Termičko ponašanje i biološka aktivnost [co2(cl)2 tpmc](bf4)2 kompleksa

A large number of interesting Co (II) complexes with macrocyclicligands have been synthesized and the recognition of its complexes as important bioactive compounds in vitro and in vivo has aroused growing interest in these agents as potential drugs for therapeutic use in various diseases. Numerous available information on their bioinorganic properties and mode of action in several biological systems, combined with the new possibilities imposed by the development of medical chemistry, opens space for the development of a new generation of highly active drugs with minimized side effects which could add significantly to the current clinical research and practice. In this paper we attempt to present some properties of the earlier isolated the first Co(II)tpmc complex for which crystal structure confirmed chair conformation of macrocycle. Complex with formula [Co2(Cl)2tpmc](BF4)2 (tpmc = N,N',N'',N'''-tetrakis(2-pyridylmethyl)-1,4,8,11-tetraazacyclotetradecane), was studied on thermal behaviour and biological activity. TG-DTA analysis indicates that complex decomposition in a single step in the range of 365-435 °C. Investigated cytotoxic activity against two human cancer cell lines: HeLa (human cervix adenocarcinoma) and K562 (human myelogenous leukaemia). Complex was also preliminary assayed in vitro toward bacteria, fungi and mould together with the starting material for the synthesis (ligands, simple salts and solvents) as test substances. Investigated complex showed a moderate activity against strains of bacteria and were inactive against the tested fungi and mould. Minimal inhibitory concentration suppressing the visible growth of bacteria was determined. Biological investigations show the complex has significant cytotoxic potential.Poznavanje biološke uloge kobalta i prepoznavanje njegovih kompleksa kao važnih bioaktivnih jedinjenja razlozi su sve veće zainteresovanosti za potencijalnu terapijsku primenu ovih kompleksa kod različitih bolesti. Brojne dostupne informacije o njihovim osobinama i načinu delovanja u nekoliko bioloških sistema, u kombinaciji sa novim mogućnostima koje nameće razvoj medicinske hemije, otvaraju prostor za razvoj nove generacije visoko aktivnih lekova sa minimalnim nuspojavama. U ovom radu smo ispitali neke osobine ranije izolovanog Co (II) tpmc kompleksa, prvog kod koga je rendgenska strukturna analiza potvrdila da se makrciklični ligand nalazi u konformaciji stolice. Ispitivane su termogravimetrijske I biološke osobine kompleksa [Co2(Cl)2tpmc](BF4)2 (tpmc = N, N', N'', N'''-tetrakis (2-piridilmetil) -1,4,8,11-tetraazaciklotetradekan). TG-DTA analiza ukazuje da je razlaganje kompleksa u jednom koraku u rasponu temperature od 365 -435 ° C. Ispitivana je citotoksična aktivnost na dve ljudske ćelijske linije karcinoma: HeLa (adenokarcinom grlića maternice) i K562 (mijelogena leukemija). Antimikrobno djelovanje kompleksa kvantifikovano je određivanjem minimalne inhibitorne koncentracije (MIC) korišćenjem bakterija Staphylococcus saprophyticus, Staphylococcus xylosus, Bacillus cereus, soja kvasca Candida albicans i plesni Aspergillus niger. Biološka ispitivanja su pokazala da kompleks ima značajan citotoksični potencijal I umerenu aktivnost prema bakterijama soja Staphylococcus

Uporedni prikaz antimikrobne aktivnosti srodnih Co(II)/Cu(II) kompleksa

The aim of this paper is to compare the efficiency of some analogue of Co (II) and Cu (II) complexes to bacteria pathogenic to humans, which can contaminate vegetables and fruit at any stage of its production. The complexes of Cu(II) and Co(II) with N, N’, N’’, N’’’ - tetrakis (2-pyridylmethyl) -1,4,8,11-tetraazacyclotetradecane (tpmc) and various additional ligands were tested against Gram (+) and Gram (-) bacteria and some strains of fungi. As a control group the free salts of Co(II) and Cu(II) which were used as starting substances in the synthesis, as well as ligands and solvents were tested. The minimum inhibition concentrations suppressing the visible growth of bacteria (MIC) were also screened. Investigated complexes showed a moderate activity against strains of bacteria. Complexes of Co(II) generally showed higher activity then Cu(II) analogues. Under the same conditions and the same concentrations, the control group showed no activity. No compound showed antifungal activity.Cilj ovog rada je poređenje efikasnosti nekih analognih kompleksa Co(II) i Cu(II) na bakterijske vrste patogene za čoveka koje mogu kontaminirati povrće i voće u bilo kojoj fazi njegove proizvodnje. Kompleksi Cu (II) i Co (II) sa N, N’, N’’, N’’’ - tetrakis (2-piridilmetil) -1,4,8,11-tetraazaciklotetradekanom (tpmc) i različitim dodatnim ligandima su testirani na Gram (+) i Gram (-) bakterije i neke sojeve gljiva. Kao kontrolna grupa su testirane i proste soli Co(II) i Cu(II) koje su korišćene kao polazne supstance u sintezi kao i ligandi i rastvarači. Određene su minimalne inhibitorne koncentracije (MIC) koje sprečavaju rast mikroorganizama. Ispitivani kompleksi pokazuju umerenu aktivnost prema sojevima bakterija. Kompleksi Co(II) su pokazali generalno već u aktivnost u odnosu na Cu (II) analoge. Pod istim uslovima i u primenjenim istim koncentracijama kontrolne grupe nisu pokazale aktivnost. Nijedno jedinjenje nije ispoljilo antigljivično dejstvo

Dobijanje i osobine CU(II)kompleksa Sa N,N’,N',N’’’-tetrakis(2-piridilmetil)-1,4,8,11-tetra a za ciklotetradekanom(tpmc)i pseudo halogenidima (NCO- ili NCSe-) - II deo

Two new Cu(II) complexes with N,N’,N",N’’’-tetrakis(2-pyridylmethyl) -1,4,8,11-tetraazacyclotetradecane (tpmc) and pseudohalides (NCO- or NCSe-) were isolated. Elemental analyses (C, H, N, Cu) corresponded to the formulas [Cu2(NCO)tpmc](ClO4)3. 2CH3CN and [Cu2(NCSe)2 tpmc] (ClO4)2. 2H2O. C2H5OH. The coordination mode of tpmc and these ambidentate pseudohalides, geometries spectral characteristics (VIS, IR) and other properties were compared with those of the previously described [Cu2(NCS)2tpmc] (ClO4)2. Antimicrobial activity towards selected bacteria and yeast was tested and found for the NCSe but not the NCO complex.Dobijena su dva nova Cu(II) kompleksa sa N,N’,N’’,N’’’-tetrakis(2-piridilmetil)-1,4,8,11-tetraazacikotetradekanom (tpmc) i pseudohalogenidima (NCO– ili NCSe–). Elementalna analiza (C, H, N Cu) odgovarala je formulama: [Cu2(NCO)tpmc](ClO4)3. 2CH3CN i [Cu2(NCSe)2 tpmc](ClO4)2. 2H2O. C2H5OH. Način koordinacije tpmc-a i ovih ambidentatnih pseudohalogenida, geometrijski raspored, spektralne karakteristike (VIS, IR) i dr. su upoređene sa ranije opisanim [Cu2(NCS)2tpmc](ClO4)2. Antimikrobna aktivnost prema nekim bakterijama i gljivicama je testirana i nađena samo u slučaju NCSe kompleksa

Novi mešovito-ligandni kompleksi Co (II)- sinteza, karakterizacija i antimikrobna aktivnost

A new complexes with general formula [Co2(X)2tpmc](BF4)2·Y (X= F-, Y=CH3CN; X= Br-, Y= H2O; tpmc = N,N',N'',N'''-tetrakis(2-pyridylmethyl)-1,4,8,11-tetraazacyclotetradecane), were isolated and their composition, some of physical and chemical properties and their tentative geometries were evaluated based on: elemental analysis (C, H, N), conductometric and magnetic measurements, spectroscopic data (UV/Vis, IR) respectively. Then, we compared synthesized complexes with early described chloro analogous. Both complexes are binuclear with proposed chair conformation of macrocycle. Complex compounds were also preliminary assayed in vitro toward some Gram (+) and Gram (-) bacteria, fungi and mould together with the starting material for the synthesis (ligands, simple salts and solvents) as test substances. In some cases certain antimicrobial activity of the complexes was detected. Minimal inhibitory concentration suppressing the visible growth of bacteria was determined. Both investigated complexes showed a moderate activity against strains of bacteria and were inactive against the tested fungi and mould. Under the same conditions and applied the same concentration of the control group did not show activity.Pripremlljena su dva nova kompleksa opšte formule [Co2(X)2tpmc](BF4)2·Y (X= F-, Y=CH3CN; X= Br-, Y= H2O; tpmc = N,N',N'',N'''-tetrakis(2-piridilmetil)-1,4,8,11- tetraazaciklotetradekan), čiji su sastav, neke fizičke i hemijske osobine kao i približne geometrije određene na osnovu elementalne analize (C, H, N), konduktometrijskih i magnetnih merenja i spektroskopskih podataka (UV/Vis, IR). Podaci su upoređeni sa ranije sintetisanim i opisanim hloro analogom. Oba nova kompleksa Co(II) su dinuklearna sa pretpostavljenom egzo koordinacijom makrocikla u konformaciji stolice. Kompleksi su preliminarno testirani na neke Gram (+), Gram (-) bakterije, plesni i kvasce zajedno sa startnim supstancama za sintezu (ligandima, prostim solima i rastvaračima) koje su služile kao test supstance. Određivana je minimalna inhibitorna koncentracija koja sprečava rast bakterija. U nekim slučajevima je nađena izvesna antimikrobna aktivnost. Oba kompleksa su pokazala aktivnost prema bakterijama ali su inaktivni prema gljivicama i kvascima dok je pod istim uslovima i istim primenjenim koncentracijama kontrolna grupa bila neaktivna

Design of nanoplatforms for electrochemical sensing of biomolecules

The aim of this study was to investigate thermal behavior of the new complex with formula [Cu(ala)cyc](ClO4)2∙2.5H2O. The complex was isolated and previously characterized by: elemental analysis (C, H, N), molar conductivity, UV/Vis and FTIR spectroscopy and magnetic measurements at room temperature. The sixcoordinate octahedral geometry around Cu(II) complexes was proposed. The experimental data suggested that the tetradentate ligand cyclam was coordinated to metals through four N donors and the amino carboxylate ligand coordinated via carboxylate ion. Investigate of thermal stability can be crucial in confirming the structure as well as in assessing the applicability of new compounds. The thermal properties of these complex have been investigated by thermogravimetric (TG) and differential thermal analysis (DTA). Therefore, TG-DTA analysis indicates that investigated complex decomposes exothermally in a single step in the range of 310 - 400 °C

Synthesis, characterization, and in vitro antiproliferative and antibacterial studies of tetraazamacrocyclic complexes of Co(II) and Cu(II) with pyromellitic acid

AbstrcatNew cationic tetranuclear Co(II) and neutral binuclear Cu(II) complexes with tpmc (N,N,N,N-tetrakis-(2-pyridylmethyl)-1,4,8,11-tetraazacyclotetradecane) and bridging pyromellitate ligand pma (tetraanion 1,2,4,5-benzenetetracarboxylic acid) were isolated. The composition of the compounds is proposed based on elemental analyses (C, H, N, M=Cu, Co), molar conductivity determination, UV-Vis, FTIR, EPR, LC-MS and reflectance spectroscopy, magnetic measurements, cyclic voltammetry, as well as TG and DTA. It is proposed that in [Co-4(pma)(tpmc)(2)](ClO4)(4)6H(2)O (1), cobalt(II) is six-coordinate out of cyclam rings and one OCO- from pma participates in coordination with one Co(II). In the case of [Cu-2(pma)tpmc].8H(2)O (2), one OCO- from pma bridges two Cu(II). The cytotoxic activity of 1 and 2 was tested against tumor cell lines human cervix adenocarcinoma (HeLa), estrogen-receptor-positive human breast cancer (MCF-7), human myelogenous leukemia (K562), and the human Caucasian Burkitt's lymphoma (Ramos). The IC50 values for 1 and 2 were within the range 44.66 +/- 2.39 to 152.40 +/- 2.28M, and from 140.88 +/- 3.51 to 192.05 +/- 2.09M, respectively. Both 1 and 2 were tested for antimicrobial activity. We determined that minimal inhibitory concentration for 1 against Staphylococcus aureus, Bacillus subtilis, and Klebsiella pneumoniae was 25mM. Complex 2 did not express activity against tested microbial strains.This is peer-reviewed version of the following article: Nikolić, M. A.; Stanković, J. A.; Tanasković, S. B. Synthesis, Characterization, and in Vitro Antiproliferative and Antibacterial Studies of Tetraazamacrocyclic Complexes of Co(II) and Cu(II) with Pyromellitic Acid. J. Coord. Chem. 2018, 71 (10), 1542–1559. [https://doi.org/10.1080/00958972.2018.1459581

Spektrofotometrijsko određivanje tioktinske kiseline u vodi i farmaceutskim preparatima

A spectrophotometric method is described for the assay of thioctic acid. The method is based on the reaction between the drug and palladium(II) chloride. In this reaction, a yellow-colored, water soluble product with a 1:1 stoichiometric ratio and an absorption maximum at 365 nm was formed. The stability of the formed complex depends on various factors (pH, reaction time, concentration of reagents, ionic strength). Based on these findings, a new method is suggested for the spectrophotometric determination of thioctic acid in pharmaceutical formulations. This method is simple, sensitive and reproducible.Opisana je jednostavna spektrofotometrijska metoda za brzo i tačno određivanje tioktinske kiseline u vodi, injekcionim rastvorima i tabletama. Spektrofotometrijska merenja su izvođena u Britton-Robinson-ovim puferima pri različitim pH vrednostima (2,00-6,00) i konstantnoj jonskoj sili. Sastav, konstanta stabilnosti, molarna apsorptivnost kompleksa su određene različitim metodama. Utvrđen je 1:1 sastav nagrađenog kompleksa i molarna apsorptivnost 4.2x103 l mol-1 cm-1. Relativna standardna devijacija iznosi od 3,10 do 3,76%,{to odgovara propisanim analitičkim standardima

АНТИОКСИДАТИВЕН КАПАЦИТЕТ И АНТИМИКРОБНИ ЕФЕКТИ НА КОМПЛЕКСИ НА ЦИНК СО ФЛАВОНОИДИ – ДАЛИ ПОСТОИ СИНЕРГИЗАМ?

The presence of residual cardiovascular disease (CVD) risk is a current dilemma in clinical practice; indeed, despite optimal management and treatment, a considerable proportion of patients still undergo major CV events. Novel lipoprotein biomarkers are suggested as possible targets for improving the outcomes of patients at higher risk for CVD, and their impact on major CV events and mortality have previously been investigated. Innovative antidiabetic therapies have recently shown a significant reduction in atherogenic lipoproteins, beyond their effects on glucose parameters; it has also been suggested that such anti-atherogenic effect may represent a valuable mechanistic explanation for the cardiovascular benefit of, at least, some of the novel antidiabetic agents, such as glucagon-like peptide-1 receptor agonists. This emphasizes the need for further research in the field in order to clearly assess the effects of innovative treatments on different novel biomarkers, including atherogenic lipoproteins, such as small dense low-density lipoprotein (LDL), lipoprotein(a) (Lp(a)) and dysfunctional high-density lipoprotein (HDL). The current article discusses the clinical importance of novel lipid biomarkers for better management of patients in order to overcome residual cardiovascular risk.Постои постојана потреба од ефикасни лекови, комбинации на лекови и методи за спречување на бактериски и вирусни инфекции, вклучувајќи го и коронавирусот. Познато е дека улогата на елементи во траги во зајакнување на човековиот имун систем е значајна. Витамините, микроелементите, вклучувајќи цинк, железо, селен, магнезиум и бакар, масните киселини омега-3 играат значајна физиолошка улога во унапредување на имуниот систем. Цинкот е неопходен микроелемент за основните ензимски физиолошки процеси. Тој игра важна улога во делбата на клетките и е вклучен во развојот на клетки одговорни за неспецифичен имунитет. Познато е дека недостигот на цинк ги предиспонира пациентите на вирусни инфекции поради намалениот антивирусен имунитет. Од друга страна, флавоноидите како метаболити на растенијата играат важна улога во спречување на оксидативен стрес. Овој труд има за цел да ја дискутира in vitro улогата на цинкот, флавонидите и нивните комплекси, како и нивните антиоксидативни и антимикорбни активности. Разгледана е и оправданоста за истовремена употреба на цинк и флавоноиди

A study of novel cobalt(II) octaazamacrocyclic complexes with aminocarboxylates or their derivativ

Four new air-stable mixed-ligand Co(II) complexes having the general formula [Co2(Y)tpmc]Z3×q(H2O/CH3CN) (HY = N-methylglycine/N,N-dimethylglycine, Z = BF4-, qH2O = 4 or 3; HY = S-norvaline/S-valine Z = ClO4- , qCH3CN = 0.5; qH2O = 0.5; tpmc = N,N’,N’’,N’’’-tetrakis(2-pyridylmethyl)-1,4,8,11-tetraazacyclotetradecane) were prepared. The composition, some physical and chemical properties and their tentative geometries were evaluated based on elemental analysis (C, H, N), conductometric and magnetic measurements, spectroscopic data (UV/Vis, IR) and cyclic voltammetry. The data were compared with earlier described analogous complexes containing the macrocyclic ligand and aliphatic aminocarboxylates. It is assumed that all complexes are binuclear with an exo coordination mode of the octaazamacrocyclic pendant ligand in the boat conformation. In addition, two –N–(CH2)2–N– portions of the cyclam ring within the tpmc ligand and Co(II) ions in the high-spin state are most probably bridged via oxygen atoms from the anion of the amino-carboxylate/derivatives, whereas nitrogen atoms rest uncoordinated. In all cases, a combined chelate-bridged coordination is proposed as the most probable. The complexes were electrochemically stable in the potential range –1.0 to 1.0 V. They were also preliminary assayed toward some microorganisms together with the ligands, starting simple salts and solvents as test substances. In some cases, certain antimicrobial activity of the complexes was detected

Nови мешовитолигандни макроциклични комплекси Ni(II) и Zn(II) са мостовним (endo,endo)-бицикло-[2.2.1]-хепт-5-ен-2,3-дикарбоксилатом: синтеза, карактеризација, антимикробна и цитотоксична активност

New carboxylate complexes of the tetraazamacrocyclic ligand N,N',N'',N'''-tetrakis(2-pyridilmethyl)-1,4,8,11-tetraazacyclotetradecane (tpmc) with Ni(II) and Zn(II) as central ions were prepared. In mixed-ligand com- plexes (endo,endo)-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate dianion (C9H8O42- ) is also coordinated to metal ions. The complexes were characterized by ele- mental analysis (C, H, N), FTIR and UV–Vis spectroscopy, molar conductivity determination and magnetic susceptibility measurement at room temperature. The analytical data of the complexes show the formation of binuclear [Ni2(C9H8O4)tpmc](ClO4)2·4H2O and tetranuclear [Zn4(C9H8O4)(tpmc)2](ClO4)6· ·CH3CN·KClO 4·4H2O complexes. In tetranuclear Zn(II) complex bicyclic dicarboxylate ligand is most likely to be bridge coordinated, and in binuclear Ni(II) complex it is coordinated in a combined bridged manner with chelate rings formation. In both complexes macrocyclic ligand was exo coordinated, out of cyclam ring and adopts a boat conformation. The Zn(II) complex is one of the rare tetranuclear Zn(II)-tpmc complexes with carboxylate ion bridging two Zn2tpmc units. The complexes were tested for antibacterial activity against Gram-positive bacteria Staphylococcus aureus (ATCC 25923) and Bacillus subtilis (ATCC 6633), Gram-negative bacterium Escherichia coli (ATCC 25922), and yeast Candida albicans (ATCC 10231), and were screened for antiproliferative activity against human cervix adenocarcinoma (HeLa) and human myelogenous leukemia (K562) cell lines.Синтетисани су нови карбоксилато комплекси са тетраазамакроцикличним ли- гандом N,N',N'',N'''-тетракис(2-пиридилметил)-1,4,8,11-тетраазациклотетрадеканом (tpmc) и Ni(II) и Zn(II) као централним јонима. У мешовитолигандним комплексима (endo,endo)-бицикло-[2.2.1]-хепт-5-ен-2,3-дикарбоксилато дианјон (C9H8O4 2- ) је такође везан за метални јон. Комплекси су окарактерисани елементалном анализом (C, H, N), FTIR и UV/Vis спектроскопијом, као и мерењем моларне проводљивости и магнетне сусцептибилности на собној температури. На основу добијених резултата претпос- тављена је бинуклеарна структура [Ni2(C9H8O4)tpmc](ClO4) 2·4H2O комплекса, односно, тетрануклеарна [Zn4(C9H8O4 )(tpmc) 2](ClO4)6·CH3CN·KClO4 ·4H2O комплекса. У тетра- нуклеарном Zn(II) комплексу, бициклични дикарбоксилато лиганд је највероватније мостно везан, док је у бинуклеарном Ni(II) комплексу мешовити мостно-хелатни начин координације. Други начини мостног везивања дикарбоксилата не могу бити у потпуности искључени. У оба комплекса макроциклични лиганд је егзо координован, изван цикламовог прстена и заузима конформацију лађе. Добијени Zn(II) кoмплекс је један од ретких тетрануклеарних Zn(II)–tpmc комплекса са карбоксилато лигандом у мосту између две Zn2tpmc јединице. Добијени комплекси су тестирани на антибактеријску активност према Грам-позитивним бактеријама Staphylococcus aureus (ATCC 25923) и Bacillus subtilis (ATCC 6633), Грам-негативној бактерији Escherichia coli (ATCC 25922) и квасцу Candida albicans (ATCC 10231). Испитивана је њихова антипролиферативна активност на хуманим малигним ћелијским линијама: цервикалног аденокарцинома (HeLa) и мијелогене леукемије (K562)