electron transfer agents in oxidation–reduction reactions. Because of the importance of
these macromolecules to drug action and because of their involvement in various dis-
eases (e.g., porphyria), porphyrins are of interest in drug design and medicinal chemistry.
Thealkaloidsare also relevant to drug design. Alkaloids are complex heterocyclic
compounds that contain nitrogen and thus have base-like (hence the term “alkaloid”)
properties; they are extremely structurally diverse. Nicotine is one of the simplest alka-
loids. Oxidation of nicotine produces nicotinic acid, a vitamin that is incorporated into
the important coenzyme nicotinamide adenine dinucleotide, commonly referred to as
NAD+(oxidized form). The neurotransmitter serotonin is an alkaloid containing the
aromatic indole ring system.
8.1.7 MetalsTraditionally, medicinal chemistry and drug design have lain firmly within the domain
of organic chemists, not inorganic chemists. Accordingly, the potential role of inor-
ganic salts and organometallic substances has been relatively neglected. Despite con-
cerns about long-term toxicities, the inclusion of metal atoms into the drug design
repertoire dramatically increases the diversity of atomic building blocks beyond the
time-honoured reliance upon C, O, N, and S. Arguably, the therapeutic potential
of organometallic agents as antitumor and antimicrobial drugs has not been fully
exploited; their potential role as therapies in a wide range of other disorders has been
totally ignored.
8.1.7.1 Classification of Bioactive Metals
Metals that are potentially biologically active, either therapeutically or toxicologically,
may be divided into the following groups, based upon their electron configuration and
position in the periodic table of the elements:
Main group metals
Group 1A—the alkali metals: Li, Na, K, Rb, Cs, Fr
Group 2A—the alkaline earth metals: Be, Mg, Ca, Sr, Ba, Ra
Group 3A—Al, Ga, In, Tl
Group 4A—Sn, Pb
Group 5A—Bi
Transition metals
Period 4 (4s3d4p)—Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn
Period 5 (5s4d5p)—Y, Zr, Nb, Mo, Tc, Ru, Rh, Pd, Ag, Cd
Period 6 (6s5d6p)—La, Hf, Ta, W, Re, Os, Ir, Pt, Au, HgThe main group metals are the most important, given the role of Na+,K+,and Ca^2 +in
bioelectrical excitability. The transition metals also have biological relevance. A formal
definition of transition metals is that they have partially filled dorforbitals in either
their free (uncombined) atoms or one or more of their ions. Transition metals may be
divided into d-block and f-block elements; the f-block is further divided into the lan-
thanide and actinide series. Since f-block metals are not of great significance to medicinal
480 MEDICINAL CHEMISTRY