Which of the following statements best explains why alkaloids, despite being generally water-soluble, can have striking pharmacological effects on vertebrate animals?

1
Alkaloids are usually nonpolar molecules that can easily cross cell membranes
2
The protonated form of alkaloids at physiological pH values allows them to interact with various biological targets.
3
Alkaloids bind to water molecules, facilitating their transport across cell membranes. 
4
The water solubility of alkaloids is irrelevant to their pharmacological activity.
5
Question Not Attempted

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