Friday, July 28, 2017

New Imaging Technique in Surface Chemistry

As being a surface chemist, I keep on tracking the signs of progress made so far in the Surface Chemistry field. Recently, I found good news about the imaging tool in surface chemistry. Here is the story:
Researchers at Ecole Polytechnique Fédérale de Lausanne (EPFL) Laboratory for Fundamental BioPhotonics (LBP) have developed a microscope that can track, in real time, 3D spatial changes in the molecular structure and chemistry of confined systems, such as curved surfaces and pores to understand the geological, catalytic, biological and chemical processes which are driven by surface chemical heterogeneities, electrostatic fields and flow. They predict that this may enable the further development of new materials and microtechnology.
“An optical imaging tool to visualize surface chemistry in real time has been developed. This system basically images the interfacial chemistry in the microscopically confined geometry of a simple glass micro-capillary. The glass is covered with hydroxyl (-OH) groups that can lose a proton, a much-studied chemical reaction that is important in geology, chemistry, and technology. A 100-micron long capillary displayed a remarkable spread in surface OH bond dissociation constant of a factor of a billion.”
The developed microscope was used to image the surface chemical structure of the inside of a glass microcapillary. Surface potential maps were designed from the millisecond images, and the chemical reaction constant of each 188nm-wide pixel was evaluated. Amazingly, this very simple system which is used in many devices displayed a stunning spread in surface heterogeneity. The researchers' findings have been published in Science. It is believed that this method will be a plus point in understanding fundamental (electro)chemical, geological and catalytic processes and for building new devices.
Second-harmonic imaging
Imaging of surface potential and chemical process at the surface.
Image: taken from Google (28th July, 2017)
Sylvie Roke, director of the Julia Jacobi Chair of Photomedicine at EPFL, has developed a unique set of optical tools to study water and aqueous interfaces on the nanoscale. She uses second-harmonic and sum-frequency generation, which are optical processes in which two photons of a certain color are converted into a new color. "The second-harmonic process involves 1000 nm femtosecond photons i.e., 0.00000000000001-second bursts of light -- being converted into 500 nm photons, and this occurs only at interfaces," says Roke. "It is therefore ideal for interfacial microscopy. Unfortunately, the process is very inefficient. But by using a number of optical tricks, such as wide field imaging and light shaping, we were able to enhance both the imaging throughput and the resolution, bringing the time to record an image down from minutes to 250 milliseconds."
Surprising surface chemistry
The researchers then imaged the deprotonation reaction of the inner silica capillary/water interface in real time. Silica is one of the most abundant minerals on earth, and its interaction with water shapes our climate and environment. Although many researchers have characterized the properties of the silica/water interface, there is no consensus on its chemical reactivity. Roke continues: "Our data shows why there is a remarkable spread in surface reactivity, even on a very small portion of a capillary. Our data will help in the development of theoretical models that are more effective at capturing this surprising complexity. In addition, our imaging method can be used for a wide variety of processes, such as for analyzing the real-time functioning of a fuel cell, or for seeing which structural facet of a mineral is most chemically active. We could also gain more insight into nanochannels and both artificial and natural pores.
 1. Carlos Macias-Romero, Igor Nahalka, Halil I. Okur, Sylvie Roke. Optical imaging of surface chemistry and dynamics in confinementScience, July 2017 DOI: 10.1126/science.aal4346
2. Science Daily, July 28, 2017 Issue (

Friday, June 16, 2017

Pregnant Women and Coffee

“Coffee, for many of us, is a daily fix. But few would relate to it as being a life changer” – this is what BBC (27th Feb, 2013 issue) writes by narrating a story of Nepali farmer whose life was changed by farming coffee instead of regular maize and paddy cultivation. Nepalese coffee is different from other countries. People mainly produce Arabica type of coffee which is organic. But, what about intake of coffee by Nepalese women? Frankly, in Nepal tea is preferred than coffee. Most of the people in the rural area take milk-added-tea which is considered more harmful than black tea. Let’s know something about caffeine, a key component in coffee and its effect on the pregnant women.

Caffeine is a natural component of coffee, tea, and cocoa products. It is added to many soft drinks and to certain prescription and over-the-counter medications. Caffeine's pharmacologic effects include central nervous system stimulation, bronchodilation, and higher blood pressure, most likely through antagonism of adenosine receptors in the brain, heart, lungs, and blood vessels. Based on a recent survey by the U.S. Department of Agriculture, coffee, soft drinks, and tea (in that order) are the major sources of caffeine among adults. Average caffeine intake is estimated to be 164 mg per day among women 18–34 years and 125 mg per day among pregnant women. In a prospective cohort study conducted in Connecticut during 1988–1992, caffeine consumption during the first month of pregnancy was reported by 60% of study participants, with 16% consuming 150 mg or more of caffeine per day.

Caffeine is teratogenic in animal studies when administered at high concentrations. There is no evidence to support a teratogenic effect of caffeine in humans. Current epidemiologic evidence is not adequate to assess the possibility of a small change in risk of congenital anomalies resulting from maternal caffeine consumption.

Picture from Google on 16th June 2017 
Marilyn Brown has published a review paper in epidemiology journal by evaluating methodological aspects of epidemiologic studies of maternal caffeine exposure and risk of congenital anomalies1. He has reported that there is no evidence that caffeine intake causes a large increase in the risk of various types of congenital anomalies, but there is greater uncertainty about small elevations in risk. Given the relatively high prevalence of maternal caffeine exposure, even a small increase in the risk of congenital anomalies would have an important effect on public health. 

Large study populations and improved exposure assessment methods would be necessary to rule out small risks for specific categories of congenital anomalies after maternal exposure to caffeine.
In the United States, some 60 percent of women continue to drink caffeinated coffee during their first month of pregnancy.  About 16 percent of pregnant mothers consume 150 mg of caffeine or more per day. But the question is, Is this harmful to your unborn baby? Three things to know.  One, caffeine can freely cross the placenta.  Two, 90 percent of a mother’s caffeine level reaches the developing fetus.  Three, the half-life of caffeine is much longer in the fetus than in the adult2.
Some studies have shown a correlation between prenatal caffeine consumption and decreased birth weight.  But are there longer-term consequences? Researchers in Florida studied mice that had were exposed to physiologically relevant doses of caffeine in utero.  They found that caffeine significantly altered the expression of genes in embryonic hearts.  Pathways related to cardiovascular development and diseases were significantly affected by caffeine. The researchers stress that “the long-term effects of caffeine on human cardiac function are unclear.”  They recommend further studies “to evaluate the safety of caffeine exposure during human pregnancy.”

1.         Browne, M. L., Maternal exposure to caffeine and risk of congenital anomalies: a systematic review. Epidemiology 2006, 17 (3), 324-331.
2.         Fang, X.; Mei, W.; Barbazuk, W. B.; Rivkees, S. A.; Wendler, C. C., Caffeine exposure alters cardiac gene expression in embryonic cardiomyocytes. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 2014.

Friday, November 18, 2016

Viagra (Sildenafil) And Its Chemistry

     Erectile dysfunction is a common problem faced by elderly men. According to a report, about 60% of men older than 60 and 70% of those in their 70s have trouble getting or maintaining erections, often because of diabetes, cardiovascular disease or prostate cancer treatment. Not all of them want treatment, of course. A large proportion of older men have lost sexual interest, don’t have a partner or have other illnesses that preclude sexual activity. Paula Span writes in The New York Times (July 31, 2015 issue) on a heading “Sex Never Dies, but a Medicare Option for Older Men Does”. Yes, it does. She also writes that Medicare (Government medical insurance in USA) stopped covering erection pumps from July 1, 2015 an indication, some experts say, that the sexual health of older adults is not taken seriously. These erection pump treatment option naturally pulls blood into the erectile tissues to help men maintain an erection without medication or invasive procedures. That is another aspect to be discussed. Here, I want to discuss about the medication suggested by experts for erectile dysfunction and its chemistry.
    Viagra (sildenafil) is a suggested medicine for the erectile dysfunction for men (also women) that relaxes muscles found in the walls of blood vessels and increases blood flow to particular areas of the body. It has been since long to treat erectile dysfunction (impotence) in men. Another brand of sildenafil is Revatio, which is used to treat pulmonary arterial hypertension and improve exercise capacity in men and women. The chemical formula of Viagra is C22H30N6O4S and its IUPAC name is 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d] pyrimidin-5-yl)-4-ethoxyphenyl] sulfonyl]-4-methylpiperazine citrate.
Pfizer scientists Andrew Bell, David Brown, and Nicholas Terrett originally discovered sildenafil as a treatment for various cardiovascular disorders. Since becoming available in 1998, sildenafil has been a common treatment for erectile dysfunction; its primary competitors are tadalafil (Cialis) and vardenafil (Levitra). Beside the treatment of erectile dysfunction, sildenafil is also used in pulmonary hypertension. While sildenafil improves some markers of disease in people with pulmonary arterial hypertension, it does not appear to affect the risk of death or serious side effects as of now. Furthermore, it has also been used as antidepressant-associated sexual dysfunction. Tentative evidence suggests that sildenafil may help men who experience antidepressant-induced erectile dysfunction. In addition, the altitude sickness problem has been solved surprisingly by it. Sildenafil appears to improve some risk factors for high-altitude pulmonary edema but it is unclear whether or not it affects the rate of the condition itself.
    There are few side effects due to the administration of this drug in human body. Common side effects include headaches and heartburn, as well as flushed skin. Caution is advised in those who have cardiovascular disease. Rare but serious side effects include prolonged erections, which can lead to damage to the penis, and sudden-onset hearing loss. Sildenafil should not be taken by people who take nitrates such as nitroglycerin (GTN), as this may result in a severe and potentially fatal drop in blood pressure. Let’s know how this drug acts on the targeted area.
Mode of Action
Schematic illustration adopted from Peter Volsky
  Robert F. Furchgott, Ferid Murad, and Louis Ignarro won the Nobel Prize in Physiology or Medicine in 1998 for their independent study of the metabolic pathway of nitric oxide in smooth muscle vasodilation. In their study, they found that Sildenafil (Viagra) protects cyclic guanosine monophosphate (cGMP) from degradation by cGMP-specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum. A corpus cavernosum is one of a pair of sponge-like regions of erectile tissue, which contain most of the blood in the penis during an erection. Nitric oxide (NO) in the corpus cavernosum of the penis binds to guanylate cyclase receptors, which results in increased levels of cGMP, leading to smooth muscle relaxation (vasodilation) of the intimal cushions of the helicine arteries. The helicine arteries of penis are arteries in the penis which are involved in the process of erection. This smooth muscle relaxation leads to vasodilation and increased inflow of blood into the spongy tissue of the penis, causing an erection. 
   Sildenafil is best regarded as a potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum. Various researches have shown that the molecular structure of sildenafil is similar to that of cGMP and acts as a competitive binding agent of PDE5 in the corpus cavernosum, resulting in more cGMP and better erections. Without sexual stimulation, and therefore lack of activation of the NO/cGMP system, sildenafil should not cause an erection. Other drugs that operate by the same mechanism include tadalafil (Cialis) and vardenafil (Levitra).
      After its desired action, Sildenafil is broken down in the liver by hepatic metabolism using cytochrome p450 enzymes, mainly CYP450 3A4(major route), but also by CYP2C9 (minor route) hepatic isoenzymes. The major product of metabolisation by these enzymes is N-desmethylated sildenafil, which is metabolised further. This metabolite also has an affinity for the PDE receptors, about 40% of that of sildenafil. Thus, the metabolite is responsible for about 20% of sildenafil's action. Sildenafil is excreted as metabolites predominantly in the feces (about 80% of administered oral dose) and to a lesser extent in the urine (around 13% of the administered oral dose). If taken with a high-fat meal, absorption is reduced; the time taken to reach the maximum plasma concentration increases by around one hour, and the maximum concentration itself is decreased by nearly one-third.