pH is a tightly regulated physiological parameter that is often altered in diseased states like cancer. The development of biosensors that can be used to non-invasively image pH with hyperpolarized (HP) magnetic resonance spectroscopic imaging has therefore recently gained tremendous interest. Here, we developed a systematic approach to tailor the pK_a of molecules using modifications of carbon chain length and derivatization rendering these molecules interesting for pH biosensing. Notably, amino acid derivatives bear different spin-1/2 nuclei that exhibit a pH-dependent chemical shift in the physiological range and that can be polarized using DNP. ¹³C T₁ measurements of hyperpolarized substances were performed on a Spinsolve Carbon.