Complex formation equilibria of ligands with metal ions of biomedical interest
Bibliographic record
Abstract
In a healthy situation, the body is provided with homeostatic mechanisms and buffers to maintain physiological concentrations of free metal ions, thus preventing their abnormal decompartmentalization, release and trafficking. The main reasons for the anomalous accumulation of non-essential metal ions in the body are environmental exposure and administration of metallodrugs for therapy or diagnosis, which may cause competition for biometals, generation of oxidative stress and disregulation of several metal-enzyme systems. Inorganic medicinal chemistry has to deal with the introduction of metal ions in the body, but also with their removal or passivation through the use of chelators. In these terms, thermodynamics and kinetics of complex formation are very important for a correct understanding of the role of metal ions in human diseases. \nDuring my PhD work, some new ligands were synthesized and their complex formation equilibria with toxic, essential and other metal ions of biomedical interest were studied. \nIn particular, some derivatives of kojic acid have been synthesized and their protonation and chelating properties toward the target metal ions Fe3+ and Al3+, and the two essential Cu2+ and Zn2+ have been characterized. Furthermore, the complex formation equilibria of some drugs actually in clinical use with the essential metal ions Cu2+ and Zn2+ were studied to give evidence of their possible implications in copper chelation. Moreover, the tyrosinase inhibitory properties of the kojic derivative[1] (5-hydroxy-4-oxo-4H-pyran-2-yl)methyl3-({[(5-hydroxy-4-oxo-4H-pyran-2yl)methoxy]carbonyl} amino)propanoate and its complex formation equilibria with copper have been studied, since the inhibitory effect may result from the interaction with copper ions in the active center of the enzyme. \nThis thesis is divided in an Introduction, dedicated to a description of metals, to their chemistry and their overload or deficiency, to chelation therapy, to the characteristics of chelators for metal overload treatment and to the improvements induced on some pathological conditions in diabetic patients. Further attention is devoted to tyrosinase inhibition and radiopharmaceutical labelling. An Experimental part describes the synthesis of new chelators and the methods used for a complete characterization. In the section Results and Discussion the determination of protonation constants for all ligands, together with that of their complex formation constants with metals of interest like Fe3+, Al3+, Ga3+, Cu2+ and Zn2+, is presented, in order to evaluate their therapeutic application in metal overload diseases. Complex stability studies of two new ligands with lanthanum to be used in the treatment of bone disorders are also presented as a part of a collaboration during my three month period at the University of British Columbia, Vancouver-Canada. A brief section Conclusions summarizes the presented results.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".