Acid-base catalysis of N-[(morpholine)methylene]daunorubicin

Abstract

The stability of N-[(morpholine)methylene]-daunorubicin hydrochloride (MMD) was investigated in the pH range 0.44−13.54, at 313, 308, 303 and 298 K. The degradation of MMD as a result of hydrolysis is a pseudo-first-order reaction described by the following equation: ln c = ln c₀ – k_obs. t. In the solutions of hydrochloric acid, sodium hydroxide, borate, acetate and phosphate buffers, k_obs = k_pH because general acid-base catalysis was not observed. Specific acid-base catalysis of MMD comprises the following reactions: hydrolysis of the protonated molecules of MMD catalyzed by hydrogen ions (k₁) and spontaneous hydrolysis of MMD molecules other than the protonated ones (k₂) under the influence of water. The total rate of the reaction is equal to the sum of partial reactions: k_pH = k₁ • a_H+ • f₁ + k₂ • f₂ where: k₁ is the second-order rate constant (mol⁻¹ l s⁻¹) of the specific hydrogen ion-catalyzed degradation of the protonated molecules of MMD; k₂ is the pseudo-first-order rate constant (s⁻¹) of the water-catalyzed degradation of MMD molecules other than the protonated ones, f₁ – f₂ are fractions of the compound. MMD is the most stable at approx. pH 2.5.

Keywords::

• N-[(morpholine)methylene]daunorubicin
• HPLC
• stability in aqueous solutions