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PubMed1982

[The broncholytic effect of buffers applied by inhalation. A new pharmacological concept (author's transl)].

A new method was developed by which the tone of bronchial smooth muscle can be measured breath by breath in man. Thereby state and reactions of bronchial smooth muscle can be studied. Former investigations had shown that carbonic anhydrase inhibitors have a broncholytic effect. The mechanism of action presumably is the prevention by carbonic anhydrase inhibitors of CO2 induced changes of pH within the bronchial epithelium occurring breath by breath with different partial pressures of CO2. Principally a stabilisation of pH can also be achieved by buffers. Therefore the broncholytic effect of buffers was tested and a 10% buffer solution of phosphat and Tris (THAM) buffer applied by inhalation in two healthy volunteers. In both cases a significant bronchodilation was seen, which in case of phosphate was substantially greater than in case of conventional broncholytics (e.g., fenoterol). As concerns onset and duration of the broncholytic effect, buffers are similar to conventional broncholytics. It is great advantage that buffers do not stimulate bronchial peristalsis and do not have cardiac side effects, contrary to conventional broncholytics.

Adult↗
PubMed1980

Effect of p-chloromercurybenzoate on the MDH-activity of cytosol and rat liver submitochondrial fractions in different buffers.

The effect of p-chloromercurybenzoate (p-CMB) on the MDH-activity of cytosol and submitochondrial fractions (matrix and inner membranes) of rat liver is studied in different buffer systems with identical pH. It is found that p-CMB has two effects on the MDH-activity, depending on the subcellular localization of the enzyme and on the type of buffer used: inhibitory (for the enzyme of the three fractions in HEPES-NaOH and potassium-phosphate buffers) and activating (for the enzyme of the submitochondrial fractions in Tris-HCI buffer). The effect of the SH-reagent on the formation and stability of enzyme-substrate complexes in the different buffers is also studied, as well as the temperature dependence of the p-CMB action on the MDH-activity of the preparations. It is found that the association of m-MDH with the inner mitochondrial membranes does not change its kinetic behaviour. The probable different conformation of the mitochondrial enzyme in the different buffer systems is discussed.

Animals↗
PubMed1995

Buffered lidocaine: analgesia for intravenous line placement in children.

OBJECTIVES: To evaluate the effectiveness of intradermal buffered lidocaine as analgesia before intravenous line (i.v.) placement in children. METHODS: This was a randomized clinical trial undertaken in the emergency department (ED) of a regional children's hospital. Participants were children 8 to 15 years old, seen in the ED and in need of i.v. lines. They were enrolled by three ED nurses. Participants were randomized to receive either intradermal buffered lidocaine or no analgesia. Before placement of the i.v. line, patients recorded the amount of pain they were in (baseline pain) on a visual analog pain scale. The primary outcome measure was amount of pain caused by the initial i.v. attempt, even if that attempt was unsuccessful. This was recorded by the participant on a visual analog scale. Demographic characteristics, the number of attempts to successful placement, and the time required to place the i.v. line were also recorded. Differences in pain of initial i.v. attempt and time to place the i.v. line were evaluated with the Mann-Whitney U test. Differences in success of i.v. line placement were evaluated with the chi 2 test. RESULTS: Fifty-nine patients completed the study. Thirty received buffered lidocaine, and 29 received no analgesia before i.v. line placement. There was no significant difference between the two groups with regard to baseline pain or demographic characteristics. The median level of pain of the initial i.v. attempt as measured by the visual analog scale was 2.3 in the buffered-lidocaine group and 4.4 in the no-lidocaine group. Thirty-three percent of patients in the lidocaine group and 28% percent in the no-lidocaine group required more than one i.v. attempt. The median time to i.v. line placement was 10 minutes in the lidocaine group and 6 minutes in the no-lidocaine group. CONCLUSIONS: Use of intradermal buffered lidocaine is an effective way to diminish the pain of i.v. line placement in children 8 to 15 years of age. There was no difference in i.v. success rate in this study; however, larger numbers of patients would be required to detect statistically significant differences. We recommend the routine use of intradermal buffered lidocaine for analgesia before i.v. line placement in older children in all but emergent situations.

Adolescent↗
PubMed1975

[Year-round buffering of cattle feed mixture and its effect on metabolism and productivity].

Commercial feed mixture was buffered with a 2% and 3% admixture of bentonite buffer in two beef cattle herds in the course of one year. The mixtures were fed on a continuous basis. The two-per-cent buffer concentration was tested in 110 test animals with 104 control animals and the three-per-cent concentration in 50 test animals with 50 controls. Throughout the trial the over-all health condition remained unchanged, the hematocrit and hemoglobin values were balanced in both groups. The biochemical indices were better in the test groups: hypocalcemia improved (in the controls it grew worse), magnesiemia was slightly increased, the inorganic serum factor did not go beyond physiological limits, and acidosis did not occur (as distinct from the control animals). The levels of transaminases (GOT, GPT), glutamic acid dehydrogenase, total serum protein, alkaline phosphatase as well as ammonia and urea in blood serum were at physiological values with po-differences within groups. In the case of the three-per-cent buffer concentration the daily gains were higher by 0.073 kg, and in the two-per-cent concentration by 0.058 kg, in the test animals. The average annual gain was higher by 25.5 kg, and by 18.3 kg, respectively. With respect to the price of buffer and to the efficiency of the animals tested, the economic indices of feed mixture buffering are highly effective.

Alanine Transaminase↗
PubMed1996

Effect of different buffers on the biocompatibility of CAPD solutions.

Commercially available solutions for continuous ambulatory peritoneal dialysis (CAPD) affect the viability and function of the cells in the peritoneal cavity. The low biocompatibility of the solutions may be caused by a low pH, hyperosmolality, high glucose content, and lack of potassium, glutamine, and other components essential for normal cellular functions. The nature of the buffer employed is also important for the cytotoxicity of the solutions. Lactate, the most frequently used buffer, has been shown to inhibit cellular functions important for the peritoneal defense system including phagocytosis, bacterial killing, and secretion of cytokines. It is generally believed that the cytotoxicity of lactate is caused by lowering of intracellular pH and impairment of metabolism due to changed redox potentials. However, the cytotoxicity of lactate is highly dependent upon the pH of the solutions, indicating that passive or active diffusion across the cell membrane is determining the effects of lactate. Bicarbonate has been heavily advocated as an alternative buffer because it is the most important naturally occurring buffer in plasma and it enables a pH of approximately 7.4 in the solutions. However, due to sedimentation of calcium carbonate (CaCO3) and production of toxic glucose metabolites it is difficult to prepare and store bicarbonate-based solutions. Moreover, investigations have revealed that even bicarbonate-based solutions are not optimal regarding biocompatibility, presumably due to a paradoxical intracellular acidification caused by influx of carbon dioxide (CO2). More recently, the effect of other buffers such as pyruvate and histidine have been examined. Especially pyruvate is a promising new buffer candidate.

Acid-Base Equilibrium↗
PubMed1995

Effects of the medium HCO3-/CO2 buffer system on differentiation and intermediary metabolism properties of rabbit proximal tubule cells in primary culture.

In vivo, bicarbonate can affect proximal tubule intermediary metabolism, including gluconeogenesis, ammoniagenesis and maintenance of the mitochondrial substrate supply. In vitro, rabbit proximal tubule cells (RPTC) in primary culture revert from gluconeogenesis to glycolysis and their mitochondrial metabolism remains lower than in vivo. To determine whether the bicarbonate buffer system could have an effect on these deregulations, RPTC in primary culture grown in the absence of insulin and glucose in the culture medium were developed either with the standard sodium bicarbonate buffer with 5% CO2 or with a Hepes hydrogen ion buffer in the presence of 0.5% CO2. Duration of the bicarbonate-free cultures was increased until at least day 17 after seeding, compared with day 11 in bicarbonate-buffered cultures. As could be expected, succinate dehydrogenase activity remained stable as a function of time in bicarbonate-free cultures while an early marked decrease of this activity occurred from seeding in cultures developed in the presence of bicarbonate buffer. Compared to bicarbonate-buffered cells, higher phosphoenolpyruvate carboxykinase activity concomitant with lower intracellular lactate dehydrogenase activity was observed in cultures developed in the absence of bicarbonate, which is indicative of closer carbohydrate metabolism orientation to the in vivo situation for RPTC. Immunofluorescence staining of RPTC with monoclonal antibodies directed to neutral endopeptidase (NEP), and dipeptidyl-peptidase IV (DPP II) showed similar extensive labelling with DPP and NEP in both culture conditions. Confocal microscopy analysis of NEP subcellular distribution, showed exclusive targetting of NEP to the apical plasma membranes. In both models, cAMP production was stimulated by parathyroid hormone and unaffected by arginine vasopressin. In conclusion, bicarbonate withdrawal from the culture medium (without changing the pH of the medium) allows a marked improvement of mitochondrial capacity and carbohydrate metabolism pattern without any loss of differentiated properties.

Adenosine Triphosphate↗
PubMed1998

Enthalpy and heat capacity changes for the proton dissociation of various buffer components in 0.1 M potassium chloride.

Enthalpy and heat capacity changes for the deprotonation of 18 buffers were calorimetrically determined in 0.1 M potassium chloride at temperatures ranging from 5 to 45 degrees C. The values of the dissociation constant were also determined by means of potentiometric titration. The enthalpy changes for the deprotonation of buffers, except for the phosphate and glycerol 2-phosphate buffers, were found to be characterized by a linear function of temperature. The enthalpy changes for the second dissociation of phosphate and glycerol 2-phosphate where divalent anion is formed on dissociation were fitted with the second order function of temperature rather than the first order. Temperature dependence of buffer pH calculated by using the enthalpy and heat capacity changes obtained was in good agreement with the temperature variation of the pH values actually measured in the temperature range between 0 and 50 degrees C for all the buffers studied. On the basis of the results obtained, a numeric table showing the temperature dependence of pK values for the 18 buffers is presented.

Buffers↗
PubMed1981

Effect of buffer constituents on rat liver 3-hydroxy-3-methyl glutaryl coenzyme A reductase.

Rat liver microsomes prepared in Tris buffer exhibited 3 to 10 times higher 3-hydroxy-3-methyl glutaryl CoA reductase specific activity than microsomes prepared with potassium phosphate buffer. This higher activity was observed in rats killed during mid-light cycle, but microsomes from rats killed during mid-dark cycle showed no significant difference in enzyme activity between buffers. When microsomes prepared in the 2 different buffers were preincubated with ATP and MG++, enzyme activity was inhibited to the same extent. The cytosol fraction in each of the 2 different buffer preparations possessed similar phosphatase activity. The higher 3-hydroxy-3-methyl reductase activity in Tris buffer, therefore, does not appear to be due to differences in phosphorylation or dephosphorylation activity.

Adenosine Triphosphate↗
PubMed2006

Zinc-buffering capacity of a eukaryotic cell at physiological pZn.

In spite of the paramount importance of zinc in biology, dynamic aspects of cellular zinc metabolism remain poorly defined at the molecular level. Investigations with human colon cancer (HT-29) cells establish a total cellular zinc concentration of 264 microM. Remarkably, about 10% of the potential high-affinity zinc-binding sites are not occupied by zinc, resulting in a surplus of 28 muM ligands (average Kd(c) = 83 pM) that ascertain cellular zinc-buffering capacity and maintain the "free" zinc concentration in proliferating cells at picomolar levels (784 pM, pZn = 9.1). This zinc-buffering capacity allows zinc to fluctuate only with relatively small amplitudes (DeltapZn = 0.3; below 1 nM) without significantly perturbing physiological pZn. Thus, the "free" zinc concentrations in resting and differentiated HT-29 cells are 614 pM and 1.25 nM, respectively. The calculation of these "free" zinc concentrations is based on measurements at different concentrations of the fluorogenic zinc-chelating agent and extrapolation to a zero concentration of the agent. It depends on the state of the cell, its buffering capacity, and the zinc dissociation constant of the chelating agent. Zinc induction of thionein (apometallothionein) ensures a surplus of unbound ligands, increases zinc-buffering capacity and the availability of zinc (DeltapZn = 0.8), but preserves the zinc-buffering capacity of the unoccupied high-affinity zinc-binding sites, perhaps for crucial physiological functions. Jointly, metallothionein and thionein function as the major zinc buffer under conditions of increased cellular zinc.

Cell Differentiation↗
PubMed1993

Is buffering capacity the principle role of the jelly coat in Bufo arenarum fertilization?

1. Dejellied Bufo arenarum oocytes can be fertilized in Ringer-Phosphate buffer with the same efficiency as jellied (control) oocytes. 2. Ringer-Phosphate buffer at pH = 7.4 not only provides buffering capacity but also the delta pH necessary for the acrosomal reaction. 3. The use of Ringer-TRIS buffer at pH = 7.4 does not render as good as Ringer-Phosphate buffer results, in terms of fertilization percentages. 4. Insemination of oocytes in Ringer-TRIS buffer interferes with early development.

Animals↗
PubMedDate not supplied

Life stressors, drinking patterns, and depressive symptomatology: ethnicity and stress-buffer effects of alcohol.

This paper seeks to extend previous research on stress buffer effects of alcohol use using data from a tri-ethnic community sample of 1,784 respondents. Differences in buffer effects between Anglos, Blacks, and Mexican Americans are examined to explore possible racial/ethnic variation in the role or function of alcohol vis-à-vis life stress and depressive symptoms. Both acute life events and chronic financial stress are examined to clarify the conditions under which buffer effects are most and least salient in these groups. The findings indicate that alcohol buffer effects are most pronounced among males with regard to life event stress and depression. Ethnic differences in buffer effects were suggested among males for life events, though statistical controls for demographic factors, fatalism, and religiosity accounted for these differences. The implications of these findings are examined, and the paper generally highlights the need to view alcohol use and alcohol buffer effects in the context of more general coping orientations.

Adaptation, Psychological↗
PubMed1992

A prospective controlled evaluation of TEST-yolk buffer in the preparation of sperm for human in vitro fertilization in suspected cases of male infertility.

OBJECTIVE: To evaluate sperm preincubation in tes and tris (TEST)-yolk buffer as a potential enhancing agent of fertilizing capacity of sperm during human in vitro fertilization (IVF). DESIGN: Oocytes obtained during IVF were divided into two groups: one group fertilized with TEST-yolk buffer-treated sperm and the other group with standard-prepared sperm. SETTING: The University of Southern California IVF Program. PATIENTS: Thirty-nine couples with suspected male factor infertility undergoing IVF. INTERVENTIONS: Preinsemination incubation of sperm in TEST-yolk buffer for 24 hours. MAIN OUTCOME MEASURES: Fertilization rates in vitro. RESULTS: TEST-yolk buffer-treated sperm fertilized 140 of 241 oocytes (58%), whereas control sperm fertilized 108 of 251 oocytes (43%). Of four couples who had previously failed to fertilize during IVF, one fertilized with both specimens and three fertilized with TEST-yolk buffer-treated sperm only. CONCLUSIONS: TEST-yolk buffer pretreatment of sperm for 24 hours results in higher fertilization rates during IVF among suspected male factor patients.

Egg Yolk↗
PubMed1989

Capillary electrophoresis of proteins in buffers containing high concentrations of zwitterionic salts.

A method for improving protein separations in capillary zone electrophoresis utilizing high concentrations of zwitterionic buffer additives was examined. Lysozyme and alpha-chymotrypsinogen A were used as test proteins in untreated fused-silica capillaries in buffers of pH ca. 7.0 and 9.0 The zwitterion-containing buffers were compared with buffers containing high ionic salt concentrations and a buffer containing a combination of high ionic salt and high zwitterion concentrations. Over 100,000 theoretical plates were obtained in less than 30 min. for both test proteins in a pH 7 buffer containing both trimethylglycine and potassium sulfate. The advantages and disadvantages of this technique compared with those of other methods used to prevent protein adsorption are discussed.

Animals↗
PubMed1992

Buffered lidocaine as a local anesthetic: an investigation of shelf life.

STUDY OBJECTIVE: To determine whether buffered lidocaine must be prepared just before use. DESIGN: Randomized, double-blind, prospective trial. SETTING: University hospital. PARTICIPANTS: Twenty-four adult volunteers. INTERVENTIONS: Three buffered lidocaine solutions prepared seven days, one day, and just before use were compared with a control solution. Subjects received 0.5 mL intradermal injections of each solution. Pain of infiltration and extent and duration of anesthesia were measured. MEASUREMENTS AND MAIN RESULTS: Pain of infiltration was less with all buffered solutions than control (P less than .0001). Mean maximum diameter of anesthesia ranged from 29 to 33 mm for the buffered solutions compared with 31 mm for control. Mean duration of anesthesia was 33 minutes for control and 30 minutes for all of the buffered solutions. There was no statistically significant difference in extent or duration of anesthesia for any of the solutions (P greater than .5, beta = .15 for delta = 10%). CONCLUSION: Buffered lidocaine stays effective for up to one week after preparation. It is therefore convenient to use in emergency settings.

Adult↗
PubMed2001

Control of electrochemical reactions at the capillary electrophoresis outlet/electrospray emitter electrode under CE/ESI-MS through the application of redox buffers.

It was found that combining capillary electrophoresis (CE) and electrospray ionization mass spectrometry (ESI-MS) overlays two controlled current techniques to form a three-electrode system (CE inlet, CE outlet/ES emitter, and MS inlet electrodes) in which the CE outlet electrode and the ES emitter electrode were shared between the CE and the ESI-MS circuits. Depending on the polarities and magnitudes of the voltages at the CE inlet, CE outlet/ES emitter, and MS inlet electrodes, the nature of the two redox reactions at the shared electrode was the same or different (both reduction, both oxidation, or one oxidation and the other reduction). Several redox buffers were introduced for controlling electrochemical reactions at the shared electrode. By reacting at this electrode, redox buffers were able to maintain electrode potentials below the onset of water electrolysis, thereby eliminating gas bubble formation and/or pH drift. The volume of the gas generated due to water electrolysis was used to quantitate water oxidation or reduction at this electrode. Two types of redox buffers were used. A reactive electrode with an oxidation potential below that of water was used as the electrode under anodic conditions. Also, a reactive compound with a redox potential below that of water was added to the CE and/or ESI running buffer. When the shared electrode was the anode of both CE and ESI-MS circuits, the use of iron or etched and sanded stainless steel (ss) wire, instead of platinum wire, suppressed bubble formation at the shared electrode. Under these conditions, corrosion of the Fe wire and formation of Fe2+ replaced oxidation of water, eliminating O2 gas bubble and H+ formation. When mixtures of peptides were analyzed, iron adducts of peptides were observed. For a fresh wire, however, the intensities of adduct ions were less than 3% of the protonated molecules. After a few days of operation, the intensities of the adduct ions increased to approximately 50%, due to rust formation on the Fe wire. On-column rinsing with a 40% solution of citric acid rejuvenated the Fe wire and reduced the adduct peak intensities to less than 3%. Unmodified ss wire did not quench bubble formation, which was attributed to its passivated surface. When Fe, ss, and Pt wires were used as the shared electrode under forward polarity CE and positive ESI mode, where the shared electrode acted as a cathode with respect to CE inlet and as an anode with respect to MS inlet, reduction of water at the cathodic end of the electrode and, in the case of ss and Pt wires, oxidation of water at the anodic end of the shared electrode produced a significant amount of bubbles. Under these conditions, however, a buffer containing 50 mM p-benzoquinone completely suppressed both cathodic reduction and anodic oxidation of water for CE currents up to 4 microA. Reduction of p-benzoquinone at the cathodic end of the shared electrode to hydroquinone, and oxidation of this hydroquinone at the anodic end of the electrode, replaced reduction and oxidation of water, eliminating bubble formation. A 0.1% acetic acid solution saturated with I2 was also found to suppress bubble formation at the cathode for CE currents up to 3 microA; however, strong iodine adduct ions were observed under CE/ESI-MS when a mixture of peptides was analyzed. The application of iron as an in-capillary electrode for the analysis of a peptide mixture and a protein digest demonstrated a high separation efficiency similar to when hydroquinone was used as a redox buffer.

Journal Article↗
PubMed2003

Complexation of copper by zwitterionic aminosulfonic (good) buffers.

Copper binding properties were investigated for several popular zwitterionic buffers. The two buffers 4-morpholinoethanesulfonic acid (MES) and 3-N-morpholinopropanesulfonic acid (MOPS) did not bind copper and would be good choices for metal speciation studies within their operational pH range. Conversely, 3-(N-morpholino)-2-hydroxypropanesulfonic acid (MOPSO) was observed to weakly bind copper directly (log Kc 2.02). Moreover, strong copper binding was observed for 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), 4-(2-hydroxyethyl)piperazine-1-propanesulfonic acid (HEPPS), and N-(2-hydroxyethyl)piperazine-N'-(2-hydroxypropanesulfonic acid) (HEPPSO). Log Kc values range from 7.04 to 7.68 and are indicative of strong copper binding ligands. The latter buffer also exhibited weak binding characteristics with a log Kc of 2.05. The strong Cu binding ligands were present in HEPES, HEPPS, and HEPPSO at much lower concentrations than the total buffer concentration. MES, HEPES, MOPSO, and HEPPSO were analyzed by electrospray-ionization quadrapole time-of-flight mass spectroscopy. The most prominent feature of the spectra for each buffer analyzed was the presence of multiple oligomers, indicating a propensity of interaction between buffer molecules. In addition, the presence of several contaminants was identified in the mass spectrum of the HEPES matrix, including a prominent contaminant (at m/z 131) present in levels similar to those obtained from the modeling of the copper titration data. Other contaminants were found in the other matrixes but were not identified as possible copper binding agents.

Journal Article↗
PubMed2004

Elution of propranolol as an ion-pair complex by buffer solutions on C18-silica.

Propranolol (pK(a) = 9.4) was eluted on C(18)-bonded Kromasil, equilibrated with buffer solutions of methanol and water (40/60, v/v) containing a constant concentration of a counteranion (12 mM). Nine different counteranions were studied: Cl(-), I(-), NO(3)(-), SO(4)(2-), CH(3)COO(-), HOOCC(2)H(4)COO(-), (-)OOCC(2)H(4)COO(-), HOOCCOHCOOHCOO(-), HOOCCOHCOO(-)COO(-), and (-)OOCCOHCOO(-)COO(-). The co-cation was K(+) or Na(+). Vacancy perturbations were measured on three concentration plateaus of propranolol hydrochloride, at 1.2, 12, and 24 mM, by injecting 100 microL of a pure mixture of methanol and water (40/60, v/v). Indirect detection of the solvent, the counteranion, the co-cation, and the chloride ion was carried out at 325 nm, a wavelength at which only propranolol responds. In a 1.2 mM propranolol hydrochloride solution, there is a 10-fold excess of counteranions and only a positive perturbation peak, due to the excluded co-cation and eluting before the column hold-up time, and a large vacancy peak, associated with propranolol, were recorded. Association between propranolol and the counteranion in excess determines the retention time of this second perturbation. The hydrophobicity of the complexes increases in the order Cl(-) < CH(3)COO(-) approximately HOOCC(2)H(4)COO(-) < NO(3)(-) < I(-) < HOOCCOHCOOHCOO(-) < (-)OOCC(2)H(4)COO(-) < SO(4)(2-) approximately HOOCCOHCOO(-)COO(-) < (-)OOCCOHCOO(-)COO(-). Propranolol retention is larger in the presence of the trivalent citrate anion than in that of the bivalent citrate, succinate, or sulfate anions. It is larger with these bivalent anions than with any monovalent anion. Equal concentration of propranolol hydrochloride and buffer in the mobile phase reveals five system peaks associated with the five components (solvent, counteranion, co-cation, chloride, propranolol molecules). In contrast with monovalent anions, bivalent anions (sulfate, succinate, citrate) or trivalent anions (citrate) cause a reversal of the elution order of the perturbation peaks of chloride anions and buffer molecules. This confirms a competition between chloride and buffer anions to form ion pairs with propranolol. The retention of the perturbation signal of the buffer increases with increasing anion charge because multivalent anions can bind to several molecules of propranolol. The perturbation measurements demonstrate the influence of the valence and hydrophobicity of the buffer on the retention of ionizable compounds. The inverse method allowed the derivation of the isotherm parameters from the overloaded band profiles of propranolol. These values confirm that adsorbate-adsorbate interactions increase with increasing valence of the anions.

Journal Article↗
PubMed2005

Dissecting reactivity of clerocidin toward common buffer systems by means of selected drug analogues.

The model drug clerocidin (CL) can form covalent adducts with both Tris and phosphate buffers with negative effects on biological activity, even though the latter is considered a largely inert physiological buffer. With the ultimate goal of learning how to control such reactivity and reduce undesired side reactions, we have investigated the influence of the different functionalities of CL on the formation of buffer adducts. For this reason, selected drug analogues were tested for their ability to react with the two buffers and comprehensive information was gained on both thermodynamics and kinetics aspects of these reactions. Two distinctive reactivity modes were readily observed. The first proved to be under kinetic control and involved the reaction of drug carbonyls (especially the aldehyde in C15) with the Tris amino group to form a Schiff base. The second was found to proceed under thermodynamic control through the attack at the oxirane ring of CL by the buffer's nucleophilic groups (amino nitrogen in Tris and oxygen in phosphate). Important relationships between the two modes were noted, thus providing further demonstration that drug reactivity toward buffers cannot be directly predicted from the functionalities that are potentially involved in the initial reaction. On the contrary, as true for almost any structure bearing potentially reactive functionalities, any solid prediction should be based on a deeper understanding of the mutual influence of vicinal groups.

Aldehydes↗