Final answer:
Penicillin is less effective against Gram-negative bacteria due to its complex cell wall structure, which includes a thin peptidoglycan layer and an additional protective outer membrane.
Step-by-step explanation:
Penicillin and its derivatives are less effective at breaking down the peptidoglycan layer of Gram-negative bacteria due to the complex cell envelope structure of these bacteria. Gram-negative cells possess a much thinner peptidoglycan layer compared to Gram-positive cells, and they have an additional outer membrane that is not present in Gram-positive bacteria. This outer membrane, which is attached to the peptidoglycan by murein lipoprotein, contains lipopolysaccharide (LPS) and provides an extra barrier to substances, including antibiotics like penicillin. The presence of this membrane makes the cell wall of Gram-negative bacteria more resistant to the mechanism by which penicillin inhibits transpeptidase and prevents the cross-linking of the peptidoglycan layer, crucial for the bacteria's cell wall synthesis and integrity.