Time-programmable pH: decarboxylation of nitroacetic acid allows the time-controlled rising of pH to a definite value†

In this report it is shown that nitroacetic acid 1 (O2NCH2CO2H) can be conveniently used to control the pH of a water solution over time. Time-programmable sequences of the kind pH1(high)–pH2(low)–pH3(high) can be achieved, where both the extent of the initial pH jump (pH1(high)–pH2(low)) and the time required for the subsequent pH rising (pH2(low)–pH3(high)) can be predictably controlled by a judicious choice of the absolute and relative concentrations of the reagents (acid 1 and NaOH). Successive pH1(high)–pH2(low)–pH3(high) sequences can be obtained by subsequent additions of acid 1. As a proof of concept, the method is applied to control over time the pH-dependent host–guest interaction between alpha-cyclodextrin and p-aminobenzoic acid.


Content
Experimental Methods S1 Simulated kinetics of 0.010 M NaOH solution added with 1 equiv. of nitroacetic acid 1 S3 Simulated kinetics of 0.010 M NaOH solution added with 2 equivs. of nitroacetic acid 1 S5 Kinetic runs obtained adding 0.015 M acid 1 to 0.0075, 0.015, 0.030 and 0.050 M NaOH S8 pH Monitoring of the Reaction between 0.015 M NaOH and 0.030 M 1 with argon or air bubbling S9 pH Monitoring of the Reaction between 0.010 M NaOH and 0.020M 1 without argon bubbling S9 Decarboxylation followed with bromocresol green S10 Decarboxylation followed with methyl red S11 Three pH 1(high) -pH 2(low) -pH 3(high) sequence triggered by three subsequent fuel pulses without restoring the initial pH (12) after the first two pulses. S12 A control experiment S13 Comparison between the fluorescence emission vs time profiles of 0.0050 mM 7 during the decarboxylation of 2.0 mM 1 triggered by 1.0 mM NaOH in the presence or absence of 6 S14 Electronic Supplementary Material (ESI) for Chemical Science. This journal is © The Royal Society of Chemistry 2021 S1

Experimental Methods
All the commercially available reactants were used without further purifications. Nitroacetic acid 1 was obtained following a literature procedure. 1 NaOH and NaCl solutions were prepared using Milli-Q water produced by a Direct-Q3 Millipore apparatus (MERCK KGaA, Burlington, MA, USA) and bubbling argon in the vessel for 15 minutes before use. Nitroacetic acid 1 stock solutions were prepared just before use dissolving 2-20 milligrams of 1 in the proper volume of doubled distilled water, and handled quickly to prevent undesired decarboxylation. All the experiments were carried out at 20°C in a 4 mL (or 8 mL) vial equipped with a capillary connected to a gas cylinder to ensure argon bubbling into the solutions during the measurements. pH was monitored over time with a glass microelectrode 52 08HACH (Ag/AgCl) connected to Crison pH 25+ pHmeter. The final NaCl concentration was always 0.500 M.

Decarboxylation experiments
Decarboxylation kinetics were carried out on a total volume of 2.0 mL. Firstly, the proper volume of 1.00 M NaOH was added to a NaCl solution. Then, the first point was recorded. Eventually, the proper volume of a freshly prepared, concentrated stock solution of nitroacetic acid 1 was added to obtained 2.0 mL of solution with the required concentrations of the components (t = 0). pH variation as a function of time was recorded by reading the pH value on the pH screen at the corresponding time. All the measurements were highly reproducible (repeated three or four times).

Fluorescence measurements
Fluorescence emission kinetics were recorded at room temperature (T = 20°C) on a Horiba Jobin-Yvon FLUOROMAX 4spectrofluorometer (Kyoto, Japan). All collected data were corrected by means of a built-in program in order to counterbalance the decay in sensitivity in the near infrared region and divided by the corrected reference detector. Fluorescence experiments were carried out on solutions with optical density lower than 0.10 to minimize the inner filter effect; samples were prepared immediately before the fluorescence measurements in a quartz cuvette with a 1 cm pathlength.

Decarboxylation kinetics in presence of 6 and 7
Decarboxylation kinetics in the presence of p-aminobenzoic acid 7 and alpha-cyclodextrin 6, were followed simultaneously by means of the pHmeter and the spectrofluorometer. In a 8.0 mL vial, equipped with the microelectrode connected to the pHmeter, the proper amounts of NaOH (stock solution 1.00 M), 7 and 6 were added to a NaCl solution, to give a volume of 5.8 mL. Then, 2.9 mL of the 5.8 mL were transferred into a quartz cuvette lodged inside the spectrofluorometer holder and the pH and fluorescence measurements were started, the former in the vial and the latter in the cuvette. The above kinetic run was also carried out in the absence of 6 . The related pH and fluorescence vs time profiles (red and orange, respectively) are reported in Fig. S11. Kinetics were simulated with the program COPASI 18 by assuming that all the equilibria in Scheme 1 are much faster than the process of decarboxylation, and that the concentration of CO 2 in solution remains fixed to its saturation value throughout the simulated experiment. In Table 1 are summarized the kinetic and equilibrium constants used for the simulation.

S4
In Fig. 1a is reported the plot of pH vs. time when 1 equiv. of nitroacetic acid 1 is added to a solution of 0.01 M NaOH at time t = 0. The kinetics of nitroacetic acid 1, the monoanion 2, and the dianion 3 for the title experiment are reported in Fig. S1.  Kinetics were simulated with the program COPASI 18 as described in previous section.
In Fig. 1b is reported the plot of pH vs. time when 2 equivs. of nitroacetic acid 1 are added to a solution of 0.01 M NaOH at time t = 0. The kinetics of nitroacetic acid 1, the monoanion 2, and the dianion 3 for the title experiment are reported in Fig. S4. The kinetics of carbon dioxide, hydrogencarbonate ion, and carbonate ion for the title experiment are reported in Fig. S6. . When NaOH is in defect (black) or equimolar (red) to acid 1, a sigmoidal and monotonical increase to a plateau value is obtained as expected. When NaOH is in excess (green and blue), addition of acid 1 rapidly lowers a little the pH solution. In the latter cases, lowering of pH is due both to the rapid formation of monoanion 2 which quickly decarboxylates to 4 and to the rapid formation of dianion 3. Indicator colors in function of pH: Three pH 1(high) -pH 2(low) -pH 3(high) sequence triggered by three subsequent fuel pulses without restoring the initial pH (12) after the first two pulses. In both samples the initial pH was set to 11.0 (1.0 mM NaOH). At t =4 min, to the initial solutions (2.90 mL), 0.100 mL of the stock solution of 1 were added. Then, the variations of fluorescence emission were monitored for further 80 minutes. In one case (blu trace), at t =84 min the pH was reset to 11.0 by adding NaOH 1.0 M, in the other case (orange trace), at t =84 min the required small volume of a concentrated stock solution of 6 was added.