How It’s Made: the Drug Discovery Edition

Medicine, drugs, remedies–whatever you call them, they are a necessary part of 21st century society, and each and every one of them has been discovered or synthesized through a series of reaction. Previously, we have talked about specific drugs, specific structures, and what they did individually, and now, we’re going to tell you why it all works.

Many of the drugs that you take on a daily basis are not naturally occurring, and so they have to be synthesized in a lab through a series of reactions.Many of these reactions include the creation of chemical structures through the combination of molecules at certain places. But I can hear you asking, “Why does it bond together?” Here’s why…

Organic Chemistry and Thermodynamics and Kinetics

This image shows the structures of diamond and graphite.In chemistry, molecules bond with each other if the conditions are thermodynamically favorable, or in other words, if the change in Gibb’s free energy is negative and the reaction is therefore spontaneous. When talking about synthesis for reaction that are spontaneous, it is also extremely important in pharmacology to consider the kinetics of the reaction. There may be a way to create a life-saving drug through one, spontaneous reaction, however if the reaction is kinetically extremely slow, there will never be enough to create a viable amount of the drug. Thus, in drug synthesis, it is important to consider variables that will increase the rate of reaction such as temperature, pressure, and using catalysts. To help visualize this, think of diamonds: the reaction of the crystal turning into graphite is spontaneous, because graphite is a more stable state, but it happens so slowly that you never notice it happening to your own jewelry. So, when creating a drug, developing a reaction is not all that there is to think about.

However, that step is also very important, especially when thinking about how much energy is needed to create the compound, whether or not it would form properly, and if the reverse reaction would be spontaneous if the forward reaction is not. In addition, when considering the reaction itself, it is necessary to consider the chemical structure of the compounds, and how they would bond together. For this, it is necessary to consider their organic chemistry of the compounds, and how they would bond to create the lowest possible energy state for the highest stability. Thus can be done by considering resonance structure, orbitals, bonds, and electron configurations. This is significant because the molecules will form the most stable compound with the lowest potential energy, which in some cases may not be the intended structure.

This shows the reaction for the synthesis of the Quinoline Ring, indicating the structure with the lowest potential energy and thus the most stability.

Intermolecular Forces and Kinetics

When talking about drugs, it is imperative to consider the human body, or whatever body the drug is going into, and the molecules that are in that body. The first main thing to consider is the intermolecular forces between the molecules in the drug and the the molecules in the body. As there will always be London Dispersion forces, and those are dependent on size, it is not as significant as Hydrogen bonding and Dipole-Dipole forces. These forces may impact how the  drugs spread throughout the body, especially with certain enzymes and proteins. Kinetics within the body is also extremely important, because aspects such as the rate of reaction with a certain molecule or organism is important to how concentrated the drug will be, the dosage, and how fast it This is a graph for the half life of a compound, showing the relative time and amount of intended to work. Also, with kinetics, the half-life of drugs is very important to the parameters of the drug, because depending on the drug, it could be able to stay in the body for weeks or longer because of a very long half life, or have been processed by the body within a matter of hours. One example where this is important is with antiretroviral medications given to patients with HIV. These medications must be taken very often because they have very short half lives and are digested by the body at a very high rate, so in response researchers are trying to develop a drug with a much longer half life so that the drug can be taken much less often and will become a sustainable solution.


Electrochemistry is very important in the development of drugs, both for synthesis and for gathering information on different parameters and properties. Some specific examples where electrochemistry is used in research is the investigation of reactive oxygen species, the biooxidative and bioreductive activation of pro-drugs, and DNA alkylation. As for the synthesis, electrochemistry is a widely known and widely used method to create certain physiologically active compounds.

The StruggleThese statistics show the increasing costs of creating new drugs.

The struggle in the synthesis of new drugs is forming an initial reaction that would actually occur. This takes place even before the laboratory, by chemists who research different molecules and how they can be broken and form new bonds with other molecules. In many cases, certain molecules with key structures such
as those mentioned before (beta-lactam ring and quinoline ring) must first have certain bonds broken in order to bond with another molecule at another place. The second task is to find a reaction such that the formation or breaking of bonds at certain places is thermodynamically viable so that the reaction will occur. The next part of this is done in a lab, to test the reaction, to measure its kinetic properties, and to see if the creating of the therapeutic molecule is capable of commercial viability. From there, there are countless reactions that were not planned for which may cause fatal reactions in animal models which make the drug unsuitable for human consumption.

According to recent statistics, only 1 out of 5,000 drugs which are initially created in a preclinical setting are approved by the Food and Drug Administration to come onto the market, making the cost of creating new drugs astronomically high. Not only does this hinder the drug companies, but also the people who buy these expensive medicines. That, is the pharmacological struggle.

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