Medicinal and Environmental Chemistry: Experimental Advances and Simulations (Part II)

Air pollution is a major environmental health threat due to the increasing rate of morbidity and mortality associated with it. The World Health Organization (WHO) classified particle pollution (PM10 and PM2.5), tropospheric ozone (O3), carbon monoxide (CO), sulfur oxides (SOx), nitrogen oxides (NOx), and lead as six major air pollutants. Particulate matter (PM) can penetrate the respiratory system, causing respiratory and cardiovascular diseases. Stratospheric ozone plays a protective role against ultraviolet irradiation, but ozone is harmful when present in the troposphere, affecting the respiratory and cardiovascular systems. Nitrogen oxide, sulfur dioxide, carbon monoxide, and lead are harmful to humans causing respiratory problems, such as Chronic Obstructive Pulmonary Disease, asthma, bronchiolitis, lung cancer, and cardiovascular events. The only possible way to cope with this problem is through public awareness coupled with a multidisciplinary approach by scientific experts. The Government of India made the Pollution Prevention and Control Act, 1981, for the prevention of air pollution. Prime Minister Narendra Modi launched the Ujjwala scheme on 1st May 2016, from the Balia district in Uttar Pradesh. The scheme is aimed at replacing unclean cooking fuels. The Ministry of Environment, Forest, and Climate change has started the National Environment Health Profile (NHEP) study, involving 20 cities, to assess health effects associated with environmental exposure. The National Clean Air Programme (NCAP) has also been launched for pan-India implementation to tackle the increasing air pollution problem in the country (102 cities); the tentative national level target is 20%–30% reduction of particulate concentration by 2024.

The rising levels of smog, blanketing northern parts of India during October-January in recent years, have pushed pollution levels to an extremely hazardous point. The pollutants and the particulate matter (PM) generated by various activities have a very harmful effect on human health. This has resulted in an increase in human diseases, especially of the respiratory and cardiovascular organ systems. Combustion results in the formation of redox-active metals and aromatic hydrocarbons, which stay in the environment long after the activity has ceased. These moieties form air-stable, environmentally persistent free radicals on entrained particles that harm the pulmonary and cardiovascular systems. The protective mechanisms of the bronchopulmonary tract are unable to stop the ultra-fine air pollutants from invading the body. The various by-products of smog enter the human body via several different routes, finally reaching the liver for detoxification by Cytochrome P450 (also known as CYPs). Negative health effects of air pollutants have been shown on the cardiovascular system resulting in multiple respiratory diseases, including respiratory infections, asthma, chronic obstructive pulmonary disease (COPD), lung cancer, even in combination with stroke and heart diseases. The CYPs are endoplasmic reticulum resident enzyme systems that are involved in the metabolism of xenobiotics as well as drugs. The free radicals have a deleterious effect on these enzymes and have been found to inhibit six forms of P450 in rat liver microsomes. These free radicals are thought to inhibit CYP2B4-mediated substrate metabolism by physically disrupting the CPR•P450 complex.

Chronic obstructive lung diseases, including asthma and chronic obstructive pulmonary disease (COPD), are causing an extreme burden on societal health, affecting above 500 million people worldwide and affecting lung physiology at a multibiological level. The increasing burden of air pollution is a major contributing factor to the disease, other than smoking and living conditions. Over the years, several studies have been undertaken to understand lung function, airflow mechanisms, and impairment for better therapies and therapeutic interventions. Still, it is very unlikely to predict the morbidity and mortality associated with COPD due to limitations of early and timely prediction and progression which calls for personalized treatment interventions to avert exacerbation and refractory symptoms. This chapter presents an overview of the status of COPD worldwide with a special emphasis on Indian statistics, along with the drug and pharmacological advancement, and computational medicinal modelling, its applications, and limitations. Though experimental models may predict the prerequisites for the system medicine approach, they are unable to analyse the finer details, calling for more advanced molecular technologies. A computational model of system medicine mimics the functioning of a complex system and can predict future functioning as well. Working with large data sets, computational models may have greater benefits to minimize patient risk and assist in clinical decision-making.

Due to the overall industrial development and human activities, the demand for clean water in India is continuously on the rise. There already exists a danger to the geochemical environment owing to the indiscriminate withdrawal of groundwater, resulting in the release of Arsenic (As). In some localized areas this level of As has already exceeded the World Health Organization’s (WHO) permissible limits (10μg/L or 10ppb) for drinking water, leading to serious environmental and health consequences. Arsenic is predominantly present as inorganic species either as arsenate As (V) or arsenite As (III) in natural systems. In oxygen-rich environments where aerobic conditions persist, As (V) exists as mono-valent (H2AsO4)- or divalent (HASO4)2- anion, whereas, As (III) exists as an uncharged molecule (H3AsO3) and anionic (H2AsO3)- species in moderately reducing atmosphere where anoxic conditions persist. The concentration of arsenic above its permissible level results in skin sclerosis. Arsenic gets deposited in the tissues of the vital organs and may cause cancer of the liver, lung, and urinary bladder. This study is an attempt to (a) review the arsenic problem in Uttar Pradesh, (b) to bring out the health issues due to arsenic, and (c) find sustainable solutions to address the issue.

Environmental chemistry is the study of chemical processes occurring in the environment for understanding the diverse issues related to human health and resource conservation. These significant effects may be felt on a global scale, through the presence of water pollutants or toxic substances arising from chemical waste. The increasing world population, rapid industrialization, and human activities have resulted in higher water demand throughout the world. The fast spread of contamination problems worldwide and their effects on the natural resources of water led to the evolution of environmental chemistry. This evolution relies on the different membranes technology to facilitate the scientific investigations on the contamination extent and optimize remediation efforts. Polymeric ceramic composite membranes comprise a captivating field of membrane separation technology. Rapid development and innovation have been done in the modification of these membranes. These membranes have superiority in terms of high temperature and chemical resistance, higher chemical, and mechanical stability, and have higher longevity. All these outstanding features have made these membranes ideal for water treatment and desalination applications. This chapter is a review of the development, and the use of polymer composite membranes in treating wastewater. A brief description of synthesizing these membranes through different routes is given and is reviewed critically.

Anions are prevalent in nature and have important roles in many biological, medical, industrial, and environmental processes. These processes lead to the release of anions in the environment, which act as pollutants at higher concentrations. The proper management of these anions requires adequate detection techniques. Anion sensing, a branch of supramolecular chemistry, deals with chemosensors that are capable of selective recognition and detection of anions through optical or electrochemical response. Further, these compounds are also used for the construction of sensory devices and the extraction and separation of anions. Chemosensors are very useful for the detection of potentially toxic (e.g., fluoride, cyanide) and environmentally hazardous (e.g., phosphate, nitrate) anions as well as in medical diagnostics. Consequently, anion sensing has become one of the most active areas of supramolecular chemistry. The design and synthesis of anion-selective receptors and sensors are challenging, as compared to cation counterparts, due to their different sizes, shapes, high hydration energies, and pH-dependent properties. Three approaches have been used for the detection of anions by chemosensors viz. binding site-signalling subunit approach, displacement approach, and chemodosimeter approach. This chapter focuses on small molecular optical chemosensors and the mechanisms adopted for the detection of anions.

Antibiotics have been used as antimicrobial agents to fight a variety of infectious diseases, for the past more than 100 years. Apart from this, they are also extensively used in animal farming, agriculture, and aquaculture, all over the world. However, this frequent and large-scale overuse and incorrect use lead to the excessive dispersal of antibiotics in water and soil, resulting in their accumulation in the environment, which is known as antibiotic pollution. The removal of antibiotics from water and soil is complicated due to their non-biodegradable nature, and special techniques must be used for the same. This pollution has serious implications on both human health and the ecological balance. The major adverse effect is antibiotic resistance, wherein, microbes become less susceptible to treatment with antibiotics, posing problems for both the patient and the physician. This chapter describes the causes and consequences of antibiotic pollution, the challenges it presents, and the strategies to counter them.

The pharmaceutical residues and their metabolites present in soil and water have been considered as active pollutants, posing various health risks to humans. Major sources from where pharmaceutical compounds enter the environment are hospitals, pharmaceutical industries, domestic wastes, and improper disposal of medicines. Metabolism of drugs in humans is sometimes incomplete, resulting in their excretion in either the unchanged form or in the form of metabolites. However, biodegradation of pharmaceutical compounds and/or their metabolites in the environment is not easy; therefore, their repeated addition to the environment makes them even more persistent. The pharmaceuticals, based on their physicochemical properties, bind to soil particles or enter the aquatic system. The most adverse effect of increasing the concentration of pharmaceuticals in environmental matrices is the development of resistance in certain bacteria against antibiotics, which is a serious health concern. Steroidal hormones can alter the steroidogenesis of aquatic and terrestrial life and cause endocrine disruption, leading to cognitive and brain development problems. The concentration of pharmaceutical residues in the environment is very low; therefore, highly sensitive instruments for their quantification are required like liquid chromatography coupled with mass spectroscopy (LS-MS/MS) and gas chromatography with mass spectroscopy (GS-MS). The techniques allow the identification of various analytes with improved detection limits. The pharmaceutical residues are considered lethal pollutants, even if present in ng/kg or ng/l, and can cause potential harm upon exposure. This chapter aims to review various analytical approaches for pharmaceutical residue analysis and recent advancements made in analytical techniques.

Bioisosteres are chemical substituents, groups, atoms, or moieties that have similar physical and chemical properties, producing analogous biological effects but with greater impact and potency. Bioisostere replacement is an impactful concept in medicinal chemistry. Bioisostere replacement is used for attenuation of toxicity, enhancement of the activity of the lead compound, or alterations in pharmacokinetics and toxicity of the lead. This chapter deals with the degradation or minimization of ecotoxic waste through bioisostere replacement. The chapter details bioisosteric replacements for the degradation of eco-hazardous wastes in two ways, i.e., direct way and indirect way. The direct way involves bioisosteric changes in insecticides, which directly affects the environment, while the indirect way involves bioisosteric modifications in drug molecules to increase their bioavailability and half-life period so that maximum drug is consumed within the body, providing better efficacy against the disease and release of a minimum amount of waste into the environment. These modifications prove to be eco-friendly. Some important bioisosteric groups used for replacement are -fluoro, -deutero, -nitro, -t-butyl, and others. This chapter gives an insight into the plausible alterations with improved functional groups in bioisosterism to improve the eco-detrimental effects of compounds or drugs.

Two new metal-containing biosources i.e. Pyruspaschia fruits and Eurya acuminate leaves were used in the preparation of gold and silver nanoparticles.Pyruspashia has many medicinal uses as it is used in gastrointestinal disorders, fever, and headache, hysteria, and epilepsy. The fruits are sedative, febrifuge, and laxative. Eurya acuminate leaves are used as a treatment for cholera, diarrhoea, and other stomach diseases. The leaves are applied as a poultice on skin eruptions. These bio-sources are metal chelators used for binding natural dye to textile. These both metal-bearing plant parts were first time used to produce nanoparticles which further can be used therapeutically based on their size. This approach can add results to an environment-friendly medicinal agent. The nano-particles so generated were characterized by UV-Visible spectroscopy, FESEM (field emission scanning electron microscopy), TEM (transmission electron microscopy), and AFM (atomic force microscopy) techniques. The particles were found to be crystalline and both Au and Ag nanoparticles were pure and their mother liquor did not have significant sedimentation as impurities. FT-IR (Fourier transformed infrared spectroscopy) analysis authenticates the role of phytochemicals in this work. The synthesis of silver and gold nanoparticles using the above biological resources suggests an eco-friendly/green possibility, in comparison to many available methods based on chemical or physical techniques. Their application as therapeutic agents in various diseases and cancerous growth is of great prospect.

The current epidemic of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) has led to a major health crisis in 2020. SARS-CoV-2 has spike protein, polyproteins, nucleoproteins, and membrane proteins with RNA polymerase, 3-chymotrypsin-like protease, papain-like protease, helicase, glycoprotein, and accessory proteins. These are probable targets to be explored for the discovery of antiviral agents, still, to date, no definite treatment or vaccine has been discovered. Virtual screening with molecular docking has its advantage to speed up the drug development procedure in an accurate manner. In this chapter, novel computational strategies for drug discovery have been elaborated. Docking tools and drug filtering rules which may efficiently assist the drug development procedure and channelize the whole process in the right direction have also been discussed. A case study with 322 natural, semi-synthetic, and synthetic derivatives of citric acid (2-hydroxy-1,2- 3-propane tricarboxylic acid), in search of a potential lead molecule to combat the novel coronavirus SARS-CoV-2, has been elaborated. The derivatives were explored from the PubChem database. The obtained library of compounds was filtered through Lipinski’s rules, out of which, 74 obeyed the rule and were further subjected to molecular docking investigation against the SARS-CoV-2 replicase polyprotein 1a or pp1a (ID: 6LU7), with AutoDock Vina and iGEMDOCK. Deptropine possessed the highest binding affinity, in terms of released binding energy (-7.4 kcal/mol), against the SARS-CoV-2 replicase polyprotein 1a.