An innovative and sustainable adsorption-assisted isomerization strategy for the production and simultaneous purification of high-purity lactulose from lactose isomerization

Abstract

The production of lactulose via aldose-to-ketose chemo-catalytic isomerization of lactose exhibits an unfavorable equilibrium with a thermodynamically-limited yield. Isolation of high-purity lactulose from lactose-containing mixtures presents another challenge due to their high structural similarity. Herein, we present an innovative and sustainable adsorption-assisted isomerization strategy based on molecular recognition with phenylboronic acid (PBA)-functionalized adsorbent (PBA-adsorbent) for combined adsorption-assisted isomerization and simultaneous purification of lactulose. The applied macroporous PBA-adsorbent exhibited high lactulose adsorption capacity (~120 mg/g) with excellent lactulose selectivity (>80%), regardless of the lactulose-to-lactose ratio within a practical range (≥1:9). Through a typical pH-controlled two-stage sequential desorption process, the adsorbed lactulose could be recovered in an acidic solution (0.1 M HCl) as a pure (purity > 95%) and concentrated lactulose stream (12.13 g/L), with a recovery ratio of over 90%. To further improve the lactose-to-lactulose isomerization efficiency, the PBA-adsorbent-dominated adsorption-assisted strategy was investigated. Through batch- or in situ selective binding of the newly formed lactulose catalyzed by Na2HPO4 + NaOH, the isomerization equilibrium was significantly improved and the net results showed enhanced lactulose yield of up to ~51% with limited byproduct formation. Notably, both the PBA-adsorbent and the alkaline solution could be reused and recycled, and the structure of the PBA-adsorbent remained unchanged after being regenerated and reused multiple times. A possible mechanism involving pH-responsive activation, selective-competitive binding, and sequential desorption-regeneration is proposed to explain the high-efficiency of adsorption-assisted isomerization. For the first time, our results validate the potential of the applied adsorption-assisted isomerization strategy to simultaneously isomerize and isolate high-purity lactulose.