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GOTTARDI
Redox-iodometry: a new potentiometric method.
Gottardi W, Pfleiderer J.
Anal Bioanal Chem. 2005 Jul;382(5):1328-38. Epub 2005 Jun 25. Erratum in: Anal Bioanal Chem. 2005 Oct;383(4):721-2.
"A new iodometric method for quantifying aqueous solutions of iodide-oxidizing and iodine-reducing substances, as well as plain iodine/iodide solutions, is presented. It is based on the redox potential of said solutions after reaction with iodide (or iodine) of known initial concentration. Calibration of the system and calculations of unknown concentrations was performed on the basis of developed algorithms and simple GWBASIC-programs. The method is distinguished by a short analysis time (2-3 min) and a simple instrumentation consisting of pH/mV meter, platinum and reference electrodes. In general the feasible concentration range encompasses 0.1 to 10(-6) mol/L, although it goes down to 10(-8) mol/L (0.001 mg Cl2/L) for oxidants like active chlorine compounds. The calculated imprecision and inaccuracy of the method were found to be 0.4-0.9% and 0.3-0.8%, respectively, resulting in a total error of 0.5-1.2%. Based on the experiments, average imprecisions of 1.0-1.5% at c(Ox)>10(-5) M, 1.5-3% at 10(-5) to 10(-7) M, and 4-7% at <10(-7) M were found. Redox-iodometry is a simple, precise, and time-saving substitute for the more laborious and expensive iodometric titration method, which, like other well-established colorimetric procedures, is clearly outbalanced at low concentrations; this underlines the practical importance of redox-iodometry."
Properties of an enzyme-based low-level iodine disinfectant.
Duan Y, Dinehart K, Hickey J, Panicucci R,
Kessler J, Gottardi W.
J Hosp Infect. 1999 Nov;43(3):219-29.
“An enzyme-based iodine (EBI) disinfectant that continuously generates free molecular iodine in a controlled fashion was developed and evaluated for use in disinfecting flexible fibreoptic endoscopes (FFEs). EBI is a powder concentrate that produces iodine from sodium iodide and calcium peroxide when catalyzed by horseradish peroxidase. After dissolution in water, it delivers relatively high concentrations of free molecular iodine (> 15 ppm) at relatively low concentrations of total iodine (30-40 ppm). It demonstrates the ability to function as an effective low level iodine disinfectant by rapidly inactivating bacteria, fungi and viruses. A unique feature of the EBI system is the ability to reoxidize reduced iodine which results in a constant level of active (free molecular) iodine during use. EBI inactivates Mycobacterium bovis var BCG more rapidly than 2% glutaraldehyde (Cidex-7). Its sporicidal activity, however, was found to be slower than the aldehyde formulation. The qualification of EBI for use as a practical disinfectant was shown by its negligible toxicity in dermal, ocular, oral and inhalation studies on animals, which is attributed to the low level of total iodine in the solution.”
Iodine and disinfection: theoretical study on mode of action, efficiency, stability, and analytical aspects in the aqueous system.
Gottardi W.
Arch Pharm (Weinheim). 1999 May;332(5):151-7.
"Although they have been in use for nearly 170 years, the mode of action of iodine-based disinfectants is not yet clearly understood, as is manifested, for example, in diverging judgements about the relevance of the individual iodine species. Although studies based on calculated equilibrium concentrations in pure iodine solutions have already been done, there is a lack of knowledge about iodine solutions in the presence of additional iodide which would be of intrinsic importance for disinfection practice. Therefore, a re-calculation was undertaken considering variations of this parameter in the pH range 0-14. The presented calculations concern fresh iodine solutions not affected by disproportionation (iodate formation) and provide information about the equilibrium concentrations of the species I, I2, I3, I5-, I6(2-), HOI, O1-, HI2O-, IO2- and H2OI+. Additional iodide and the pH value have a very pronounced influence on the individual equilibrium concentrations (several powers of ten); hence, conditions can be indicated where the number of species of virtual importance is drastically reduced. In the most common case with iodine in the presence of additional iodide at pH < 6, only I-, I2 and I3- play a role. In the absence of additional iodide, at pH 8-9 and at high dilution (c(I2) < 10(-5) M), on the other hand, HOI accounts for over 90% of the oxidation capacity. At high iodide concentration (e.g., Lugol's solution) the species I5- and I6(2-) make up 8.2% of the oxidation capacity. The iodine cation H2OI+, frequently quoted as an active agent in disinfection, is without any relevance under the conditions occurring in practice, as are IO- and HI2O- which become important only at pH > 10. The stability problem (i.e. rate of iodate formation) arising at pH > 6 can be reduced to hypoiodous acid, as manifested in the simple rate law d[IO3]/dt = 0.25 [HOI]3/[H+] which allows an estimation of stability under weakly alkaline conditions. The results of this study allow us to deduce general qualities of aqueous iodine solutions, such as reactivity, stability, and analytical aspects, and to estimate major disinfection-orientated properties such as microbicidal activity, irritation, and incorporation effects. Though the calculations consider primarily preparations devoid of polymeric organic compounds capable of complexing iodine species, the results can be largely transferred to iodophoric preparations."
Control of the amount of free molecular iodine in iodine germicides.
Hickey J, Panicucci R, Duan Y, Dinehart K, Murphy J, Kessler J, Gottardi W.
J Pharm Pharmacol. 1997 Dec;49(12):1195-9.
“Horseradish peroxidase has been used to generate iodine compositions that comprised principally free molecular iodine. The concentration of free molecular iodine in these enzyme-based compositions ranged from 44 to 63% of the thiosulphate titratable iodine; this is substantially higher than the corresponding value for the povidone-iodine preparation betadine. The biocidal efficacy of these compositions was proportional to the concentration of free molecular iodine. Iodine compositions with relatively low total iodine concentrations but high levels of free molecular iodine (20-175 ppm) killed Staphylococcus aureus and spores of Bacillus subtilis more rapidly than betadine. The effects of normal saline and these enzyme-based iodine compositions on the rate of epidermal regeneration in superficial swine wounds were comparable. These results suggest that an effective germicide containing a high level of molecular iodine need not be irritating or toxic.”
Iodine and Iodine Compounds
Gottardi W
Chapter 8 in Block, SS. Disinfection, Sterilization, and Preservation, 4th edition. Lea & Febiger, 1991, pp 152-165.
"Iodine is an excellent prompt effective microbicide with a broad range of action that includes almost all of the important health-related microorganisms, such as enteric bacteria, enteric viruses, bacterial viruses, and protozoan cysts.... Mycobacteria and the spores of bacilli and clostridia can also be killed by iodine... Furthermore, iodine also exhibits a fungicidal and trichomonacidal activity.... As is expected, varying amounts of iodine are necessary to achieve complete disinfection of the different classes of organisms. Within the same class, however, the published data on the disinfecting effect of iodine correspond only to a small extent. In particular, the published killing times of spores... and viruses... are widely disparate. One reason for this might be the non-uniform sensitivity of microorganisms to iodine, which applies not only to the type of organism but also to the growth conditions.... Bacterial isolates... from water systems disinfected by iodine showed differences (which had, however, not always the same sign) of up to 4 logs decrease after contact with iodine... if grown in brain heart infusion or after cultivation in phosphate buffer....
"Comparison of previously published references concerning effectiveness in disinfection processes of different microorganisms are difficult because of the myriad of different environmental conditions existing when experiments are conducted, e.g., pH value, temperature, concentration and type of iodine preparation, time of exposure to the disinfectant, and amount and type of dissolved organic and inorganic substances. Another problem is the fact that, in general, most of these conditions are not described in detail, and an exact comparison of the germicidal effectiveness of iodine against different organisms, as well as a comparison with other halogens, is therefore virtually impossible. In spite of these difficulties, some authors have tried to summarize the disinfecting properties of iodine and the other halogens by reviewing the literature and analyzing the existing data. The most important conclusions are...."
The decrease of efficiency of povidone-iodine preparations by blood: Model experiments on the reaction of iodine containing disinfectants with protein constituents
Gottardi W, Koller W
Proceedings, Third Conference on progress in chemical disinfection, 1986.
"The reaction of blood with povidone-iodine containing preparations results in a decrease of titrable iodine (C-ox) and a significant raise of the iodide concentration. As a consequence, the concentration of free iodine (I2) decreases more than C-ox, because the equilibrium of the triiodide formation, I2 + I- <=> I3-, is shifted to the right. The extent of the decrease of C-ox and I2 is not proportional to the amount of blood but decreases with the latter. Thus, the reaction of a 10% povidone-iodine solution with 20% blood gave rise to a decrease of 27-40% C-ox and 35-55% I2, while in the case of 100% blood the decrease was 80-88 resp. >90%.
"Since I2 is an important parameter, which largely correlates with the rate of killing microorganisms, the action of blood (mainly at concentrations > 20%) on povidone-preparations can cause a significant loss of disinfecting power.
"The reaction with blood takes place immediately and its extent -- as well as the fast reaction rate -- depends, as can be shown by experiments with defined protein constituents, mainly on the content of protein bound sulfur, in particular of the amino acids cysteine and methionine. Histidine, thyrosine, cytosine, albumine and uracil react also reducing iodine, but much slower than do cysteine and methionine. Alanine, glycine, arginine, asparagine, lysine, guanine, adenine and cystine however did not react with iodine under the selected conditions (aqueous solution, pH 7, 25oC)."
[Germicidal experiments with aqueous PVP-iodine-containing disinfecting solutions: effect of the content of free iodine on the bactericidal action against Staphylococcus aureus]
Gottardi W, Puritscher M.
Zentralbl Bakteriol Mikrobiol Hyg [B]. 1986 Jul;182(4):372-80. German.
[abstract only]
"The bactericidal activity against Staph. aureus of three PVP-iodine preparations in different concentrations, and of 0.1 mol/L KI-solutions with concentrations of free iodine corresponding to the povidone-iodine preparations, was evaluated at reaction times of 7, 15, 30 and 60 seconds. The concentration of free iodine has been measured potentiometrically during the entire reaction time. In all cases it has been confirmed that the bactericidal activity is increasing with the concentration of free iodine. However, there have been found differing correlations between the logarithmic decrease of germs (RF-value), the concentration of free iodine and the reaction time (statistical evaluation of the results by means of linear multiple regression: RF = a0 + a1 log [I2] + a2 log t). Referring to the concentration of free iodine the bactericidal activity in the range of RF approximately equal to 4-6 is increasing as follows: Povidone-iodine washing concentrate much greater than iodine in KI (0.1 mol/l) greater than Povidone-iodine mucosal disinfectant greater than aqueous solution of povidone iodine. This sequence is explained by differences of composition. So it is assumed that the surface active ingredients facilitate the penetration of molecular iodine. The observed correlations show that there is probably no exact mathematical relation of general validity for iodine preparations of different composition between the concentration of free iodine and the RF-value. However, for one and the same preparation such a correlation can be derived and enables to make predictions about the bactericidal activity, which can be expected as a consequence of the concentration of free iodine."
The influence of the chemical behaviour of iodine on the germicidal action of disinfectant solutions containing iodine.
Gottardi W.
J Hosp Infect. 1985 Mar;6 Suppl A:1-11.
[citation only]
Potentiometric evaluation of the equilibrium concentrations of free and complex bound iodine in aqueous solutions of polyvinylpyrrolidone-iodine (Povidone-iodine) [article in German]
Gottardi W
Fresenius Z Anal Chem (1983) 314: 582-585.
"The equilibrium concentrations of I2 and I3- in aqueous povidone-iodine solutions (0.001 - 20.0 %, pH4, 25oC) have been evaluated from the redox potential and the iodide concentration as measured by the iodide electrode (HOI, OI-, H2O+I and IO-3 can be neglected under the chosen conditions). The values obtained for I-, I2, I3- and C-ox (= iodometrically titrable iodine) indicate that the amount of iodine which is complex bound to the povidone matrix consists of HI3 -- and I2 -- groups. At concentrations > 1%, it represents nearly the whole oxidation capacity, while it can be neglected below 0.01%. The concentration of the free, molecular iodine (I2) only comes to 4.5 x 10-6 m/l (1.1ppm) in the 20% solution and increases to a maximum of ~ 10-4 m/l (25.4 ppm) in the 0.1% solution. The precision of the method is discussed and the overall error of the calculated values was found to be in the range of 8 - 12%."
[The formation of iodate as a reason for the decrease of efficiency of iodine containing disinfectants (author's transl)]
Gottardi W.
Zentralbl Bakteriol Mikrobiol Hyg [B]. 1981;172(6):498-507. German.
"Methods are given to calculate the iodate equilibrium concentrations in aqueous solutions of iodine, containing additional iodide as well as the reaction times concerning the transformation of iodine to iodate. Using the results, which have been obtained evaluating in this manner solutions of triiodide (CI2 = CI- = 10(-6)--10(-1) M/l) as well as 0.03 M iodine solutions containing varying amounts of iodide (0--0.12 M/l) the following conclusions concerning the stability of iodine containing disinfecting agents can be made; 1. Below pH 6 a decrease of the disinfecting effectiveness owing to the formation of iodate can be excluded. 2. Above pH 7 the formation of iodate, whose extent depends extremely on the pH-value as well as the iodide concentration, has to be regarded very carefully. Raising the pH-value lowers the stability (iodate formation increases) while raising the iodide concentration improves the stability (iodate formation is reduced). 3. Because of the stabilizing effect of the iodide ion, provided that its concentration is high enough, the opposite effect of the pH-value can be overcompensated and as a result of this iodine containing agents can exhibit a stability sufficient for practice also in the weak alkaline range (pH less than 9)."
[Redoxpotential and germicidal action of aqueous halogen solution (author transl)]
Gottardi W.
Zentralbl Bakteriol [B]. 1980;170(5-6):422-30. German.
[abstract only]
"Methods are given to calculate the equilibrium concentrations of both halogene solutions (chlorine, bromine and iodine) in the presence of additional halide and of chlorine solutions in the presence of chloride and ammonia. With the aid of these values and the redoxpotentials which have been determined from them is demonstrated that there is a very complicated connection between the latters and the total as well as the equilibrium concentrations. It depends on the kind of the halogene, the pH-value and the presence of substances which can react with the halogene (halides, NH-compounds) and can not be described by the simple formula: increase of the redoxpotential approximately increase of the equilibrium concentrations of germicidal hydrolysis products and as a consequence of the death rates. On the contrary a reduction of the total halogene concentration may cause an increase of the redoxpotential as well as the addition of halide may lower the redoxpotential while the concentration of strong germicidal "free halogene" remains unchanged. The redoxpotential therefore is not a mean to make reliable predictions concerning the germicidal action of halogene solutions."
[Aqueous iodine solutions as disinfectants: composition, stability, comparison with chlorine and bromine solution (author's transl)]
Gottardi W.
Zentralbl Bakteriol [B]. 1978 Sep;167(3):206-15. German.
[abstract only]
"The equilibrium concentrations of aqueous iodine solutions in dependence of the total concentration and the pH-value have been calculated with and without regard of the iodate formation. The values obtained by the latter methode enabled by application of the known rate law to calculate the initial rate of the iodate formation and to draw from this conclusions concerning the stability of iodine solutions. On the grounds of these calculations to aqueous iodine solutions in the concentration and pH-range which is relevant for disinfection (greater than 10(-5) M/l, pH 6--9) one can attribute a stability sufficient for the use in practice and - unlike chlorine and bromine solutions - a content of bactericidal "free halogene" which is higher and independent of the pH-value. The disinfecting action of the iodine cation (H2O+J) which is supposed to be very powerful can be neglected because of its low concentration (10(-3)--10(-6%) of the total concentration). Hypoiodic acid which has already been converted into iodate by disproportionation is as good as lost for the disinfection because of the extremely slow reverse reaction."
[On the usability of N-iodo compounds as disinfectants (author's transl)]
Gottardi W.
Zentralbl Bakteriol [B]. 1978 Sep;167(3):216-23. German.
[abstract only]
"The usability of N-iodo compounds for disinfecting purposes has been investigated with the help of the equilibrium concentrations in aqueous solution, which have been calculated both with and without regard of the iodate formation, and the rate of iodate formation, which has been deduced from the latter. The following conclusions can be drawn: Fresh and diluted aqueous solutions of N-iodo compounds exhibit HOJ-concentrations corresponding with the sum HOJ + J2 ( = "free halogene") in pure iodine solutions, which let expect a similar bactericidal behaviour of this class of compounds. Compared with iodine solutions, however, a higher rate of iodate formation and therefore a less stability of these solutions can be established, which is caused by the throughout higher HOJ-concentration. Observing certain conditions (pH less than 7; C less than 10(-5) M/l) and unless a not to long interacting time is required the stability should be sufficient for disinfecting purposes. Of particular interest is the possibility to investigate, virtually in absence of molecular iodine, the bactericidal action of the HOJ. A common use in practice will depend on the costs, which, as far as the purchasable N-iodo-succinimide is concerned, are very high, hence it should not come at present into consideration as an alternative of the much more inexpensive elemental iodine."
[Aqueous chloride and bromine solutions as disinfectants: composition, redox potential, differences of reactivity (author's transl)]
Gottardi W.
Zentralbl Bakteriol [Orig B]. 1977 Oct;165(2):235-41. German.
[abstract only]
"A method is given to calculate the equilibrium concentrations of the molecules and ions emerging from the hydrolysis and dissociation of chlorine and bromine in aqueous soltuion. The differing influence the pH value and the initial (total) halogene concentration exerts to the HOX- and X2-equilibrium concentration is discussed. From the calculated equilibrium concentrations and tabulated standard reduction potentials the redox potentials of chlorine and bromine solutions at various pH values are calculated. No correlation between the reactivity and the redox potential of the two halogens was observed. Two possible explanations for the differing reactivity of chlorine and bromine against proteins are presented."