Mechanism of change in enantiomer migration order of enantioseparation of tartaric acid by ligand exchange capillary electrophoresis with Cu(II) and Ni(II)-D-quinic acid systems

The mechanism of change in the enantiomer migration order (EMO) of tartarate on ligand exchange CE with Cu(II)- and Ni(II)-D-quinic acid systems was investigated thoroughly by circular dichroism (CD) spectropolarimetry. The (13) C NMR spectra of solutions containing D-quinate (pH 5.0) with Cu(II) or Ni(II) revealed the coordination of carboxylate and hydroxyl groups on D-quinate. The D-quinic acid concentration dependence of the CD spectra at a fixed Cu(II) concentration at pH 5.0 indicates that the 1:1, 1:2 and 1:3 Cu(II)-D-quinate complexes were formed with an increase in the concentration of D-quinic acid. The CD spectral behavior revealed that D-tartarate is selectively coordinated to the 1:1 complex to give the 1:1:1 Cu(II)-D-quinate-D-tartarate ternary complex while L-tartarate is selectively bound to the 1:2 and 1:3 complexes to form the 1:2:1 ternary complex. In the Ni(II)-D-quinic acid system, it became apparent that the 1:2 Ni(II)-D-quinate complex is mainly formed in the wide range of D-quinic acid concentration at pH 5.0 and D-tartarate is selectively coordinated to the 1:2 complex to form the 1:2:1 ternary complex. The change in EMO of tartarate on ligand exchange CE was explainable by the change in coordination selectivity for D- and L-tartarates in the Cu(II)- and Ni(II)-D-quinic acid systems depending on the compositions of the complexes formed in BGE.     

Adsorption behavior of copper and cyanide ions at TiO2-solution interface

Adsorption of both copper and cyanide ions in the absence and in the presence of their complexes at TiO2-solution interfaces was investigated. The objective of this study was to demonstrate the possibility of removing heavy metal ions, exemplified by Cu(II), from aqueous solution in the presence of a ligand, e.g., CN-. Several parameters such as pH and Cu(II) and CH- ion concentration that may affect the magnitude of copper and cyanide adsorption were studied. The equilibrium of Cu-CN speciation distribution in solution and stability constant calculations have been investigated to determine the adsorption behavior of Cu(II). Results revealed that free Cu(II) ions (in the absence of CN-) were completely separated at pH8, while the adsorption of free cyanide ions, in the absence of Cu(II), reached a maximum value of 48% at pH 7. For Cu-CN complexes, the presence of CN- in excessive amount with respect to Cu(II) retarded the adsorption of Cu(II). This is attributed to the formation of multivalent anionic cyano-copper complexes such as Cu(CN)2-(3) and Cu(CN)(3-)4.     

Cadmium(II) and copper(II) complexes with imidazole-containing tripodal polyamine ligands: pH and anion effects on carbon dioxide fixation and assembling

A new Cd(II) complex [Cd3(L)3(mu3-CO3)](ClO4)4.2CH3CN (1) with two-dimensional (2D) network structure was obtained by reaction of an imidazole-containing tripodal polyamine ligand N1-(2-aminoethyl)-N1-(2-imidazolethyl)-ethane-1,2-diamine (L) with Cd(ClO4)2.6H2O at pH 9.0 in air. The carbonate anions (CO3(2-)) are from the hydration of the atmospheric carbon dioxide, which is the same as in the previously reported Cu(II) complex [Cu3(L)3(mu3-CO3)](ClO4)4.3CH3CN (2). However, the coordination mode of CO3(2-) in 1 is mu3-eta2:eta2:eta2 while the one in 2 is mu3-eta1:eta1:eta1. One-dimensional (1D) chain Cd(II) and Cu(II) complexes [Cd(L)Cl]ClO4.H2O (3) and [Cu(L)(H2O)](ClO4)2 (4) without CO3(2-) were prepared by a similar method as that for 1 and 2 except for the different reaction pH, namely, 3 and 4 were obtained at pH 7 while 1 and 2 were obtained at pH 9. In addition, when Cu(NO3)2 was used to react with L at pH 9, a unique 1D double-stranded helical chain complex [Cu(L)Cl]NO3.1.25H2O (5) was obtained. The results revealed that the reaction pH and the counteranion have great impact on the carbon dioxide absorption and hydration as well as on the assembling and structure of the complexes. The magnetic property of complex 2 was investigated in the temperature range of 1.8-300 K, and weak ferromagnetic coupling among the mu3-eta1:eta1:eta1-CO3(2-) bridged Cu(II) atoms was observed.     

Study of binary complexes of Cu(II), Ni(II) and Co(II) with sulfamethazine by voltammetry

Cyclic voltammetry (CV) and square-wave voltammetry (SWV) techniques have been used to study the binary complexes of Co(II), Ni(II) and Cu(II) with sulfamethazine (SMZ) at a static mercury drop electrode (SMDE) in 0.04 M Britton-Robinson (B-R) buffer. SMZ gave three peaks at 0.01, −1.32 and −1.55 V. Cu(II)-SMZ complex was recognized by a cathodic peak at −0.38 V. Ni(II)-SMZ complex was reduced at more positive potential (−0.77 V) than that of the hydrated Ni(II) ions (−1.08 V). Co(II)-SMZ complex is investigated at pH 7 and 8. The Co(II) complex at pH 7 is appeared as a shoulder at −1.19 V, whereas this peak becomes a well-separated form at pH 8. The study indicated that the SMZ serves as a catalyst in the reduction of Co(II) and Ni(II) ions. From electronic spectra data of the complexes, their stoichiometries of 1: 2 (metal-ligand) in aqueous medium are determined. The stability constants of the complexes are in agreement with the Irwing-Williams series (Co < Ni < Cu).     

Investigation of complexes tannic acid and myricetin with Fe(III)

The pH dependence of the complexes was determined by both potentiometric and spectrophotometric studies. Stability constants and stoichiometries of the formed complexes were determined using slope ratio method. Fe(III) was formed complexes with tannic acid of various stoichiometries, which in the 1:1 molar ratio at pH<3, in the 2:1 molar ratio at pH 3-7 and in the 4:1 molar ratio at pH>7. Fe(III) was formed complexes with myricetin in the 1:2 molar ratio at pH 4 and 5 and in the 1:1 molar ratio at pH 6. Stability constant values were found to be 10(5) to 10(17) and 10(5) to 10(9) for Fe(III)-tannic acid complexes and Fe(III)-myricetin complexes. Both tannic acid and myricetin were possessed minimum affinities to Cu(II) and Zn(II). They had less affinity for Al(III) than for Fe(III).     

Selectrode--the universal ion-selective electrode-V. Complex formation studies with the Cu(II) Selectrode

The Cu(II) Selectrode, calibrated in a series of Cu(II) buffers at various pH levels, has been used for the determination of the stability constants of the Cu(II) complexes of glycine and EGTA at an ionic strength of 0.1. Methods for the calculation of the stability constants of chelate complexes from pH and pM values are presented. The values obtained compare very favourably with those recorded in the literature. For the Cu(II)-EGTA system, for which only a few stability constants have been determined, the following constants were found: logK(Cu, L)(CuL) = 16.80; logK(H, CuL)(CuHL) = 5.30; logK(2H, CuL)(CuH2L) = 7.64; logK(H, CuHL)(CuH2L) = 2.34; logK(Cu, HL)(CuHL) = 12.56; and logK(Cu, H2L)(CuH2L) = 5.97. Examples of the application of the Cu(II) Selectrode in replacement reactions are illustrated.     

Characterization of Ni(II) and Cu(II) complexes of 4-(2-Quinolylmethyleneamino)-1-phenyl-2,3-dimethyl-5-pyrazolone and their analytical applications

A synthesis of the new reagent 4-(2-quinolylmethyleneamino)-1-phenyl-2,3-dimethyl-5-pyrazolone (QPP) and of its complexes with Ni(II) and Cu(II) is described. The structure of the ligand itself and the nature of the bonding in complex molecules were determined by elemental analysis, IR, and mass spectrometry. The analysis of data showed that isolated crystal metal complexes are of the ML₂ type. The composition and stability constants of the complexes in water/methanol solutions, (methanol) = 0.16, at constant temperature 25 ±1 °C and ionic strength of 0.5 M (KNO₃) at different pH (4, 6, 8, and 10) have been determined spectrophotometrically. The results indicate that the metal complexes formed in the solution have a metal-to-ligand ratio 1:2. The reaction of QPP with Ni(II) and Cu(II) in solution was quantitatively studied. The lowest detection limit for the determination of Ni is 0.3 μg/ml while that for Cu is 0.05 μg/ml under the investigated experimental Conditions.     

2,6-di(pyrimidin-4-yl)pyridine ligands with nitrogen-containing auxiliaries: the formation of functionalized molecular clefts upon metal coordination

A series of ligands (1-4) based on a 2,6-di(pyrimidin-4-yl)pyridine scaffold have been synthesized, and their abilities to form complexes with Zn(II) and Cu(II) have been determined using UV/vis spectroscopy in buffered aqueous solution (0.01 M N-[2-hydroxyethyl]piperazine-N'-[3-ethanesulfonic acid] (HEPES) at pH = 6.8). The Zn(II) complex of 1 was determined to have a formation constant of 8.4 x 10(3) M(-)(1) while the formation constant of the Cu(II) complex was found to be 1 x 10(6) M(-)(1). The presence of auxiliary amines in 2 increased the stability of the Zn(II) complex relative to that of 1 by a factor of over 40, suggesting possible coordination of the auxiliaries to the Zn(II) center. The guanidinium and 2-amino-4,5-dihydro-imidazolinium groups of 3 and 4 considerably diminished the stability of the Zn(II) and Cu(II) complexes relative to those of 1. X-ray crystal structures of 1-Zn, 3-Zn, 4, and 4-Zn were obtained and are discussed. A significant increase in the stability of 3-Zn, but not in the stability 1-Zn, was observed upon the addition of 1 equiv of sodium phosphate, implicating a stabilizing interaction of the guanidinium groups of 3-Zn and the phosphate anion.     

Colorimetric recognition of Cu(II) by (2-dimethylaminoethyl)amino appended anthracene-9,10-diones in aqueous solutions: deprotonation of aryl amine NH responsible for colour changes

Chromogenic receptors 2 and 3 undergo distinct colour changes from magenta to blue on gradual addition of Cu(II) and can be used as colorimetric probes for spectrophotometric and visual analysis of Cu(II) in the presence of biological metal ions Na(I), K(I), Mg(II), Ca(II), Fe(II), Zn(II) etc. in aqueous solution (methanol-water 1 : 1 v/v). On addition of Cu(II), both 2 and 3 exhibit a bathochromic shift of Delta lambda(max) = 114 nm for 2 and Delta lambda(max)= 150 and 265 nm for receptor 3. The protonation constants and formation constants of Cu(II) complexes of receptors 2 and 3 (at pH 7) and the effect of pH on formation of these complexes has been determined by the combination of UV-vis-pH titrations of receptors 2 and 3 and their Cu(II) complexes. These results and the emergence of only one peak at 610 nm for 2 and two distinct absorption peaks at 715 and 800 nm for 3 on addition of Cu(II) unambiguously point to mono- and di-deprotonation for 2 and 3, respectively.     

Spectrophotometric Study of Mithramycin Complexes with Cu(II), Fe(III) and Tb(III)

Abstract

The coordination of the anticancer drug mithramycin to Tb(III), Fe(III) and Cu(II) was studied in aqueous solution using absorption measurements. The stability constants were calculated from equilibrium competition experiments by means of the SQUAD program. For both first ions, the competitor was oxalic acid and for the latter the competitor was the Cu(II) ions. Cu(II) at pH 7.5, Fe(III) at pH 3.5 and Tb(III) at pH 5.5 formed respectively 1:2, 1:3 and 1:4 metal-to-ligand species.     

配位化学中的直线自由能关系XXI: 铜(II)-13-取代苄基-1, 4, 8, 11-四氮杂环十四烷-12, 14-二酮配合物的生成及酸分解行为研究

采用pH法, 在25.0±0.1℃, I=0.1 mol.dm^-^3 (KNO3)条件下, 测定了13-取代苄基-1, 4, 8, 11-四氮杂环十四烷-12,14-二酮的质子化常数及其与Cu(II)配位的平衡常数。讨论了配体与金属离子的配位方式。在25.0±0.1℃, 离子强度为0.1mol.dm^-^3 (KNO3)下, 采用分光光度法, 研究了这些配体铜(II)配合物的酸分解动力学行为。探讨了配合物酸分解机理,得到了速控步的速率常数。发现配位反应平衡常数与配体的质子化常数及配合物酸分解反应速率常数之间存在较好的Hammett型和Bronsted型直线自由能关系。同时探讨了取代基对配合物生成及酸分解的影响情况。     

Spectrophotometric determination of stability constants of Ni(II) and Cu(II) complexes with N-substituted hydrazinedithiocarboxylic acids

The stability constants of Ni(II) complexes with 2-methylhydrazinedithio-carboxylic and 3,3-dimethylhydrazinedithiocarboxylic acids and Ni(II) and Cu(II) complexes with 3-methyl-3-phenylhydrazinedithiocarboxylic acid have been determined in aqueous solution at 25°C and I = 0.01 M. The Bjerrum method of corresponding solutions has been applied, revealing the simultaneous presence of 1:1 and 1:2 complexes in solution.     

Spectrophotometric study of etodolac complexes with copper (II) and iron (III)

A rapid, simple, and selective method was developed for the determination of etodolac. The method depends on complexation of etodolac with copper (II) acetate and iron (III) chloride followed by extraction of complexes with dichloromethane and then measuring the extracted complexes spectrophotometrically at 684 and 385 nm in case of Cu (II) or Fe (III), respectively. Different factors affecting the reaction, such as pH, reagent concentration, and time, were studied. By use of Job's method of continuous variation, the molar ratio method, and elemental analysis, the stoichiometry of the reaction was found to be in the ratio of 1:2 and 1:3, metal:drug in the case of Cu (II) and Fe (III), respectively. The method obeys Beer's law in a concentration range of 2.00-9.00 and 0.50-2.00 mg/mL in case of Cu (II) and Fe (III), respectively. The stability of the complexes formed was also studied, and the reaction products were isolated for further investigation. The complexes have apparent molar absorptivities of about 32.14 +/- 0.97 and 168.32 +/- 1.12 for Cu (II) and Fe (III), respectively. The suggested procedures were successfully applied to the analysis of pure etodolac and its pharmaceutical formulations. The validity of the procedures was further ascertained by the method of standard additions, and the results were compared with other reported spectrophotometric methods and showed no significant difference in accuracy and precision.     

Binary and ternary complexes of Cu(II) ions with saccharin and cysteine

The square-wave voltammetric behaviour of cysteine and saccharin was studied at a static mercury drop electrode at pH 7.4 in the presence of Cu(II) ions. In the presence of excess Cu(II), cysteine exhibited three reduction peaks for Hg(SR)₂ (−0.086 V), free Cu(II) (−0.190 V) and Cu(I)SR (−0.698 V), respectively. Saccharin produced a catalytic hydrogen peak at −1.762 V. In the presence of Cu(II), saccharin gave a new peak (−0.508 V), corresponding to the reduction of Cu(II)–saccharinate, which in the presence of cysteine formed a mixed ligand complex (−0.612 V), CuL₂A₂ (L=saccharin and A=cysteine). The peak potentials and currents of the obtained complexes were dependent on the ligand concentration and accumulation time. The stoichiometries and overall stability constants of these complexes were determined by Lingane's method (voltammetrically) and Job’s method (spectrophotometrically). The mixed ligand complex in the molar ratio 1:2:2 (log β=33.35) turned out to be very much stronger than the 1:1 Cu(I)SR (log β=21.64) and 1:2 Cu(II)–saccharinate (log β=16.68) complexes. Formation of a mixed ligand complex can be considered as a type of synergism.     

Synthesis, physico-chemical and DNA interaction studies of homo- and hetero-trinuclear complexes

Synthesis and characterization of three new trinuclear metal complexes of type Cu3, Cu2Zn and Cu2Ni have been achieved by assembling simple mononuclear complexes, namely 2,2'-bipyridyl 3,4-dihydroxo benzaldehyde copper(II) complex and diethylenetriamine complexes of copper(II), nickel(II) and zinc(II) ions, through the reaction of coordinated ligands. The FAB mass spectra for the complexes show fragmentation pattern in accordance with the molecular formula. The frozen electron paramagnetic resonance (EPR) spectrum of tricopper complex shows two sets of parallel lines with approximately 2:1 ratio. The simulation has been carried out by considering dipolar interaction between the two types of copper ions present in the complex. The trimetallic complexes, Cu3, Cu2Ni and Cu2Zn show strong intercalation type of interaction with Calf thymus DNA in 0.02 mol L(-1) of phosphate buffer containing 60 mmol sodium chloride at pH 7.0 at room temperature. The binding constant is found to be in the order Cu3相似文献   

Investigation of ketoconazole copper(II) and cobalt(II) complexes and their spectrophotometric applications

Ketoconazole, as a ligand, reacts quantitatively with copper(II) and cobalt(II) to form blue-colored, stable complexes in dichloromethane. These complexes can be spectrophotometrically measured at 720 and 612.5 nm in the case of Cu(II) or Co(II), respectively. Different factors affecting the reaction such as pH, reagent concentration, solvent effect, and time were studied. By using Job's method of continuous variation, the stoichiometry of the reaction was found to be in the ratio of 1:2, metal:drug, with Cu(II) and Co(II). The stability of the complexes formed was also studied. The reaction products were isolated for further investigation. The complexes have apparent molar absorptivities of 35.36 +/- 1.95 and 59.62 +/- 1.87 for Cu(II) and Co(II), respectively. Suggested procedures based on the stoichiometric reaction were successfully applied to the analysis of the pure drug and its pharmaceutical formulations. The validity of the procedures was further ascertained by the method of standard additions. The developed method was found to be simple, accurate, and precise when compared with the official method of the British Pharmacopoeia.     

Solution chemistry of copper(II)-gentamicin complexes: relevance to metal-related aminoglycoside toxicity

The adverse effect to the inner ear of aminoglycosides, drugs widely administered for the treatment of serious infections, appears to result from the interaction of these drugs with Cu(II) or Fe(II)/Fe(III) ions. To understand more completely the metal-induced side effects of one such antibiotic, gentamicin, we studied copper(II) coordination to gentamicin C1a by potentiometry, UV-vis, CD, and EPR spectroscopies, and ESI mass spectrometry. Only monomeric complexes of the CuH(n)L stoichiometry, with n ranging from 3 to -2, were detected over the pH range of 4-12. CuH(3)L and CuH(2)L complexes exhibit the same coordination mode, binding copper(II) through the amino nitrogen atom and a deprotonated alcoholic oxygen atom of the garosamine ring. In the CuHL and CuL complexes a second amino nitrogen atom of the purpurosamine ring participates in central ion coordination. Finally, the additional axial binding of the deprotonated oxygen of the hydroxyl group of the 2-deoxystreptamine moiety occurs in the CuH(-)(1)L and CuH(-)(2)L complexes. Interactions of the Cu(II)-gentamicin-H(2)O(2) system at pH 7.4 with N,N-dimethyl-p-nitrosoaniline, arachidonic acid, and plasmid DNA confirmed that gentamicin complexes facilitate oxidative reactions leading to peroxidation of arachidonic acid and scission of double-stranded DNA mediated by copper-bound reactive oxygen species. However, the stability constants of Cu(II)-gentamicin complexes are inferior to the binding constants of copper(II) complexes with other components of human serum or cells. Computer simulations of copper(II) distribution in the human blood plasma showed that the concentration of gentamicin would have to be at impossible levels (100 M) before a significant fraction of Cu(II) ions would be bound to gentamicin. Further, once introduced into aqueous solution, histidine replaces gentamicin in Cu(II)-gentamicin complexes. Therefore, Cu(II)-gentamicin complexes might not exist under physiological conditions.     

Structure-activity studies on the cleavage of an RNA analogue by a potent dinuclear metal ion catalyst: effect of changing the metal ion

Dinuclear Cd(II), Cu(II), and Zn(II) complexes of L2OH (L2OH = 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane) are compared as catalysts for cleavage of the RNA analogue HpPNP (HpPNP = 2-hydroxypropyl 4-nitrophenyl phosphate) at 25 degrees C, I = 0.10 M (NaNO(3)). Zn(II) and Cu(II) readily form dinuclear complexes at millimolar concentrations and a 2:1 ratio of metal ion to L2OH at neutral pH. The dinuclear Zn(2)(L2O) and Cu(2)(L2O) complexes have a bridging alkoxide group that brings together the two cations in close proximity to facilitate cooperative catalysis. Under similar conditions, the dinuclear complex of Cd(II) is a minor species in solution; only at high pH values (pH 10.4) does the Cd(2)(L2O) complex become the predominant species in solution. Analysis of the second-order rate constants for cleavage of HpPNP by Zn(2)(L2O) is straightforward because a linear dependence of pseudo-first-order rate constant on dinuclear complex is observed over a wide pH range. In contrast, plots of pseudo-first-order rate constants for cleavage of HpPNP by solutions containing a 2:1 ratio of Cd(II) to L2OH as a function of increasing L2OH are curved, and second-order rate constants are obtained by fitting the kinetic data to an equation for the formation of the dinuclear Cd(II) complex as a function of pH and [L2OH]. Second-order rate constants for cleavage of HpPNP by these dinuclear complexes at pH 9.3 and 25 degrees C vary by 3 orders of magnitude in the order Cd(2)(L2O) (2.8 M(-)(1) s(-)(1)) > Zn(2)(L2O) (0.68 M(-)(1) s(-)(1)) > Cu(2)(L2O) (0.0041 M(-1) s(-1)). The relative reactivity of these complexes is discussed in terms of the different geometric preferences and Lewis acidity of the dinuclear Zn(II), Cu(II), and Cd(II) complexes, giving insight into the importance of these catalyst properties in the cleavage of phosphate diesters resembling RNA.     

Polarographic investigation of Cu(II) complexes with N,N,N',N'-tetrakis-(2-hydroxypropyl)-ethylenediamine

During investigation of the formation of Cu(2+) ion complexes with N,N,N',N'-tetrakis-(2-hydroxypropyl)-ethylenediamine (Quadrol-Q) by means of constant current polarography (20 degrees C, ionic strength J = 3 mol l(-1)), the possibility of the formation of two complex compounds; CuQ(2+) and CuQ(2+)(2), was shown within the pH range from 6 to 8. The logarithms of the stability constants for these compounds are 10.6 +/- 0.5 and 14.6 +/- 0.4 respectively. Cu(II) complexation increases sharply when the pH increases from 8 to 10. It was shown that the data at a pH of greater than 10 are in accordance with the existence of the hydroxy complexes CuQ(OH)(2) and CuQ(2)(OH)(2), the logarithms of the stability constants being 26.9 +/- 0.5 and 29.1 +/- 0.3.     

Complex Formation Reactions of Promethazine Copper(II) and Various Biologically Relevant Ligands. Synthesis,Equilibrium Constants,Spectroscopic Characterization and Biological Activity

Binary and ternary complexes of copper(II) involving promethazine, N,N-dimethyl-3-(phenothiazin-10-yl)propylamine (Prom) and various biologically relevant ligands containing different functional groups, were investigated. The ligands (L) are dicarboxylic acids, amino acids, amides and DNA constituents. The ternary complexes of amino acids, dicarboxylic acids or amides are formed by simultaneous reactions. The results showed the formation of Cu(Prom)(L) complexes with amino acids and dicarboxylic acids. The effect of chelate ring size of the dicarboxylic acid complexes on their stability constants was examined. Amides form both Cu(Prom)(L) complexes and the corresponding deprotonated species Cu(Prom)(LH₋₁). The ternary complexes of copper(II) with (Prom) and DNA are formed in a stepwise process, whereby binding of copper(II) to (Prom) is followed by ligation of the DNA components. DNA constituents form both 1:1 and 1:2 complexes with Cu(Prom)²⁺. The stability of these ternary complexes was quantitatively compared with their corresponding binary complexes in terms of the parameters Δlog₁₀ K. The values of Δlog₁₀ K indicate that the ternary complexes containing aromatic amino acids were significantly more stable than the complexes containing alkyl- and hydroxyalkyl-substituted amino acids. The concentration distribution of various complex species formed in solution was also evaluated as a function of pH. The solid complexes [Cu(Prom)L)] where L=1,1-cyclobutanedicarboxylic acid (CBDCA), oxalic and malonic acid were isolated and characterized by elemental analysis, infrared, TGA, and magnetic susceptibility measurements. Spectroscopic studies of the complexes revealed that the complexes exhibits square planar coordination with copper(II). The isolated solid complexes have been screened for their antimicrobial activities using the disc diffusion method against some selected bacteria and fungi. The activity data show that the metal complexes are found to have antibacterial and antifungal activity.