To calculate the net charge of guanine at pH 3.5, consider its pKa of 2.4, which indicates that at this pH, half of the guanine will be in its non-protonated form. As the pH increases above the pKa, more guanine will adopt its basic conformation. The Henderson-Hasselbalch equation can be utilized to account for the relevant acid dissociation constants (Ka) of guanine. Additionally, determining the isoelectric point can provide a simpler method for calculating the net charge. Understanding these concepts is essential for accurate biochemical analysis.