2.2.3. 2D 1H,13C-HSQC 2D- Heteronuclear Single Quantum Coherence (HSQC) experiments are commonly used to help resolve spectral overlap [139] while providing 13C information without the inherent sensitivity losses involved in 13C direct detection (see below). HSQC shows the correlations between directly coupled nuclei [140], e.g., 1H-13C or 1H-15N [140]. As such, an HSQC spectrum will show clean peaks for each unique proton directly connected to the heteronuclear nuclear atom of interest [140,141]. In 1H,13C/15N HSQC experiments, the magnetization is transferred from the more sensitive nucleus (I:1H) to the less sensitive nucleus (S:13C/15N) [142,143,144] (Figure 3). This is especially useful when applying NMR spectroscopy to drug design, as most drugs are organic (i.e., contain carbon atoms), and the relative abundance of 13C (1.1%) is quite low [143]. By transferring sensitivity from 1H to 13C, one can circumvent the long experimental time required for 1D 13C experiments [143]. For example, De Castro et al. [145] studied Ptac2S and its related cytotoxicity to the cisplatin-resistant epithelial ovarian carcinoma (EOC), Skov-3 cells. In the study, they used NMR spectroscopy and multi-variate statistical analysis to observe how Skov-3 cells reacted to treatment with Ptac2S. In particular, they used 1H,13C-HSQC along with 1H-COSY and Heteronuclear Multiple Bond Correlation (HMBC), and the Human Metabolome Database to assign the chemical shifts of the lipid metabolites present in the studied samples. Interestingly, Skov-3 cells treated with Ptac2S produced more pyruvate than Skov-3 cells treated with cisplatin. The authors also noticed an unexpected difference in lipid metabolite expression levels between the cells treated with Ptac2S and those treated with cisplatin. These results provide a possible explanation for how Ptac2S is able to overcome cisplatin resistance in Skov-3 cells [145].