Final answer:
Polar substances and charged ions like sodium and potassium generally fail to cross cell membranes without assistance, unlike small nonpolar molecules like O2 and CO2 that can pass through passively.
Step-by-step explanation:
The substances normally prevented from crossing cell membranes under any circumstances are polar substances and charged ions, such as sodium, potassium, calcium, and chloride. These molecules cannot easily pass through the lipid bilayer of the plasma membrane due to their polarity or charge. Additionally, large molecules typically cannot diffuse across cell membranes without assistance. Small nonpolar molecules like oxygen (O2) and carbon dioxide (CO2), however, can passively transport across the membrane without the cell expending energy because they are lipid-soluble and can easily diffuse through the hydrophobic interior of the lipid bilayer.