The values of urinary excretion averaged 12 +/- 8 micrograms Hg/g of creatinine for the exposed workers group (n = 38), while for the reference group (n = 34 cases) urinary excretion was statistically lower, averaging 4 +/- 6 micrograms Hg/g of creatinine. Neither the parameters selected for the assessment of renal functions, nor those chosen to probe the neurobehavioral status of the probands revealed statistically reliable differences between the group of exposed workers (length of exposure: range 1-34 years) and the control group. Nevertheless, some minor but still statistically reliable correlations were found between some neurobehavioral parameters and some demographic variables describing the whole group of tested workers, but not to the level of occupational exposure to mercury. CONCLUSIONS: The results of the study confirm the lack of toxic effects of clinical importance on the central nervous system and on the kidney for values of mercury urinary excretion lower than the suggested index of biological exposure (IBE) of 35 micrograms Hg/gram of creatinine.

Separation methods for methotrexate, its structural analogues and metabolites.

Methotrexate (MTX) is the prototype folate antagonist cytotoxic drug, employed in the therapy of solid tumors and leukaemias, and recently also as an immunosuppressive agent in organ transplantation, in the treatment of some autoimmune diseases and in the therapy of severe asthma. MTX is one of the very few antineoplastic drugs the therapeutic concentration monitoring of which is currently employed in clinical practice and can be routinely measured in biological samples by a number of different analytical techniques, among which are immunoenzymatic and chromatographic methods. Each technique has of course its own advantages in terms of sensitivity, specificity, speed, cost and level of expertise required. Along with therapeutic drug concentration monitoring and clinical pharmacology, fundamental research into the mechanism of action of antifolate drugs is still a field which requires the measurement of MTX, of its new analogues and of their metabolites in biological samples. This review summarizes the instrumental conditions and the performance of several published chromatographic methods employed to measure MTX, its metabolites and some analogues in clinical and biological research. More than 70 papers describing chromatographic assays for MTX and its metabolites have been published in the literature between 1975 and 2000. A wide array of experimental conditions for sample preparation, analyte separation and detection have been employed. According to their chemical properties, MTX, its metabolites and analogue drugs present in several biological samples (plasma, serum, saliva, urine, cerebrospinal fluid, tissue specimens) can be extracted, separated and detected under a variety of chromatographic conditions, i.e. on different stationary phases, under a wide choice of mobile phase conditions (acidic or neutral, employing ion-pair or micellar chromatography), followed by several detection techniques (UV-Vis spectrophotometry, pre- or post-column oxidation and fluorimetry, electrochemistry, mass spectrometry). Optimized methods allow simultaneous measurement within a few minutes of the plasma levels of MTX and its main metabolites at concentrations in the low-nM range. One special field which needs sensitive, fast and inexpensive methods for the detection and measurement of MTX is the monitoring of contamination in workplace environments, such as pharmaceutical industries and oncological hospital pharmacies, and in sewage waters. The measurement of the intracellular gamma-oligo-glutamate metabolites of biological folates, of MTX and of some analogue drugs is of great importance in basic pharmacological research. The existence of empirical quantitative relationships between the retention of individual oligomers under different chromatographic conditions and the number of added glutamic acid units allows identification of the metabolites even when authentic standards are not available.

Measurement of surface contamination by certain antineoplastic drugs using high-performance liquid chromatography: applications in occupational hygiene investigations in hospital environments.

Within the context of continuing interest in occupational hygiene of hospitals as workplaces, the authors report the results of a preliminary study on surface contamination by certain antineoplastic drugs (ANDs), recently performed in eight cancer departments of two large general hospitals in Milan, Italy. Since reliable quantitative information on the exposure levels to individual drugs is mandatory to establish a strong interpretative framework for correctly assessing the health risks associated with manipulation of ANDs and rationally advise intervention priorities for exposure abatement, two automated analytical methods were set up using reverse-phase high-performance liquid chromatography for the measurement of contamination by 1) methotrexate (MTX) and 2) the three most important nucleoside analogue antineoplastic drugs (5-fluorouracil 5FU, Cytarabin CYA, Gemcytabin GCA) on surfaces such as those of preparation hoods and work-benches in the pharmacies of cancer wards. The methods are characterized by short analysis time (7 min) under isocratic conditions, by the use of a mobile phase with a minimal content of organic solvent and by high sensitivity, adequate to detect surface contamination in the 5-10 micrograms/m2 range. To exemplify the performance of the analytical methods in the assessment of contamination levels from the target analyte ANDs, data are reported on the contamination levels measured on various surfaces (such as on handles, floor surfaces and window panes, even far from the preparation hood). Analyte concentrations corresponding to 0.8-1.5 micrograms of 5FU were measured on telephones, 0.85-28 micrograms/m2 of CYA were measured on tables, 1.2-1150 micrograms/m2 of GCA on furniture and floors. Spillage fractions between 1-5% of the used ANDs (daily use 5FU 7-13 g; CYA 0.1-7.1 g; GCA 0.2-5 g) were measured on the disposable polythene-backed paper cover sheet of the preparation hood.

High-performance liquid chromatography of methotrexate for environmental monitoring of surface contamination in hospital departments and assessment of occupational exposure.

In the frame of applicative research in occupational hygiene of hospital workplaces, we investigate hospital indoor contamination as a consequence of the use of antineoplastic drugs (ANDs), with the purpose of assessing exposure of medical and nursing personnel to potentially harmful doses of ANDs, and ultimately of yielding advice on safe operating procedures for manipulation of ANDs in hospitals and in house-care of cancer patients. Among the large number of currently employed ANDs, methotrexate (MTX) has been selected as a tracer of surface contamination, on the basis of its wide use in therapy, its ease of measurement and of its chemical properties relevant to persistence and transport in the indoor environment. MTX is a polyelectrolyte, with a high water, but lower organic solvent solubility, a negligible vapour pressure and a high chemical robustness to environmental stress, thus allowing to measure surface-to-surface carryover (e.g. from spillage or glove fingerprint) and indoor contamination due to aerosol transport (e.g. from syringe manipulation procedures). Monitoring of MTX in environmental samples such as swab washings of surfaces and objects requires an analytical method with characteristics of sensitivity, reproducibility, precision, analytical speed, ease of automation and robustness. We have therefore developed an analytical procedure which employs simple short-column RP-HPLC with UV detection, automated sample injection and a close analogue internal standard for improved precision and solid-phase extraction (SPE) for sample concentration. Our method has proven suitable for detecting traces of MTX on a wide variety of surfaces and objects, with a limit of quantification in the range of 50 microg/dm3 for direct injection of unconcentrated washings, corresponding to the possible detection of surface contamination as low as 1 microg/m3 and a limit of detection in the range of 10 ng/m2 for samples as large as 100 dm3 concentrated by SPE. We present preliminary results from a recent hospital case-study, assessing the contamination level of furniture and equipment in drug preparation areas. Spillage fractions as high as 5% of the employed mass (70-260 mg/day) are measured on the polythene-backed paper disposable hood cover sheet; traces of MTX in the microgram range can also be measured on floor surfaces, furniture and handles, even at a distance from the preparation hoods.

Measurement of surface contamination from nucleoside analogue antineoplastic drugs by high-performance liquid chromatography in occupational hygiene studies of oncologic hospital departments.

Within the frame of a continuing interest in occupational hygiene of hospitals as workplaces, we describe an automated analytical method by reversed-phase high-performance liquid chromatography for the measurement of contamination from the three most important nucleoside analogue antineoplastic drugs (5-fluorouracil, 5FU; cytarabin, CYA; gemcytabin, GCA) on such surfaces as those of preparation hoods and work-benches in departmental pharmacies of oncologic departments. Our method is characterized by a short analysis time (7 min) under isocratic conditions, by the use of a mobile phase devoid of organic solvent and by high sensitivity (LOD > or = 40 micrograms/l for all compounds), adequate to detect surface contamination above a threshold of 4 micrograms/m2 for wide surfaces and of 30 micrograms/m2 for small irregular objects. We present some results from a preliminary survey study recently performed in seven oncologic departments of two large general hospitals in Milan. To exemplify the contamination levels on various surfaces (such as on handles, floor surfaces and window glass panes, even far from the preparation hood), analyte concentrations in the order of 0.03-0.06 microgram/ml, corresponding to 0.8-1.5 micrograms of 5FU were measured on telephones, of 0.02-0.6 microgram/ml (0.85-28 micrograms/m2) of CYA were measured on table boards, of 0.05-10.6 micrograms/ml (1.2-1150 micrograms/m2) of GCA on furniture and floors. Spillage fractions up to 1% of the employed ANDs (employed daily 5FU 7-13 g; CYA 0.1-7.1 g; GCA 0.2-5 g) are measured on the polyethylene-backed paper disposable cover sheet of the preparation hood.

[Occupational respiratory allergopathies: environmental monitoring, air allergens, prevention]. / Allergopatie respiratorie professionali: monitoraggio ambientale, aeroallergeni, prevenzione.

The prevalence of allergic diseases has increased over recent years. Several epidemiological studies have been undertaken to determine the prevalence and the incidence of asthma and/or rhinitis caused by occupational allergens, and to investigate the factors that may affect their occurrence. In the last decade, with the development of methods to measure airborne allergens concentrations. Studies have been undertaken to examine the relationship between the levels of airborne allergens and the development of symptoms. In this paper we have reviewed the main studies published on the topic, and focused our attention on three aeroallergens (wheat flour proteins, latex and laboratory animal allergens), that have been thoroughly investigated in literature, from both clinical, epidemiological and laboratory aspects, which highlighted the major responsible allergens and tried to set up the dose-response relationship for symptoms and for sensitization. These studies cannot be directly compared to each other because of differences in the methods; however they seem to suggest that low levels of airborne allergens may be sufficient to sensitize individuals. In contrast, the evidence for a dose-response relationship between exposure and symptoms is indirect and not always clear. Further epidemiological studies are necessary. In occupational medicine the presence of asthma or of another allergic disease in a severe form is suggested as a criterion for excluding workers from their job. Workers that do not manifest allergic symptoms but are atopic should be informed about the risk of developing occupational respiratory diseases, and periodic check-ups are strongly recommended. Medical controls must not be disconnected from environmental controls. Standardized methods of measurement of airborne allergens for environmental control need to be set in order to allow comparison between studies and to adopt primary prevention measures.

A study on the solution and gas-phase chemistry of Mn(III) and Fe(III) tetraarylporphyrin complexes by fast-atom bombardment mass spectrometry : 1: Generation of molecular signals.

Fast-atom bombardment mass spectrometry has been used to investigate the chemical behavior of Fe(III) and Mn(III) tetraarylporphyrins (TAP) in both the condensed and gas phases and to clarify the mechanisms responsible for the production of positive and negative ions. The differences in the behavior of Fe(III) and Mn(III) complexes in the positive ion mode could be correlated with those in their electronic structures and knowledge of the mechanism for the generation of negatively charged species was applied to characterize the counterion coordinated to the Mn(III)-TAP. Thus, the unprecedented, complete characterization of even complex Mn(III)-TAP was made possible.

A study on the solution and gas-phase chemistry of Mn(III) and Fe(III) tetraarylporphyrin complexes by fast-atom bombardment mass spectrometry : 2: Synthesis and characterization of molecular complexes federico maria rubino.

The chemical behavior of Fe(III) and M(III) tetraarylporphorin (TAP) complexes with N-alkylimidazoles and other suitable ligands was studied by direct reaction in the fast-atom bombardment matrix and in the gas phase. The coordination reaction occurs at the metal center and yields molecular adducts of porphyry/ligand (PL) and PL, stoichiometry. Coordinative competition between free and covalently linked ligands can be used to probe the conformation of "tailed" Mn(III)-TAP.