Sinteza, karakterizacija i ispitivanje mehanizma supstitucionih reakcija kompleksa nekih jona prelaznih metala

Abstract

Sinteza novih kompleksnih jedinjenja jona prelaznih metala i njihova karakterizacija od velikog su značaja ne samo u koordinacionoj hemiji, već i u bioneorganskoj i medicinskoj hemiji. Primena kompleksa jona prelaznih metala u biologiji, farmaciji, medicini, poljoprivredi je predmet istraživanja mnogih naučnika. Neki joni metala su gradivni elementi biomolekula, dok neki ulaze u sastav mnogobrojnih lekova koji se već dugi niz godina koriste u medicini. Otkrićem antitumorskog dejstva cisplatine od strane B. Rozenberga 60-ih godina dvadesetog veka otpočela je prava revolucija u terapiji teških bolesti lekovima na bazi kompleksa jona prelaznih metala. Mnogobrojna istraživanja u ovoj oblasti dovela su do toga da se danas pored cisplatine i neki drugi kompleksi Pt(II), kao što su karboplatina i oksaliplatina, intenzivno koriste u hemoterapiji. Poslednjih 40 godina veliki broj drugih kompleksa platine sintetisan je sa ciljem da se postigne bolja aktivnost u odnosu na cisplatinu. Takođe, već duži niz godina predmet istraživanja mnogobrojnih naučnika su derivati pirazola i njihovi kompleksi sa prelaznim metalima. Pirazoli su vrlo pogodni za sintezu raznih organskih jedinjenja koja mogu imati različitu primenu. Od važnijih proizvoda mogu se istaći biološki aktivni molekuli koji se koriste u medicini kao aktivne komponente nekih komercijalnih lekova, dok se neki koriste u poljoprivredi kao pesticidi (herbicidi, fungicidi, insekticidi, itd.). Jedan od glavnih ciljeva bioneorganske hemije je razjašnjavanje mehanizama delovanja kompleksa jona metala u biološkim sistema. Za ispitivanje kinetike i mehanizma supstitucionih reakcija kompleksa Pt(II) kompleksi Pd(II) predstavljaju pogodne modele, uzimajući u obzir činjenicu da kompleksi Pd(II) reaguju 103-105 puta brže od analognih kompleksa Pt(II). Zbog velikog afiniteta prema sumpor- i azot- donorskim ligandima, kao i velike reaktivnosti, selektivnost kompleksa Pd(II) prema biomolekulima je mala, što ograničava upotrebu ovih jedinjenja kao antitumorskih agenasa. Međutim, poslednjih godina utvrđeno je da neki kompleksi Pd(II) ipak poseduju antitumorsku aktivnost.

The synthesis of new complex compounds with transition metal ions and their characterization are of great importance, not only in coordination chemistry, but also in bioinorganic chemistry and medicinal chemistry. Application of transition metal complexes in biology, pharmacy, medicine, agriculture is subject of research of many scientists. Some of metal ions are building blocks of biomolecules, while some of them are part of many drugs that are already used for many years in medicine. Discovery of antitumor activity of cisplatin by B. Rosenberg during the 60’s of the twentieth century started a real revolution in treatment of severe disease drugs based on transition metal ion complexes. Most of results in this field have contributed that today, beside cisplatin, other complexes of Pt(II), such as carboplatin and oxaliplatin, are used extensively in chemotherapy. In the past 40 years a large number of other platinum complexes were synthesized in order to obtain a compound with better activity than cisplatin. Also, for many years, pyrazole based compounds and their transition metal complexes have attracted considerable research interest. The pyrazoles are very suitable for obtaining various organic compounds, which can have different applications. The most important products are biologically active molecules which are used in medicine as active components of some commercial drugs, while some are used in agriculture as pesticides (herbicides, fungicides, insecticides, etc.). One of the main aims of bioinorganic chemistry is to clarify the mechanism of interactions of metal complexes in biological systems. For the study of kinetics and mechanism of substitution reactions of Pt(II) complexes, Pd(II) complexes are very suitable models, taking into account the fact that Pd(II) complexes react 103-105 times faster than their Pt(II) analogous. Due to the very high affinity for sulfur and nitrogen donor ligands, as well as very high reactivity, the selectivity of Pd(II) complexes toward bio-molecules is small. In addition, these facts limit the application of Pd(II) complexes as antitumor agents. However, in recent years it was established that some complexes of Pd(II) possess antitumor activity.