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1.
The Ca2+ indicator 7-chlorotetracycline has been shown to bind to a pore complex on both outer surfaces of all non-meristematic cells in the unistratose thallus of Riella (chlorotetracycline-binding surface region=CSR; Grotha, 1983, Planta 158, 473–481). Prolonged treatment of the thallus with 7-chlorotetracycline, 5-hydroxytetracycline, verapamil and desmethoxyverapamil induces the deposition of callose at the same region. The influence of various treatments on verapamil-induced CSR-callose was measured in situ by microfluorometry of aniline-blue-stained material. Callose deposition is maximal at 10-4M verapamil or 5·10-5M desmethoxyverapamil with 2·10-4M Ca2+ or Mg2+ in the medium. The reaction is completely inhibited at pH 5.5 and is optimal between pH 6.5 and 7.5. The production of CSR-callose is absolutely light-dependent with callose being first visible after 30 min of light. La3+, ethylene glycol-bis(-aminoethylether)-N,N,N,N-tetraacetic acid and amiprophosmethyl, antagonists of Ca2+ functions, and 2-deoxy-D-glucose suppress the verapamil induction of CSR-callose. Furthermore the ionophores A 23187, valinomycin and monensin effectively block the reaction. The deposition of CSR-callose is diminished at increasing external osmolarity and is abolished at osmotic values that stimulate plasmolysis-callose. Wounding causes the formation of wound-callose but inhibits the induction of CSR-callose in cells of the wound edge. Nifedipine increases or prolongs callose synthesis in cell plates. The Ca2+-channel blocker diltiazem is completely ineffective. It is suggested as a working hypothesis that verapamil-induced CSR-callose synthesis is caused by a local change in membrane permeability, possibly as a consequence of the opening of Ca2+ channels being involved in Golgi-vesicle mediated exocytosis (A. Kramer and H. Lehmann, 1986, Ber. Dtsch. Bot. Ges. 99, 111–121).Abbreviations APM
amiprophosmethyl
- APW
artificial pond water
- CSR
chlorotetracycline-binding surface region
- CTC
7-chlorotetracycline
- DDG
2-deoxy-D-glucose
- EGTA
ethylone glycol-bis(2-aminoethylether)-N,N,N,N-tetraacetic acid
- OTC
5-hydroxytetracycline
- Pipes
1,4-piperazinediethane sulfonic acid
Dedicated to Professor Luise Stange on the occasion of her 60th birthday 相似文献
2.
Interactions of tetracycline and its derivatives with DNA in vitro in presence of metal ions 总被引:3,自引:0,他引:3
The interactions of calf thymus DNA with tetracycline (TC), 7-chlorotetracycline (CTC) and 6-dimethyl-7-chlorotetracycline (DMTC) were assessed employing spectrofluorometric and circular dichroism (CD) techniques. The Scatchard analysis revealed relatively lesser binding affinity of TC (Ka= 1.2 x 10(7) lmol(-1)) vis-a-vis CTC (Ka= 3.4 x 10(7) lmol(-1)) and DMTC (Ka= 3.0 x 10(7) lmol(-1)) with DNA. The data suggested both the intercalative and electrostatic nature of binding between the tetracyclines and DNA. The presence of Cu(II) augmented the interaction of tetracyclines with DNA, and resulted in red shift by 12 nm in CD spectra of tetracycline. The molar ellipticity (theta) also changed significantly for CTC and DMTC. The data unequivocally demonstrated the DNA binding potential of tetracyclines both in the presence and absence of Cu(II) ions in dark. The enhanced binding of tetracyclines in presence of Cu(II), ensuing conformational changes in DNA secondary structure to a varying extent, reflects differential reactivity of ligand chromophores. 相似文献
3.
Seven of eight strains of Mycoplasma (PPLO) were found to be sensitive to the deoxystreptamines, certain macrolides, and the tetracyclines. These antibiotics are relative noncytotoxic. Kanamycin and tetracycline were useful in eliminating PPLO (pleuropneumonia-like organisms) strain Squibb no. 1 from a HeLa cell line which was deliberately contaminated with PPLO. Repeated exposure of M. laidlawii type B cells to neomycin resulted in a 50-fold increase in resistance, and the resistant strain was also resistant to gentamicin, kanamycin, neomycin, and paromomycin. A tetracycline-resistant strain of this culture was found to be resistant to 7-chlortetracycline, 7-chlor-6-demethyltetracycline, and 5-hydroxytetracycline. One PPLO strain, Squibb no. 2, derived from a contaminated HeLa cell culture, was resistant to all antibiotics studied. 相似文献
4.
An analytical method for determining very high binding constants at equilibrium for reactions requiring an effector is proposed and applied to study the interaction of tetracycline with the repressor of the tetracycline resistance gene from Tn10. In this method complex formation is limited by low concentrations of the effector, which is Mg2+ for the interaction of tetracycline and Tet repressor. The binding of Mg2+ to tetracycline and subsequent formation of the ternary repressor-Mg(2+)-tetracycline complex are coupled reactions yielding a dependence of repressor-tetracycline-Mg2+ complex formation on the concentration of free Mg2+. The binding constants can be determined from the quantitative analysis of ternary complex formation with increasing Mg2+ concentrations. This method allows the determination of very high association constants at equilibrium in a large range of protein concentrations. In the case of repressor and tetracycline, the same affinity constant of 3 +/- 2 x 10(9) M-1 was found in the range of 0.1 to 5 microM of repressor. This result indicates that no association or dissociation of the repressor subunits occurs upon binding of tetracycline. Furthermore, the results show that a repressor dimer binds two effector molecules without significant cooperativity. 相似文献
5.
The complexation of glutathione and related ligands by the nitrilotriacetic acid complex of Cd2+ (Cd(NTA)-) has been investigated by 1H NMR as a model for the coordination chemistry of Cd2+ and GSH in biological systems. Related ligands included glycine, glutamic acid, cysteine, N-acetylcysteine, penicillamine, N-acetylpenicillamine, mercaptosuccinic acid, and the S-methyl derivative of glutathione. The nature of the complexes formed was deduced from 1H NMR spectra of Cd(NTA)- and the ligands. Mixed ligand complexes (Cd(NTA)L) and single ligand complexes (CdLx) are formed with the thiol ligands, whereas only mixed ligand complexes form with glycine, glutamic acid and S-methylglutathione. Formation constants of the mixed and the single ligand complexes were determined from NMR data. The results indicate that formation constants for binding of a thiolate donor group by Cd2+, either as the free ion or in a coordinately unsaturated complex, are in the range 10(5)-10(6). 相似文献
6.
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8.
W L Baker 《Archives of biochemistry and biophysics》1987,252(2):451-457
Copper-catalyzed oxidation of ascorbic acid was retarded in the presence of the biological disulfide compounds cystine and oxidized glutathione. The evidence suggested that this effect was due to the formation of a stable complex involving the copper ion, the disulfide compound, and ascorbic acid or a derivative formed during the oxidative process. This indicated that less copper was available for the formation of oxygen complexes which are not as stable as the disulfide complexes. Ellman's reagent (Nbs2) was reduced when it was substituted for the biological disulfides or when added, with EDTA, to solutions in which ascorbic acid, copper ion, and the biological disulfides had been allowed to interact. The complex formed with cystine was detected at 360 nm but the glutathione complex was not detected at this wavelength. It is proposed that disruption of cystine or glutathione complexes by EDTA results in formation of 2,3-diketogulonic acid which acts as a reductant of Ellman's reagent. 相似文献
9.
V I Grosheva 《Antibiotiki i khimioterapii͡a》2006,51(2):3-7
Analysis of circular dichroism spectra made it possible to offer a method for estimation of tetracycline solutions contamination with metal ions. By its sensitivity the method is much superior to the spectrophotometric one used at present for determination of the antibiotic purity. In the latter method formation of complexes with metals is traced by batochromic displacement of the absorption spectra. The new method is rapid, relatively selective and requires comparatively small quantities of the substance for the analysis, which provides its use under both laboratory and manufacture conditions. The method is based on identification of the circular dichroism spectra of tetracycline complexes with metals in the long wavelength region. The presence of the circular dichroism concervative bands with strictly defined extremums in the spectra of tetracycline low acid solutions contaminated by multiply charged metal ions allowed vs. the circular dichroism spectra of pure tetracycline sample to conclude that the solution contained admixtures and to suggest their nature. It was shown that the charge, ion radius and tetracycline:metal relation were the factors defining the mark and location of the dichroism band extremums. At lambda(extr)-410-415 nm the tetracycline complexes with light metal ions such as Mg2+, Al3+ and Ca2+ were detected by the circular dichroism negative band in the spectra, while the complexes with heavy metal ions such as Sc3+, Sr3+, Cu3+, Cd3+, Ba2+, Y3+ and the cerium subgroup lanthanides were detected by the circular dichroism positive band. The tetracycline complexes with the lanthanides of the second half of the yttrium subgroup (Ho(3+)-Lu3+) were characterized by the presence of the circular dichroism minimum at lambda(min)-425 nm. When the tetracycline concentration was above 1.5 x 10(-3) M, multiligand complexes with circular dichroism negative extremum at lambda(min)-400 nm formed. 相似文献
10.
Two potentiometric methods have been used to study the pH-dependent changes in proton binding that accompany complex formation between cytochrome c and cytochrome b5. With one method, the number of protons bound or released upon addition of one cytochrome to the other has been measured as a function of pH. The results from these studies are correlated with the complexation-induced difference titration curve calculated from the titration curves of the preformed complex and of the individual proteins. Both methods demonstrate that complex formation at acid pH is accompanied by proton release, that complex formation at basic pH is accompanied by proton uptake, and that the change in proton binding at neutral pH, where stability of complex formation is maximal, is relatively small. Under all conditions studied, the stoichiometry of cytochrome c-cytochrome b5 complex formation is 1:1 with no evidence of higher order complex formation. Although the dependence of complex formation on pH for interaction between different species of cytochrome c and cytochrome b5 are qualitatively similar, they are quantitatively different. In particular, complex formation between yeast iso-1-cytochrome c and lipase-solubilized bovine cytochrome b5 occurs with a stability constant that is 10-fold greater than observed for the other two pairs of proteins under all conditions studied. Interaction between these two proteins is also significantly less dependent on ionic strength than observed for complexes formed by horse heart cytochrome c with either form of cytochrome b5.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
11.
Crans DC Smee JJ Gaidamauskiene EG Anderson OP Miller SM Jin W Gaidamauskas E Crubellier E Grainda R Chi LH Willsky GR 《Journal of inorganic biochemistry》2004,98(11):1837-1850
The effects of Mo-hydroxylamido complexes on cell growth were determined in Saccharomyces cerevisiae to investigate the biological effects of four different Mo complexes as a function of pH. Studies with yeast, an eukaryotic cell, are particularly suited to examine growth at different pH values because this organism grows well from pH 3 to 6.5. Studies can therefore be performed both in the presence of intact complexes and when the complexes have hydrolyzed to ligand and free metal ion. One of the complexes we examined was structurally characterized by X-ray crystallography. Yeast growth was inhibited in media solutions containing added Mo-dialkylhydroxylamido complexes at pH 3-7. When combining the yeast growth studies with a systematic study of the Mo-hydroxylamido complexes' stability as a function of pH and an examination of their speciation in yeast media, the effects of intact complexes can be distinguished from that of ligand and metal. This is possible because different effects are observed with complex present than when ligand or metal alone is present. At pH 3, the growth inhibition is attributed to the forms of molybdate ion that exist in solution because most of the complexes have hydrolyzed to oxomolybdate and ligand. The monoalkylhydroxylamine ligand inhibited yeast growth at pH 5, 6 and 7, while the dialkylhydroxylamine ligands had little effect on yeast growth. Growth inhibition of the Mo-dialkylhydroxylamido complexes is observed when a complex exists in the media. A complex that is inert to ligand exchange is not effective even at pH 3 where other Mo-hydroxylamido complexes show growth inhibition as molybdate. These results show that the formation of some Mo complexes can protect yeast from the growth inhibition observed when either the ligand or Mo salt alone are present. 相似文献
12.
Complex formation between two new double-headed protease inhibitors from black-eyed peas, trypsin-chymotrypsin inhibitor (BEPCI) and a trypsin inhibitor (BEPTI), and trypsin and chymotrypsin was investigated in the concentration range from 10-8 to 10-4 M by titration experiments and gel filtration chromatography. Dissociation equilibrium constants measured for complexes detected in the titration experiments range from as large as 10-8 M for trypsin bound nonspecifically to the chymotrypsin site of BEPCI to as small as 10-18 M2 for the interaction of BEPCI with chymotrypsin. The identity and stoichiometry of complexes detected during titration experiments were confirmed by gel filtration of mixtures of native and fluorescently labeled proteases and inhibitors. Half-site reactivity is observed in the formation of complexes between BEPCI or BEPTI and trypsin and chymotrypsin at all experimentally practical concentrations. The double-headed complex contains 1 molecule each of trypsin, chymotrypsin, and BEPCI dimer. The bimolecular rate constants of complex formation between trypsin or chymotrypsin and isolated BEPCI oligomers range from 1.8 X 10(5) M-1 S-1 for chymotrypsin and BEPCI monomer to 4.4 X 10(7) M-1 S-1 for trypsin and the rapidly equilibrating BEPCI dimer. The estimated rate constants for the dissociation of half-site-liganded dimer complexes and liganded monomer complexes range from 7.5 X 10-3 S-1 for the trypsin-liganded BEPCI monomer complex to 1.6 X 10-6 S-1 for the chymotrypsin-liganded BEPCI dimer complex. 相似文献
13.
Investigation into the nature of substrate binding to the dipyrromethane cofactor of Escherichia coli porphobilinogen deaminase 总被引:3,自引:0,他引:3
The formation of the dipyrromethane cofactor of Escherichia coli porphobilinogen deaminase was shown to depend on the presence of 5-aminolevulinic acid. A hemA- mutant formed inactive deaminase when grown in the absence of 5-aminolevulinic acid since this strain was unable to biosynthesize the dipyrromethane cofactor. The mutant formed normal levels of deaminase, however, when grown in the presence of 5-aminolevulinic acid. Porphobilinogen, the substrate, interacts with the free alpha-position of the dipyrromethane cofactor to give stable enzyme-intermediate complexes. Experiments with regiospecifically labeled intermediate complexes have shown that, in the absence of further substrate molecules, the complexes are interconvertible by the exchange of the terminal pyrrole ring of each complex. The formation of enzyme-intermediate complexes is accompanied by the exposure of a cysteine residue, suggesting that substantial conformational changes occur on binding substrate. Specific labeling of the dipyrromethane cofactor by growth of the E. coli in the presence of 5-amino[5-14C]levulinic acid has confirmed that the cofactor is not subject to catalytic turnover. Experiments with the alpha-substituted substrate analogue alpha-bromoporphobilinogen have provided further evidence that the cofactor is responsible for the covalent binding of the substrate at the catalytic site. On the basis of these cumulative findings, it has been possible to construct a mechanistic scheme for the deaminase reaction involving a single catalytic site which is able to catalyze the addition or removal of either NH3 or H2O. The role of the cofactor both as a primer and as a means for regulating the number of substrates bound in each catalytic cycle is discussed. 相似文献
14.
Min Wu Wenyan Lu Ruth E. Santos Mark G. Frattini Thomas J. Kelly 《The Journal of biological chemistry》2014,289(44):30810-30821
The initial step in initiation of eukaryotic DNA replication involves the assembly of pre-replicative complexes (pre-RCs) at origins of replication during the G1 phase of the cell cycle. In metazoans initiation is inhibited by the regulatory factor Geminin. We have purified the human pre-RC proteins, studied their interactions in vitro with each other and with origin DNA, and analyzed the effects of HsGeminin on formation of DNA-protein complexes. The formation of an initial complex containing the human origin recognition complex (HsORC), HsCdt1, HsCdc6, and origin DNA is cooperative, involving all possible binary interactions among the components. Maximal association of HsMCM2–7, a component of the replicative helicase, requires HsORC, HsCdc6, HsCdt1, and ATP, and is driven by interactions of HsCdt1 and HsCdc6 with multiple HsMCM2–7 subunits. Formation of stable complexes, resistant to high salt, requires ATP hydrolysis. In the absence of HsMCM proteins, HsGeminin inhibits the association of HsCdt1 with DNA or with HsORC-HsCdc6-DNA complexes. However, HsGeminin does not inhibit recruitment of HsMCM2–7 to DNA to form complexes containing all of the pre-RC proteins. In fact, HsGeminin itself is a component of such complexes, and interacts directly with the HsMcm3 and HsMcm5 subunits of HsMCM2–7, as well as with HsCdt1. Although HsGeminin does not prevent the initial formation of DNA-protein complexes containing the pre-RC proteins, it strongly inhibits the formation of stable pre-RCs that are resistant to high salt. We suggest that bound HsGeminin prevents transition of the pre-RC to a state that is competent for initiation of DNA replication. 相似文献
15.
Guerra W de Andrade Azevedo E de Souza Monteiro AR Bucciarelli-Rodriguez M Chartone-Souza E Nascimento AM Fontes AP Le Moyec L Pereira-Maia EC 《Journal of inorganic biochemistry》2005,99(12):2348-2354
Pd(II) complexes with three antibiotics of the tetracycline family (tetracycline, doxycycline and chlortetracycline) were synthesized and characterized by elemental, thermogravimetric, and conductivity analyses, and infrared spectroscopy. The interactions between Pd(II) ions and tetracycline were investigated in aqueous solution by (1)H NMR. All the tetracyclines studied form 1:1 complexes with Pd(II) via the oxygen of the hydroxyl group at ring A and that of the amide group. The effect of the three complexes on the growth of bacterial strains sensitive and resistant to tetracycline was studied. The Pd(II) complex of tetracycline is practically as efficient as tetracycline in inhibiting the growth of two Escherichia coli (E. coli) sensitive bacterial strains and 16 times more potent against E. coli HB101/pBR322, a bacterial strain resistant to tetracycline. Pd(II) coordination to doxycycline also increased its activity in the resistant strain by a factor of 2. 相似文献
16.
Conformational changes accompanying the formation of binary and tightly bound ternary complexes of thymidylate synthetase and all possible combinations of three folate analogs (N-10-ethyl-quinazoline, folic acid triglutamate, and folic acid) and three deoxyribonucleotides (5-fluoro-2'-deoxyuridylic acid (FdUMP), 2'-deoxyuridylic acid (dUMP), and thymidylic acid (dTMP] were studied by means of ultraviolet difference spectroscopy. The amplitudes of the spectral changes upon ternary complex formation were 2-3-fold greater than those generated by formation of binary enzyme-nucleotide and enzyme-folate analog complexes. Difference spectra of the ternary complexes all showed a major increase in absorbance in the region of 320-340 nm, presumably due to perturbations of the folate analog chromophores, whereas decreases in absorbance occurred over a range of 260-310 nm. N-10-ethyl-quinazoline tended to form the complex with the greatest filtration efficiency on nitrocellulose filters, followed by folic acid triglutamate and folic acid, whereas among the nucleotides, the most stable complexes were formed with FdUMP, followed by dUMP and dTMP. A correlation was observed between the apparent stability of the ternary complex and the magnitude of the absorbance change in its difference spectrum. The formation of the various ternary complexes showed three different categories of rate behavior: 1) very rapid formation of the complex; 2) biphasic formation with a rapid phase and a slow phase requiring up to 90 min for completion; and 3) in the case of the ternary complex formed with enzyme, FdUMP, and folic acid, only a slow phase of binding. The slow formation of the latter complex was accompanied by concomitantly slow changes in the difference spectrum. However, in those cases of biphasic formation of the complexes, almost all of the spectral change occurred rapidly, and very little of it corresponded to the slow phase of complex formation. To accommodate these observations, a model is proposed involving a sequential interaction of the two subunits of thymidylate synthetase. 相似文献
17.
Michael G. Apps Ben W. Johnson Oliver B. Sutcliffe Sarah D. Brown Nial J. Wheate 《Journal of visualized experiments : JoVE》2014,(87)
Amide coupling reactions can be used to synthesize bispyridine-based ligands for use as bridging linkers in multinuclear platinum anticancer drugs. Isonicotinic acid, or its derivatives, are coupled to variable length diaminoalkane chains under an inert atmosphere in anhydrous DMF or DMSO with the use of a weak base, triethylamine, and a coupling agent, 1-propylphosphonic anhydride. The products precipitate from solution upon formation or can be precipitated by the addition of water. If desired, the ligands can be further purified by recrystallization from hot water. Dinuclear platinum complex synthesis using the bispyridine ligands is done in hot water using transplatin. The most informative of the chemical characterization techniques to determine the structure and gross purity of both the bispyridine ligands and the final platinum complexes is 1H NMR with particular analysis of the aromatic region of the spectra (7-9 ppm). The platinum complexes have potential application as anticancer agents and the synthesis method can be modified to produce trinuclear and other multinuclear complexes with different hydrogen bonding functionality in the bridging ligand. 相似文献
18.
The carboxyl-terminal domain (CTD) of eukaryotic initiation factor (eIF) 5 interacts with eIF1, eIF2beta, and eIF3c, thereby mediating formation of the multifactor complex (MFC), an important intermediate for the 43 S preinitiation complex assembly. Here we demonstrate in vitro formation of a nearly stoichiometric quaternary complex containing eIF1 and the minimal segments of eIF2beta, eIF3c, and eIF5. In vivo, overexpression of eIF2 and tRNA(Met)(i) suppresses the temperature-sensitive phenotype of tif5-7A altering eIF5-CTD by increasing interaction of the mutant eIF5 with eIF2 by mass action and restoring its defective interaction with eIF3. By contrast, overexpression of eIF1 exacerbated the tif5-7A phenotype because eIF1 forms unusual inhibitory complexes with a hyperstoichiometric amount of eIF1. Formation of such complexes leads to increased GCN4 translation, independent of eIF2 phosphorylation (general control derepressed or Gcd(-) phenotype). We also provide biochemical evidence indicating that the association of eIF5-CTD with eIF2beta strongly enhances its binding to eIF3c. Our results suggest strongly that MFC formation is an ordered event involving specific enhancement of eIF5-CTD binding to eIF3 on its binding to eIF2beta. We propose that the primary function of eIF5-CTD is to serve as an assembly guide by rapidly promoting stoichiometric MFC assembly with the aid of eIF2 while excluding formation of nonfunctional complexes. 相似文献
19.
Various N-alkylhydroxylamines such as N-hydroxyamphetamine react with prostaglandin synthase (PGHS) from sheep seminal vesicles, with the formation of new complexes characterized by a Soret peak around 421 nm. These complexes are very stable toward O2 or dithionite but are destroyed upon oxidation by Fe(CN)6K3 with regeneration of starting PGHS-FeIII. Their spectral characteristics, chemical properties, and routes of formation (either by direct oxidation of RNHOH or by in situ reduction of RNO2 in the presence of dithionite) are very similar to those previously reported for nitrosoalkane complexes of hemoglobin-, myoglobin-, and cytochrome P-450-FeII. Their FeII-N(O)R structure was completely confirmed in the case of N-hydroxyamphetamine, both by extraction of the heme complex by butanone and by identification to authentic protoporphyrin IX-FeII-N(O)-amphetamine, and by insertion of this authentic complex into apoPGHS. Phenylhydroxylamine also reacts with PGHS-FeIII to give a PGHS-FeII-N(O)Ph complex which is not stable in the presence of dithionite because of its weaker PGHS-FeII-N(O)R bond when compared to PGHS-FeII-nitrosoalkane complexes. The ability of various N-alkylhydroxylamines to form PGHS-FeII-N(O)R complexes greatly depends upon their hydrophobicity. Actually, CH3NHOH and C2H5NHOH are totally inactive whereas about 10 molar excess of N-hydroxyamphetamine and C6H5NHOH already lead to 50% complex formation. This is in favor of an hydrophobic environment of the heme in PGHS. Finally, PGHS engaged in such FeII-nitrosoalkane complexes completely loses its dioxygenase activity, suggesting that N-substituted hydroxylamines or compounds that can be metabolized in vivo to give such hydroxylamines could act as strong PGHS inhibitors. 相似文献
20.
Martin SR 《Biophysical chemistry》1979,10(3-4):319-326
The interaction of Ca2+ and Mg2+ with three Tetracycline antibiotics (tetracycline, chlorotetracycline, and oxytetracycline) has been investigated. Spectrophotometric measurements have been used to determine the apparent association constant for this interaction as a function of pH. It is shown that the results are consistent with a model in which the metal ion can form complexes with both the fully-deprotonated and mono-protonated forms of the Tetracycline. The temperature-jump relaxation method has been used to measure the kinetics of formation of the complexes of Mg2+ with the Tetracyclines. The results are compared with those of previous studies of Mg2+ complex formation reactions and it is shown that the data is consistent with the normal dissociative model. A possible role for metal ion chelation in the mechanism of antibacterial action of the Tetracyclines is discussed. 相似文献