Triazine-Substituted and Acyl Hydrazones: Experiment and Computation Reveal a Stability Inversion at Low pH

Condensation of a hydrazine-substituted <i>s</i>-triazine with an aldehyde or ketone yields an equivalent to the widely used, acid-labile acyl hydrazone. Hydrolysis of these hydrazones using a formaldehyde trap as monitored using HPLC reveals that triazine-substituted hydrazones are more labile than acetyl hydrazones at pH >5. The reactivity trends mirror that of the corresponding acetyl hydrazones, with hydrolysis rates increasing along the series (aromatic aldehyde < aromatic ketone < aliphatic ketone). Computational and experimental studies indicate a reversal in stability around the triazine p<i>K</i>_a (pH ∼5). Protonation of the triazine moiety retards acid-catalyzed hydrolysis of triazinyl hydrazones in comparison to acetyl hydrazone analogues. This behavior supports mechanistic interpretations suggesting that resistance to protonation of the hydrazone N1 is the critical factor in affecting the reaction rate

Additional file 2 of Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases

Additional file 2: Table S1. General comparison of immune markers between primary tumors and liver metastases

Additional file 5 of Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases

Additional file 5: Table S2. Comparison of the immune markers of the TC, TF and PT regions

Additional file 1 of Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases

Additional file 1: Figure S1. General comparison of immune markers between primary tumors and liver metastases (A: CD8, B: CD20, C: CD68, D: CD11c, E: VEGFR-2, F: PD-L1, G: Ki67) (p ≥ 0.05, not significant)

Study quality assessment according to the ELCWP Scale.

<p>Study quality assessment according to the ELCWP Scale.</p

Additional file 7 of Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases

Additional file 7: Figure S4. Comparison of the three immunotypes according to the degree of CD8 infiltration. A: Comparison of the three immunotypes at the front of the tumor (CD68, Foxp3, PD-L1 and Ki67). C: Comparison of the three immunotypes at the center of the tumor (CD68, Foxp3, PD-L1 and Ki67). (*p< 0.05, p ≥ 0.05, not significant)

Forest plot for the association of p-STAT3 expression with lymph node metastasis in colorectal cancer patients.

<p>Forest plot for the association of p-STAT3 expression with lymph node metastasis in colorectal cancer patients.</p

Additional file 3 of Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases

Additional file 3: Figure S2. Representative multiplex immunofluorescence images of 6 cell markers from panel 1 in the tumor center (TC), tumor invasive front (TF), and peritumoral (PT) regions of primary tumors and liver metastases

Additional file 4 of Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases

Additional file 4: Figure S3. Representative multiplex immunofluorescence images of 6 cell markers from panel 2 in the tumor center (TC), tumor invasive front (TF), and peritumoral (PT) regions of primary tumors and liver metastases

Subgroup analysis of p-STAT3 expression and clinicopathological feature of colorectal cancer.

<p>Subgroup analysis of p-STAT3 expression and clinicopathological feature of colorectal cancer.</p