Chemistry of Antibiotics: Cell Wall Synthesis


In this post we will continue our exploration of the chemistry of antibiotics with a look at drugs that interrupt wall synthesis and how bacteria develop resistance to these drugs.

The target of these antibiotics is crucial because it explains how antibiotics can attack bacteria without affecting human cells. Bacterial cells, unlike animal cells, have cell walls. Therefore, a drug that attacks cell walls will not be able to impact human cells. Bacterial cell walls are essentially a peptidoglycan layer that is composed of units of peptides (proteins) and glycans (sugars). This layer is the primary and most important component of the cell wall.

β-lactam Antibiotics

The most common class of antibiotics that interferes with cell wall synthesis are the β-lactam antibiotics, which

include penicillin. These types of antibiotics function by impeding the synthesis of the peptidoglycan of the bacterial cell wall. There are multiple ways to inhibit the synthesis of the peptidoglycan layer but the most common is by means of destroying the enzymes that do so. If the antibiotic does not function by destroying synthetic enzymes, it could also destroy the enzymes that convert the polymers into a layer of the cell wall. β-lactam antibiotics inhibit cell wall synthesis by preventing the assembly of the peptidoglycan layer. This is done when the antibiotic competes with the polymer at the site of binding.

This video gives a general overview of how peptidoglycans are inhibited by the mechanisms of a beta-lactam antibiotic:

 The Chemistry of Penicillin


Penicillin is one of the most common β-lactam antibiotics, and is characterized by three structural requirements: one fused β-lactam structure, a free carboxylic acid group, and one or more substituted amino acid side chains. Penicillin’s structure prevents the cross linking of peptide chains – weaker cell walls will allow water to flow into the cell freely and the cell will swell and burst, causing cell death. If you change the side R-group chain on the penicillin, the penicillin can possess different properties, such as acidity or penicillinase resistance.

The β-lactam ring in the penicillin reacts with an enzyme that is used for building the cell wall called DD-transpeptidase. Resemblances between a segment of the penicillin structure and the backbone of a peptide chain of the bacterial cell wall have been used to explain the mechanism of beta-lactam antibiotics.

Bacteria Fighting Back

Bacteria have a number of ways to evolve and beat our human antibiotics. One method that bacteria employ in order to fight drugs that interrupt cell wall synthesis, is changing the structure of their cell walls. One instance of this is mutation of pathogenic bacteria. Bacteria that colonize the mucosal pathways, such as nostrils, lips and eyelids, must undergo changes in order to avoid the antimicrobials of the host. In particular, they must avoid lysozyme, an enzyme that destroys the cell walls of bacteria. The activity of lysozyme is similar to β-lactam antibiotics since they both attack the cell walls of bacteria. Since the muramidase activity of lysozyme leads to hydrolysis of the β-1,4 glycosidic bond between the C-1 carbon of N-acetyl muramic acid (MurNAc) and the C-4 carbon of N-acetylglucosamine (GlcNAc), that is the bond that the bacteria have to change in order to survive.Streptococcus pneumoniae and bacillus anthracis, two lysozyme resistant bacteria, have peptidoglycan cell walls that are N-deacetylated, which means that the composition and structure of the sugar component of the cell wall is changed. It was shown that N-acetylating them caused them to be more susceptible to lysozyme. Therefore, it was concluded that N-deacetylating the caused lysozyme resistance. This shows that through changes in structure, bacteria can evade agents that inhibit their cell wall synthesis. When this happens, we too must evolve and change our tactics. This is why new drugs always need to be developed. Bacteria develop resistance, and we must develop new antibiotics.

Want to know more about different classes of antibiotics that inhibit cell wall synthesis? Check out thislink to learn about glycopeptide antibiotics. Of course that’s not enough to satisfy the hunger of your mind, so here is a website that goes further in-depth regarding the processes of cell wall synthesis.

Local Anesthetics: The Caine Family

As seen in the previous post, local anesthetics generally work to prevent only a small area of the body from experiencing pain by inhibiting the flow of sodium ions (preventing action potential thus preventing nerve activity) through sodium channels embedded in the cell membrane of neurons. More specifically, the local anesthetic will bind to a receptor inside the sodium channels and antagonize it, therefore closing the sodium channels thus creating the halt in the influx of ions through the channels as seen in the diagram below.


Many local anesthetics commonly bind to the N-methyl-D-aspartate (NMDA) receptor (an image of how the anesthetic might bind to a receptor through the polar attractions between the receptor and anesthetics is shown here), such as the constituents of the Caine family: a category of local anesthetic compounds that share similar qualities (i.e. similar receptors and mechanism of actions) and end in the suffix “caine”. The following will consist of descriptions of three different local anesthetics, particularly from the Caine family, to demonstrate the functional and molecular diversity in the compounds of local anesthesia.


Cocaine, otherwise known as benzoylmethylecgonine, can be used as a type of local anesthetic, but for the past several decades it has reached the headlines for different reasons. Cocaine was used historically as an eye and nose anesthetic, used to block nerve signals during surgery, but side effects of cocaine exposure during surgery include intense vasoconstriction and cardiovascular toxicity. It is a powerful nervous system stimulant, and above all, it is extremely addictive. Repeated use of the drug can cause strokes, cardiovascular disease, and several hundred other afflictions such as gingivitis, lupus, and an increased chance for heart attacks. Cocaine can be administered in many different ways, most commonly through insufflation, injection, and in the case of crack cocaine, inhalation. Cocaine is a controlled substance around the world due to its addictive properties and terrible side effects of constant use.

How To Use It:

Most users of pure cocaine are drug addicts, but cocaine hydrochloride is still used as a topical anesthetic. It is applied through the mouth, or the nose using a cotton swab to numb the area. It should not be used in the eye or injected, and rarely, addictive behavior will be expressed by the patient. Use the medication as specified by a healthcare professional, and do not use more frequently or longer than specified.

Molecular Structure:

Cocaine usually contains pure C17H21NO4 from the leaves of the coca plant.]

2D structure                                              3D structure


  • The molecular weight of cocaine is 303.35 g/mol.
  • The molecular formula is C17H21NO4
  • The systematic name is Methyl (1R,2R,3S,5S)-3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
  • Approximately 35.9 million Americans aged 12 and older have tried cocaine at least once in their lifetime, according to a national survey, and about 2.1 million Americans are regular users

Novocain (Procaine):

First synthesized in 1905, novocain (the trade name of procaine) is an ester-type local anesthetic that is able to induce a loss of sensation when injected, as opposed to oral intake which has been stated to wield therapeutic values. The first synthetic local anesthetics to be produced, novocain was primarily utilized for oral surgeries in dentistry however due to ester-type anesthetics having generally a high potential of causing allergic reactions, it eventually became obsolete and eventually replaced by a more effective anesthetic known as lidocaine. Ester-type anesthetics are more prone causing allergic reactions compared to Amide-type anesthetics because when they metabolize in the body, they form a compound known as para-aminobenzoic acid (PABA). PABA has a documented history of causing allergic reactions that range from urticaria to anaphylaxis. Generally, the adverse side effects of using novocain include heartburn, migraines, nausea, and can induce a serious condition known as systemic lupus erythematosus (SLE), therefore it is highly advised that intake is performed by a healthcare professional. However, novocain also retains the property and advantage of constricting blood vessels, reducing bleeding unlike many other local anesthetics.

How To Use It:

The common and primary method of intake of novocain for its anesthetic properties is through injection in solution state. However, if novocain is present in capsule or tablet form, oral ingestion can also performed though its properties and effects will be greatly mitigated and may induce therapeutic rather than anesthetic conditions.  An informative video of how novocain is administered in oral surgeries of dentistry can be found  below.

Molecular Structure:

Novocain contains pure C13H20N2O2.

2D structure                            3D structure


  • The molecular weight of novocain is 236.31 g/mol.
  • The molecular formula is C13H20N2O2.
  • The systematic name is 2-(diethylamino)ethyl 4-aminobenzoate
  • The melting point of novocain is approximately 61 °C while its pKa value at 15 °C is 8.05



Tetracaine is a type of local anesthetic and it is used as a numbing medication. It is generally used for surface and spinal anesthesia and it works by blocking the nerve signals in your body. There most used type of tetracaine medication is cream and ointment. It’s primary use is to reduce pain or discomfort caused by minor skin irritations, cold sores or fever blisters, sunburn or other minor burns, insect bites or stings, and many other sources of minor pain on a surface of the body. The reason why this medication is given is to lessen the pain caused by the insertion of a medical instrument such as a scope or a tube. Although in most situations tetracaine is used on the skin, it can also be used on the eye. This eye medication is in the form of drops and it is used to decrease the feeling in your eyes right before going through surgery or perhaps a test or procedure involving the eyes.

How To Use It:

The eye drops medication should be issued by the clinic and after going through the procedure, the patient must refrain from touching his or her eye until the medication is no longer in effect and in some cases, an eye patch is required. The Tetracaine topical gel is applied by very small amounts only necessary to cover the area and should not be used more than four times a day unless the doctor specifies otherwise.

Molecular Structure:

Tetracaine contains more than 98 percent of .C15H24N2O2  calculated on the dried basis..

2D structure                                                      3D structure


  • The molecular weight of tetracaine is 264.36 g/mol.
  • The molecular formula is C15H24N2O2.
  • The systematic name is 2-(dimethylamino)ethyl 4-(butylamino)benzoate.
  • The boiling point of tetracaine is between 362.4 degrees Celsius and 416.4 degrees Celsius at the standard 1 ATM.

Problems Arise: Balloons are Inflating the Helium Shortage


              It sounds ridiculous to think that something used everyday in birthday parties is in a serious shortage, but helium, an element used in applications ranging from balloons to MRI scanners, is now getting very difficult to find.  That means that very soon, your cousin may have a very disappointing birthday party. Yet that is the least of our problems.

              The most surprising thing about this shortage is that helium is the second most abundant element in our universe.  However, most of this helium is, practically speaking, way out of our reach.  Let’s embark on an exploration of helium to see why it is so hard to find, what Helium does for us, and what we can do in the future to make the search for it a little easier.

              The main trouble that arises when trying to obtain helium is that it’s less dense than air. This means that any helium trapped under the Earth’s surface eventually diffuses into the atmosphere. Once it’s in the air, it’s out of reach; we have yet to create a feasible means of collecting all of this diffused helium.  Currently, a huge build-up of Helium-4 (He-4) is being released in Yellowstone and about 60 tons of helium are released every year.  Some of this helium is diluted into the atmosphere, but the rest of it escapes the atmosphere into space.  Although it seems like we are letting this helium go to waste, there is just simply no viable way to collect it.

                                                                   yellowstone He.jpg                                                                                                                                                   Yellowstone National Park

              Yet there are other factors that contribute to Helium’s shortage. For one, the production of Helium as a by-product of nuclear decay is not a heavily invested means of production. This is largely because it is not an economically viable option (along with capturing the diffused Helium in the air as mentioned before); however as we will see, the value of Helium just may be priceless.  Another factor contributing to the shortage is the fact that in the past few decades, the demand and use of Helium has skyrocketed, largely ascribed to our squandering ways. With a limited amount, prices of Helium have soared as well.

              So why exactly is helium important anyway?  Helium has a multitude of applications, but its main application is its use to cool superconducting magnets in MRI (magnetic resonance imaging) scanners. Superconducting magnets are magnets that can produce immense magnetic fields, which MRI scanners require to operate and use to construct images of the body. MRIs use superconducting magnets because below a certain temperature, known as a critical temperature, a metal loses its resistance (The reason this happens at low temperatures is because there are lower energy and less frequent atomic collisions). This temperature needed for superconductivity requires cryogenic temperatures.  That’s where helium comes in.  Liquid helium, due to its extremely low (4.2 K) boiling point and high thermal conductivity, is very efficient at capturing heat and is the only medium that can induce superconductivity in metal alloys. In MRI scanners, the wires are bathed in liquid helium at -269.1 °C to capture heat and remove it from the system. This effectively removes the wires’ resistance and allows them to become superconductors. However, a normal MRI scanner uses 1,700 liters of helium which periodically has to be changed. This is a huge amount of helium, especially with the impending shortage. A new method of superconductor cooling was recently developed by a company known as Cryogenic. This method uses a significantly lower amount of helium and may soon significantly reduce the amounts of helium that we waste.


                                                                                 MRI Scanner

              Another important application of helium is its use in oxygen tanks for underwater diving.  Normally air is comprised of approximately 20% oxygen gas and 80% nitrogen gas. Nitrogen gas is a lot more soluble than Helium, and is especially soluble at high pressures – which essentially keeps the gases in solution. The difference in solubility between the two plays a key role in why Helium is used, and is due to their difference in size. In order to dissolve any substance into a solvent, the solute and solvent must have interactions with one another. For non-polar gases like N2 and He, it becomes difficult to create the interactions with polar water molecules. To actually bring one of these gases into solution, an induced dipole must be created in the gas. An induced dipole becomes increasingly easier as the molar mass of the substance increases. This is because there are then more electrons to shift between the atoms thereby creating a strong bond between the solute and solvent. Between N2 and He, nitrogen gas clearly dominates in molar mass and strength of LDF forces. So at these high pressures below the water, the nitrogen gas becomes highly soluble in the bloodstream inducing nitrogen narcosis, a state with similar effects to those of alcohol. Furthermore, as divers begin to rise from the water, the solubility of nitrogen decreases and begin to bubble out of solution (the blood). This is extremely dangerous as it can create bubbles in the bloodstream which wouldn’t be able to pass through fine capillaries in the body. The condition, called the Bends, is life threatening. To prevent this from happening, Helium is used. As stated previously, Helium is less soluble than Nitrogen, so less Helium would get into the bloodstream. Furthermore, Helium is an inert gas, so its narcotic properties are negligible and do not pose any problems of toxicity like Nitrogen does. Helium continues to be the most ideal gas for diving tanks, and the shortage poses a serious threat to the maritime industries.

              With such versatility it seems more likely that the United States will take on currently, non-viable means to produce Helium rather than drastically cut down on usage. There will likely be 3 primary sources that will serve the United States in the future as a source of Helium. As stated before the first source would be through nuclear reactions.  One reaction that results in a formation of a helium atom is plutonium decomposition (Pu-239).  A plutonium nucleus decays into an alpha particle and a uranium nucleus.  The alpha particle immediately captures 2 electrons from the nearby plutonium metal and becomes a helium atom in the midst of a plutonium lattice.  There are 2 main problems with this method of producing helium.  Firstly, this process has a half-life of 24,100 years.  Using the half-life formula for first-order reactions, one could calculate k to be (ln2)/t1/2 = (ln2)/24,100= 2.88 x 10-5.  Using the first-order integrated rate law, one could determine that in a year, 10,000 g of plutonium will decompose to 10,000 x e-2.88×10^-5 = 9,999.71 g.  Therefore, in a year, 10,000 g of plutonium will only decompose to 0.29 g of decay.  That’s a measly 0.0029% decay after an entire year.  This makes generating a profitable amount of helium unfeasible to say the least.  The second problem with this method is that once the helium is produced, it is stuck in the plutonium lattice.  This makes it become very difficult to isolate and extract

              The second source is actually through natural gas. Some natural gas contains amounts of Helium that can be extracted through a complicated process. The reason it is not widely used today is because the extraction process requires strict criteria and many samples of natural gas only contain about 0.3-1.9 percent Helium by volume. Furthermore, there are many economic considerations before uptaking such a project as the extraction process requires facilities. However, in essence there are 3 steps to the extraction process. The first step is to remove the impurities from the natural gas such as water, carbon dioxide and hydrogen sulfide through means such as amine and glycol adsorption. The second step is to extract the high molecular-weight hydrocarbons. Finally, through cryogenic processing the remaining methane gas is extracted. This works because Helium has the lowest freezing point of any element. So as the temperature is sufficiently reduced, all other substances will freeze and can be filtered out. What’s left is crude Helium, containing approximately 50-70% Helium and the rest is Nitrogen gas and other traces of gases. To further purify the Helium to approximately 99.99% purity, Pressure-Swing Adsorption (PSA) is used. PSA separates different gases from each other based on the premise that each gas has a different affinity for different adsorbent materials, and have different vapor pressures. Due to the varying vapor pressures, one gas can be completely transformed into the gas phase at one temperature and pressure and then extracted, while the other gas would remain largely as a liquid.

                                        adsorption.png                                                                                                     Pressure Swing Absorption Process

              The final source will actually be where Helium is most abundant: outer space. Observations from lunar missions have concluded that there are about 22 grams of helium in every cubic meter of lunar soil. In the future, if Helium were to ever run dry on Earth, this alternative would likely create a madman’s dash to the Moon in search of this precious yet scarce gas.

              In essence, our lavish uses of Helium without a steady state of supply has caused a shortage that affects many scientific disciplines that rely on the unique characteristics of Helium. As a human race, we must either cut down on our uses of Helium in some shape or form, or begin taking measures to create more Helium for use in the future. Without Helium, many of the opportunities and technology today will float adrift tomorrow, just an arm’s length away from humanity’s struggling grasp for the resources we use so plentifully.

Synthesis of Antibiotics

     Antibiotics are agents that are used to kill microorganisms or inhibit their growth. They can either occur naturally or can be synthetically produced. Extremely common today are semi-synthetic modifications of natural compounds. These chemical, biosynthetic antibacterial compounds are classified according to their biological effect on microorganisms. Bactericidal agents kill bacteria altogether while bacteriostatic agents slow down or stall bacterial growth. One specific semisynthetic antibiotic is what is known as Erythromycin.

     Erythromycin is what is considered a macrolide antibiotic. Macrolide antibiotics slow the growth of and often kill sensitive bacteria by reducing the production of important proteins needed by the bacteria to survive. This drug is notorious for being similar to penicillin in what it is used for and how it is synthesized. Often it is used as a substitute for people who are allergic to penicillin being that penicillin is such a common allergy. It is commonly used to treat respiratory tract infections, acne, Gonorrhea, Chlamydia, and other STDs. It is also applied to the eyes of newborn babies in order to prevent ophthalmia neonatorum. Erythromycin works by improving gastric emptying as well as its symptoms, though oral use of this drug is generally for short term use rather than long term.

     The chemical structure of Erythromycin, C38H69NO12, is extremely complicated and elaborate. Its synthesis published by Robert B. Woodward in 1981, the drug consists of a 14-membered lactone ring along with ten asymmetric centers and two sugars, L-cladinose and D-desosamine. The compound’s complexity makes it extremely hard to produce synthetically therefore it is produced by the bacterium Saccharopolyspora erythraea. Synthesis of this drug includes an intricate series of reactions. Reactions include hydrolysis and stereospecific aldolization. Oxidations and reductions are also involved in the synthesis by the pure enone’s conversion to desired dithiadecalin product. This product is further converted to ketone as well as an aldehyde. Overall, the synthesis contains roughly 50 steps split into 4 parts.

     Erythromycin comes in 4 forms: Erythromycin A, B, C and D. Erythromycin A is known for being the most antibacterial, with B, C and D following respectively. As discussed previously, this drug is considered to inhabit bacteriostatic activity, otherwise it inhibits growth of bacteria rather than stopping it or killing in completely. Its bacteriostatic capability is most displayed at high concentrations by interfering with aminoacyl translocation. This process objects to the functionality of important proteins, which is overall how antimicrobial action is put in place. One should be aware of the side effects erythromycin may cause, for example, abdominal pain, nausea, diarrhea, and vomiting.

     Zithromax is a semi-synthetic antibiotic, an example of the subclass, azalides and slightly differs in structure from the classical macrolides. It is used to treat and prevent infection within an area thought to be caused by bacteria. Like all other antibiotics, zithromax has an active ingredient, which in this case is azithromycin, a subclass of macrolide antibiotics. Azithromycin is derived from erythromycin but differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring and is has improved activity through its glycosylated side chains. In this form, it has a molecular formula of C38H72N2O12. However, when Azithromycin is a dihydrate, which means it contains two molecules of water or its elements, it has a molecular formula of C38H72N2O12*2H2O. Also, Azithromycin contains inactive ingredients such as pregelatinized starch, lactose, sucrose, sodium phosphate, hydroxypropyl cellulose, or xanthan gum that all supplement the active ingredient.


     Azithromycin binds to 50s ribosomes and interferes with protein synthesis but does not affect nucleic acid synthesis. It binds to the 23S rRNA of the bacterial 50S ribosomal subunit, which includes the activities such as catalyzation of  peptide bond formation, prevention of premature polypeptide hydrolysis, provision of a binding site for the G-protein factors, assistance of protein folding after synthesis. blocking of protein synthesis by inhibiting the transpeptidation or translocation step of protein synthesis and by inhibiting the assembly of the 50S ribosomal subunit. Azithromycin was the target of an enantioselective synthesis, which is a chemical reaction where one or more new elements of chirality,a molecule that has a non-superposable mirror image, are formed in a substrate molecule and which produces the stereoisomeric products in unequal amounts are formed in a substrate molecule and produces the stereoisomeric products in unequal amounts. Also, all the stereogenic quaternary carbon centers were enhanced by the desymmetrization of 2-substituted glycerols using a chiral imine/CuCl catalyst, otherwise known as copper (I) chloride.

   Screen Shot 2014-04-23 at 8.38.47 AM.png

     Synthesis of antibiotics such as erythromycin and azithromycin shows how the chemical structure and formula can be modified in order to change its function and its effect on the body accordingly. Although erythromycin was created first, scientists and doctors were able to enhance its molecular formula in order to enhance the process and activity in which it deals with an infected area. Also, these synthetic drugs offset and affect series of reactions such as hydrolysis, which can either interfere or not affect other processes. Overall, the synthesis of such antibiotics require much difficulty due to the fact that many factors such as the complexity of the compound or different incorporated ingredients that change the orientation of each function and process.

The Antidepressant

Kinetic and mechanistic evaluation of antidepressant medication

A Brief Overview 

Neurons in the human brain transfer information through an electrochemical process that culminates in the brain interpreting the transmitted data.  Between normal human neurons there exists a synapse through which envoy neurochemicals cross. The presynaptic, or initial neuron taking part in communication, produces chemical courier neurotransmitters. After being transported to the neuron’s external surface, these neurotransmitters are sent into the synapse and find a receptor area on the secondary, or postsynaptic, neuron. By doing so, the chemical messengers have now relayed their message, which will catalyze processes in the secondary neuron, among which include further construction of new neurotransmitters. When a surplus amount of neurotransmitters are put into the synapse, the initial neuron has the ability to reclaim this excess. Portions that go through reuptake are destroyed in the neuron and used as crude product for future undertakings. At the origin of antidepressants were the monoamine oxidase inhibitors, or MAOIs, which stemmed from the tuberculosis drug iproniazid. This medication became a treatment for depression, having the ability to obstruct the elimination of recycled neurotransmitters. A heightened sense of positive mood and energy in those who were medicated came from blockage of the enzyme that disintegrated norepinephrine, serotonin and dopamine.

Tricyclic antidepressants

In an analogous manner, tricyclic antidepressants hinder reprocessing of norepinephrine and serotonin, both expanding the success of the message in traveling to the second neuron and permitting neurotransmitter excess to remain in the synapses. Tricyclic antidepressants (TCAs) categorize a set of antidepressant medications that have homologous chemical structures and efficacy. Due to depression’s perceived roots in the disproportion of neurotransmitter levels, tricyclic antidepressants promote levels of norepinephrine and serotonin while impeding the function of acetylcholine. Anafranil, Elavil, Norpramin, Pamelor, Sinequan, and Tofranil are all
commercial names of tricyclic anImipraminetidepressanst that are currently on the market, representing a now aged class of treatments combating depression. Muscarinic, histaminergic and α1-adrenergic receptors are antagonized in the action of classical TCA drugs, leading to anticholinergic (rendering inactive the neurotransmitter acetylcholine), sedative, and cardiovascular effects. In vitro, fluoxetine unites with the aforesaid receptors in the brain tissue with less efficacy than TCA drugs. As identifiable through their names, these TCAs have a three-ring chemical structure. For example,

Mechanism of Action in Tricyclic Antidepressantsin imipramine (tofranil), the crucial portions of antidepressant activity include the ring system, sidechain extent, and location of the substituent groups. In this way, the most vigorously occupied compounds are the secondary methylamines (organic compound) and a small amount of primary amines (functional group with a atom of nitrogen coupled with a lone pair). In terms of sedative action apart from imipramine’s antidepressant properties, the tertiary amines deal with this mechanism while not taking part in the prime purpose.

Mechanism of Action in Tricyclic Antidepressants

Selective Serotonin Reuptake Inhibitors

As opposed to TCAs, there exists a class of compounds termed selective serotonin reuptake inhibitors(SSRIs), now the most prescribed antidepressant medications in numerous countries. In the creation of the SSRIs the method of rational drug design was used for the first time among the psychotropic drug class (psychoactive drugs traverse the blood-brain barrier, affecting the central nervous system of the human body and altering brain activity), where a definitive biological mark was identified and made an objective to a treatment.  An example of a prominent selective serotonin reuptake inhibitor, working by delaying the reuptake of serotonin into the human platelets so the serotonin that is released remains for a longer period of time, is Prozac. The chemical formula of Prozac is C17H18F3NO (systematic name: N-Methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-1-propanamine. Prozac is the trade name for Fluoxetine.  The fluoxetine molecule contains a variety of functional groups. There are two phenyl groups (benzene rings), an ether, and an amine.  Prozac is also a chiral molecule, meaning that they display a symmetry to their mirror image, often causeProzacd by the location of an asymmetric carbon atom in the general structure. This is a feature to be noted due to its usages in inorganic, organic, physical, and biological chemistry. It is metabolized by CYP2D6 by the liver, characterized by its slow rate and a long half-life in the confines of the system. Slow aggregation leads to delay in the manifestation of meaningful effect. It is also an agonist for 5HT2C receptors, linking back to the first blog post on beta-agonists.

Agonists, as aforementioned in the previous post, are chemical compounds that bind to receptor area and initiate the receptor to a form of action. Contrary to an antagonist which thwarts an action, the agonist strength is strongly linked to its half maximal effective concentration, otherwise known as EC50. This is the concentration of the substance that causes an intermediate effect between a minimum and maximal point after a definite period of time. In research regimens that follow a dose response, this represents the 50% efficacy point, and correlates to the IC50 that ascertains a substance’s inhibition. The slowing of the increasing ligand concentration response is an inflection point at which the EC50 occurs. This is pertinent due to the fact that the ligand is the functional group molecule or ion that connects to a center metal atom in the creation of a coordination complex, where there is a transfer of electron pairs from the ligand to the metal element. The bonds created in the process can be characterized as ranging from the covalent strength to ionic bonds, while the bond order is conventionally from one 1-3. In most circumstances, these ligands are also Lewis bases, and in Gilbert N. Lewis’ definition, are characterized as electron-pair acceptors that have the capacity to react with a Lewis base and result in the Lewis adduct. Furthermore, the ligand is what prescribes the reactivity of the central metal atom and redox. In conditions where the oxidation state is unclear, the ligand is non-innocent, present in heme proteins and with redox not focused on the ligand. (The innocent ligand does not change in oxidation state, for example in the the reduction of MnO4 to MnO42-. As you can see, the transformation occurs in the change in oxidation state of manganese from 7+ to 6+. The oxide ligand remains at an oxidation state of 2-, though a meticulous analysis would show that the ligand is changed in an alternate way by the redox).


3D animated view of Prozac Molecule

The Mechanism of Prozac


In this post we will discuss antibiotic resistance and how different ‘superbugs’ are being created because of continued use of antibiotics.

Antibiotic resistance is the ability of bacteria to resist the effects of an antibiotic. This usually occurs when bacteria change in some way that reduces or eliminates the effectiveness of drugs, chemicals, or other agents designed to cure infections. These bacteria survive and continue to multiply, causing more harm. This resistance can cause significant danger for people who have common infections that were once easily treatable with antibiotics. Every time a person takes antibiotics, sensitive bacteria are killed, but resistant germs may be left to grow and multiply.

Here is an interesting TED Talk by Dr. Karl Klose, which describes the ‘superbug’ and how different bacteria evolve into ‘antibiotic-resistant menaces’.

The big question is how bacteria become resistant to antibiotics. There are two answers to this question. One way that bacteria become resistant to antibiotics is by mutations in DNA. These mutations occur spontaneously and can have two different effects. A change in DNA of bacteria could lead to the prevention of bacterial protein synthesis. In our previous post we discussed how antibiotics target and attack these proteins. However, if the bacteria is active without the protein, there will be nothing for the antibiotics to attack. Mutations causing variations in the shape or size of the protein prevent antibiotics from being able to properly bind to the target protein. Another change in the DNA of bacteria could lead to the overproduction of protein enzymes. This overproduction could lead to various issues. Firstly, a particular dose of antibiotics would not be able to deactivate an overproduction of protein enzymes. Furthermore, some of the proteins produced may be alter the permeability of the cell membrane of cell wall of the bacteria. Aside from spontaneously occurring mutations in the DNA of bacteria, bacteria can become resistant to antibiotics as a result of gene borrowing. According to microbiologist Doctor John Turnidge,  “They’re the original life forms almost, so for thousands of millions of years they’ve had a chance to work out ways to survive and one of those is to borrow genes from other bacteria to survive.” Antibiotic resistance can result from DNA mutations or gene sharing among bacteria. The image below explains how the population of antibiotic resistant bacteria has increased tremendously. For more information regarding the process and causes of antibiotic resistance, check out this website

Since the advent of penicillin in the 1940s, antibiotic use has been steadily increasing. Antibiotics are used far more than necessary; they are used as a precautionary measure ‘just in case’ or as a comfort to patients who have viral or fungal infections. According to the CDC, 50 million of the 150 million prescriptions for antibiotics annually are unnecessary. Doctors would rather sign off on a prescription than spend the extra time trying to educate patients on the strengths and weaknesses of antibiotics. In addition to that, increasing use of hand sanitizer and antibacterial cleaning agents also contributes to the development of superbugs. The excessive use of antibiotics has already started to have devastating effects. But why? In the body, antibiotics kill enough bacteria so that the body can finish the job. Shouldn’t more antibiotics just kill more bacteria? It would seem that we should always take antibiotics and heed the adage ‘better safe than sorry’, right? Wrong.

That type of thinking will only drive us towards the edge faster, and here’s why: As soon as researchers develop new antibiotics, there are always already bacteria with the capabilities to defeat them. These resistant bacteria survive the antibiotic agents to multiply and divide, passing on their antibiotic resistanceto their progeny. As a result, the same antibiotics become less effective with time and it becomes harder and harder to develop antibiotics for these so called ‘superbugs’. The most famous strain of bacteria that has risen due to increasing antibiotic use is methicillin-resistant Staphylococcus aureus, or MRSA.

The CDC is currently working to reduce the amount of antibiotics used, because unchecked, it could become a serious public health issue. Already, 2 million people in the US are infected annually by antibiotic resistant bacteria. Should antibiotics continue to be prescribed at such an alarming rate, we could face a post-antibiotic age, in which antibiotics have been rendered useless.

The Mysterious Shortage

If you’ve recently watched NBC Nightly News you may have heard of the impending helium shortage (the topic for our next post), but there is another shortage, perhaps as equally impacting as the helium shortage, that most people have not heard about. That’s because this shortage happens all the time. It is the drug shortage. Where did all the drugs go? They didn’t go to Colorado as some might suspect with the recent legalization of marijuana. These are prescription, FDA-approved drugs that are on shortage, not recreational drugs normally run by drug cartels. But what’s even more interesting is that the drug shortage isn’t a normal shortage. As explained before, these shortages occur all the time, but only to a select number of prescription drugs, and these shortages are much more temporary compared to the helium or Plutonium-238 shortage. Nevertheless, that doesn’t mitigate the impact of this constant shortage. So why is there a drug shortage? As the FDA explains, these drug shortages are due to a number of reasons, most commonly manufacturing or quality problems. As we explore both of these factors, and examples of current drug shortages, you will see how both issues can affect a large population, not tomorrow or in 2025, but now.

To understand a little more about the underpinnings of this unknown shortage, you must first understand how competitive and difficult it is to bring a drug to market. The process often takes a couple of years and a couple billion dollars. The tests for safety are rigorous and lengthy and the paperwork fills dictionaries. It is no wonder why drugs are so expensive and why drug companies will do everything they can to make more money…

So what goes into this testing process regulated by the seemingly “devilish” FDA? Once a company has created a new drug, it can begin the FDA’s Drug Review Process. To start, there are preclinical animal testings. This phase is simply to identify whether the drug is lethal at its prescribed dosage. If it kills a mouse, you certainly do not want to give it to a human. Results must be shown to and reviewed by the FDA before human trials can begin. This transition to human clinical trials is marked by an Investigational New Drug (IND) Application. The first human trial is called Phase 1 where 20-80 healthy patients are given the drug simply to gauge the drug’s safety in humans and discern how the drug is metabolized and excreted. If it is determined that there isn’t an unreasonable toxicity Phase 2 trials begin. Phase 2 tests the effectiveness of the drug compared to placebos in treating a certain ailment. Typically a few dozen to 300 patients partake in Phase 2. If the drug is determined as effective, Phase 3 begins. Phase 3 are mass testings, often with a few thousand participants. This phase tests the drug’s interaction with other drugs and once again the drug is reviewed for its safety and effectiveness. The results are reviewed and finally all phases, trials and results are reviewed in a New Drug Application (NDA). Not so bad? The entire process can take up to 12 years, and drugs have a 1 in 5000 chance of making it through the process.

What does this have to do with the problem at hand? Well, besides bankrupting any small company, the FDA regulates drugs on a much lower frequency once a drug is brought to market with the thought that these drugs are safe. However, this means that your safety is not guaranteed. Often times a demand for a drug will increase, while just as frequently a manufacturing company may close down thereby decreasing supply. This is how a manufacturing and consumerism problem can lead to a shortage. But remember, the drug company just paid, on average, 4 billion dollars to bring that drug to market, there is no way a small manufacturing problem is going to stop the drug company from selling their drug. So what might a drug company do? Come up with a cheaper, more efficiently manufactured formula for the drug and begin manufacturing that. What’s to stop them? The FDA is not due for a visit in another year – hopefully the new formula won’t hurt anyone. And that’s how quality problems arise. A simple change in the formula harms a select, but noticeable, clientele and they report the problem to the FDA. That’s when the FDA’s visit to the drug company is unexpected and a lot sooner than their annual or biannual visit. The FDA will halt all production of the drug, and begin running testings and reviews of the drug once more. So as you can see the two factors – manufacturing and quality – are interlinked and sometimes a drug company will simply pick the lesser of two evils. This makes for a very harmful shortage not only when the formula of the drug is changed, but also in either scenario when production of the drug is slowed or halted and the patientneeding the drug cannot get it.

So what are some current drug shortages, what do the drugs do and who do the shortages affect? An interesting one with many applications is Dexamethasone Sodium Phosphate Injections.

Dexamethasone Sodium Phosphate InjectionsGlucocorticoids[1]

Dexamethasone is a potent glucocorticoid (the term glucocorticoid is interchangeable with corticoid or corticosteroid) and the injection of Dexamethasone Sodium Phosphate is used to treat allergic reactions, arthritis, blood diseases, breathing problems, eye diseases, intestinal disorders and more. It can also be used to diagnose an adrenal gland disorder (Cushing’s disease) since the adrenal gland is responsible for secreting corticoids. Dexamethasone and other corticoids are anti-inflammatory and is the reason why they can be used to treat ailments like allergic reactions, arthritis or skin disorders (such as bug bites). This is because dexamethasone binds to the glucocorticoid receptor – since they are complementary in structural shape [1] – which is responsible for suppressing the immune system (and heightening awareness). During times of stress, the adrenal gland releases corticoids, which bind to the glucocorticoid receptor. The body suppresses all non-essential functions (i.e. the immune system) and heightens all functions beneficial to survival (i.e. attention). This natural phenomena is used to stop inflammation, a natural immune response. It is also the reason why withdrawing from dexamethasone or any other corticoids can cause weakness and tiredness.

Because of its versatility, the dexamethasone sodium phosphate injection shortage affects many people who need a wide variety of treatments. There are 4 manufacturers of the dexamethasone sodium phosphate injection, but over half of the concentrations of the injection are unavailable from all suppliers. One concentration from a certain supplier may not recover until April, 2014 because of increased demand. Most of these backorders or unavailability began in January of 2013.

Calcium chloride injections are also in shortage, and while they aren’t as widely applicable as Dexamethasone Sodium Phosphate injections, their absence is just as life-threatening. Calcium chloride (CaCl2) is normally a crystal structure as depicted in the below two pictures.

CaCl2Calcium Chloride Solid

Its crystal structure forms a rather unique cubic unit cell with a total of 2 Calcium atoms and 4 Chloride atoms – appropriately so since there should be twice as many Chloride atoms as there are Calcium atoms. 8 Calcium atoms reside in each corner of the unit cell, and since each contribute 1/8 to the unit cell, that is a total of 1 Calcium atom. Another Calcium atom resides in the center of the unit cell. What makes this unit cell so interesting though is the placement of the Chloride atoms make this cubic unit cell neither a face-centered unit cell nor a body-centered unit cell. 2 Chloride atoms reside completely within the unit cell, while 4 Chloride atoms reside on the faces, each contributing 1/2 to the unit cell which accounts for the 4 total Chloride atoms that are within the cubic unit cell.

As a solid, Calcium chloride is commonly used as brine for refrigeration plants, salt on roads to prevent ice, and desiccation, or the removal of water by chemical means. However as a liquid, the Calcium chloride injection is used for immediate treatment of hypocalcemic tetany, uncontrollable muscle contractions and spasms due to a lack of Calcium in the body, treatment for insect bites, aid for depression due to an overdose of Magnesium sulfate (which happens to be another drug currently on shortage – not because of an increase in overdoses, and the two shortages are not related) and to improve weak or ineffective myocardial heart contractions when epinephrine (in injection form is also on shortage. Again, the two shortages are not related) has failed to due so (usually after open heart surgery). Calcium chloride injections are vital to both hypocalcemic tetany, since the cause of the illness is a lack of calcium, and recoveries from open heart surgeries. Again, while both diseases are rare and far less common than the diseases dexamethasone sodium phosphate injections treat, this shortage can have detrimental effects. The shortage began in December of 2012, and still has yet to recover since half the suppliers have either discontinued manufacturing calcium chloride injections, or were having trouble manufacturing enough for the increased demand.

 The final shortage worth touching upon is the copper injection shortage which is often delivered as cupric sulfate (Cu(II)SO4).


This interesting cubic unit cell is even more complex than that of calcium chloride. Again it is neither a simple cubic, face-centered cubic nor body-centered cubic unit cell but rather a combination of them all “plus more”. The copper ions reside in the corners of the unit cell, the edge of the unit cell, the face of the unit cell and in the center of the unit cell. A copper ion resides on each corner and since each contribute one eighth of an ion (8*1/8) that amounts to 1 ion. Next there are 4 edge cells which contribute one fourth of an ion (4*1/4) which totals another ion. Then there are 2 face centered ions which each contribute half an ion (2*1/2) which is another ion. Finally there resides one copper ion in the center of the unit cell. In total there are 4 copper ions. Further evaluation of the unit cell concludes in the fact that there are 4 sulfur ions and 16 oxygen ions within the unit cell, or otherwise 4 sulfate (SO4-2) ions. This makes sense since the ratio of copper to sulfur to oxygen ions is 1:1:4 and the ratio of copper ions to sulfate ions is 1:1.

Copper injections are used in IV therapies (Intravenous therapies) as a part of total parenteral nutrition (TPN). Copper is necessary, in small quantities, in a human diet and when a patient cannot eat, it is required that they receive their nutrients in another manner; IV therapies. IV therapies are used often in hospitals so this shortage may have a significant impact on hospital patients and is the reason why this may be the most urgent shortage mentioned in this blog. The shortage is not only life threatening to those who need it, but it also affects a large population. The shortage began in April of January and the sole manufacturer has halted production of the injection. The only signs of hope are Cupric Chloride injections, another form of copper injections which are expected to recover from their own shortage sometime this quarter.

Hopefully, as you can begin to see, the fairly unknown drug shortage, is a very serious problem. Luckily most shortages are due to manufacturing delays and not quality problems (perhaps drug companies are not as greedy as the public might believe), but the shortages which can last months, are still detrimental to those who need the drugs. As the problem continues unnoticed by the general public, the best we can hope for is a revamping of manufacturing of dozens of drugs on shortage to satiate the ever-increasing demand for drugs.