Key Concepts for Medicinal Chemists

Molecular recognition in biological systems occurs by the complementary non-covalent bonding between a receptor binding site and a ligand (e.g., drug molecule). The attached concepts, numbers, and formulae assist medicinal chemists in structural modification related to the drug-receptor binding.

Picture of Olympicene

Back in 2009, at the IBM Research lab scientists imaged, for the first time, the chemical structure of an individual molecule (pentacene) with unprecedented resolution, using technique they developed called noncontact atomic force microscopy. The same IBM team, has once again come up with an interesting image. This time they have imaged a new organic molecule, Olympicene.

Olympicene, gets its name because its five linked rings resemble the Olympic symbol. The compound is a powder, that is very sensitive to light. In fact, even with brief exposure it changes color. It is only 1.2 nanometers wide, or 100,000 times thinner than a human hair. This AFM technique could become a real structure-determination tool for organic chemist.

PhD student fellowships

The International Max Planck Research School (IMPRS) "The Exploration of Ecological Interactions with Molecular and Chemical Techniques" in Jena, Germany, invites applications for 6 Ph.D. fellowships.

The application deadline is June 29, 2012.

For detailed information about the IMPRS, Projects offered, and application requirements, @http://imprs.ice.mpg.de/.

Molecule vending machine

Nano-catalysis is a fast-growing field of chemistry, which involves the use of nanomaterials as catalysts for a variety of selective organic transformations. Nano-catalysis can be considered as a bridge between homogeneous and heterogeneous catalysis. Because of the high surface area of nanomaterials, the contact between reactants and catalyst increases dramatically, and they can operate in the same manner as homogeneous catalysts (homogeneous catalysis); at the same time, due to their insolubility in the reaction solvent, they can be separated out easily from the reaction mixture (heterogeneous). Only the molecules of certain sizes and chemical properties are selected and guided to the reaction centers, where they are efficiently transformed into the desired products.

Solid supports have the potential to house more than one metal and, hence, catalyze multiple types of bond constructions. Such “multifunctional” catalysts attained much attention due to several advantages over mono metal catalysts. The high selectivity of the nanocatalyst may help reduce the energy consumption required for product separation and waste disposal processes in chemical industries.

Totally drug-resistant TB

One of the biggest problems in Tuberculosis (TB) therapy nowadays is that patients have to take antibiotics for up to 9 months. As many patients feel better before this time, they prematurely stop their treatment, leaving pools of the most drug-resistant M. tuberculosis in their lungs. This contributes to the emergence of complete drug resistance in future patients.

In the past few years, strains of drug-resistant Mtb have become prevalent. In fact, resistance is so widespread that it is now being classified as multi-drug resistant (MDR-TB) and extreme-drug resistant (XDR-TB). Two of the world’s most populous countries, India and China, account for more than 50% of the world’s MDR-TB cases.

Recent reports have also confirmed a new Mtb strain that is completely untreatable and has been designated as Totally drug resistance TB (TDR-TB). Indeed, strains of Mtb have even evolved resistance to all major available anti-TB drugs. India (2012) is the third country in which a total drug-resistant form of TB has emerged, following cases documented in Italy in 2007 and Iran in 2009. There is a need for a more readily available treatment that is effective against both sensitive and drug-resistant strains of M. tuberculosis is evident.

Nano reactions

Recently, nanoporous materials have emerged as important and efficient heterogeneous catalysts for organic transformations due to their excellent textural characteristics, including high surface area, large pore volume, uniform pore size distribution, and simplicity in workup recyclability. The pore diameters are chosen to control the access of molecules to the catalytic reaction sites located inside the porous cavities. Only the molecules of specific sizes and chemical properties are selected and guided to the reaction centers, where they are efficiently transformed to the desired products.

What is a PhD worth?

Here is another article  in nature that makes some good points about the worth of a Ph.D.

"The number of science doctorates earned each year grew by nearly 40% between 1998 and 2008, to some 34,000, in countries that are members of the Organisation for Economic Co-operation and Development (OECD). The growth shows no sign of slowing: most countries are building up their higher-education systems because they see educated workers as a key to economic growth. But in much of the world, science Ph.D. graduates may never get a chance to take full advantage of their qualifications"

Ph.D. program used to be for science-loving driven people, and the world wants more innovation from academic science to solve global problems.

Mycobacteria and the great wall

The mycobacterial cell wall is unique, thick waxy, and hydrophobic, ensuring its survival inside human macrophages by resisting oxidative damages. The waxy, highly impermeable nature of the wall provides the required defense mechanism against antibiotic agents and the host organisms. A key component of the cell wall is mycolic acids. Mycolic acid accounts for up to 60% of the organisms' dry weight, which means that most percentage of mycobacteria is a cell wall. A thorough understanding of the influence of polarity on drug penetration into a highly impermeable mycobacterial cell wall will improve permeability.

The permeation ability of a lipophilic molecule is inversely related to the cell wall's fluidity, which decreases as the length of fatty acids in the mycolic acids layer increases. The permeability barrier presented by this cell envelope is also thought to be why many common antibiotics are ineffective against mycobacteria. Lipophilic drugs, such as fluoroquinolones or rifamycins, pass more quickly through the lipid-rich cell wall and thus are more active.

Depending on the library screens towards compounds with a particular physicochemical parameter could be detrimental and decrease the diversity in finding new anti-TB drugs.