Paper 4 Answers
James Day, Amy Thomson, Tamsin McAllister, Nawal Bahal in Get Through, 2014
Stereoisomerism is the existence of molecules with the same chemical constituents but different spatial arrangements. Geometric and optical are two forms of stereoisomerism. In optical stereoisomerism a chiral centre exists. This is either a carbon atom or a quaternary nitrogen atom. They have four bonds, with a different chemical group connected to each. This allows different arrangements of the chemical groups to the chiral centre. This produces molecules that are mirror images of each other and cannot be superimposed on each other. These mirror images are termed enantiomers. When prepared pharmaceutically, mixtures of these enantiomers are produced in equal proportions. This is termed a racemic mixture. Examples of drugs that are produced as racemic mixtures are the volatile anaesthetics (except sevoflurane), bupivacaine and atropine. Propofol and sevoflurane do not contain a chiral centre so have no enantiomers.
Alternative Modes of Tissue Coagulation and Removal
Sujoy K. Guba in Bioengineering in Reproductive Medicine, 2020
For this condition deep cooling and freezing is required so as to obtain tissue necrosis which appears over a period of hours following surgery and is complete in a few days. The necrotic tissue sloughs off with a fairly well demarcated margin from surrounding tissue which manifest minimal inflammatory reaction. A granulating base is left behind which either reepithelializes or forms a thin scar. Low temperature and heat transfer requirements are more stringent than for the cervical erosion application. Hence liquid nitrogen apparatus giving probe temperatures of -140 to -196 C are commonly used. Duration of application of the cooling device naturally has to be more than for cervical erosion so as to get a deep penetration into the tumor mass and duration of 5 minutes in each application is common. Longer periods tend to produce discomfort in the patient. Repeat treatment is the norm because in one sitting it is seldom possible to induce necrosis to full extent of a tumor. At a time depths up to 1.5 cm can be reached. Research has to be more than for cervical erosion so as to get a deep penetration into the tumor mass and duration of 5 minutes in each application is common. Longer periods tend to produce discomfort in the patient. Repeat treatment is the norm because in one sitting it is seldom possible to induce necrosis to the full extent of a tumor. At a time depths up to 1.5 cm can be reached.
Transportation of Bone Marrow for In Vitro Processing and Transplantation
Adrian P. Gee in BONE MARROW PROCESSING and PURGING, 2020
In addition to the regulations for the shipment of medical specimens, shipping of frozen bone marrow is covered by the regulations pertaining to the transportation of liquid nitrogen. Liquid nitrogen, having a temperature of below −130°C at atmospheric pressure, is defined as a cryogenic liquid.5Cryogenic liquids may not be transported in any container which has not been designed for temperatures at least as cold as the liquid which is being transported, i.e., liquid nitrogen cannot be transported in containers which have not been designed to hold liquids of −196°C or colder.The outer jacket on the liquid nitrogen shipping container must be constructed from steel.The design of the shipping container must allow for relief of pressure due to evaporation of the cryogenic liquid. This may be accomplished by installation of a suitable pressure relief valve or by a loose-fitting container cover.The outside of the container must be labeled with a label which reads “Nitrogen, Refrigerated Liquid”. Additionally, a label which reads “Nonflammable Gas” must be affixed to the shipping container. This latter label must be diamond-shaped and green in color, with a white border and white lettering (see Figure 2 for sample label).
Identification of structural fingerprints for in vivo toxicity by using Monte Carlo based QSTR modeling of nitroaromatics
Published in Toxicology Mechanisms and Methods, 2020
Dipayan Mondal, Kalyan Ghosh, Anurag T. K. Baidya, Anindita Mondal Gantait, Shovanlal Gayen
In the nitroaromatics, oxygen atoms bonded with nitrogen atom are more electronegative than nitrogen. This results in polarization of the oxygen–nitrogen bond and thus, nitro groups possess more electronegative character. As a result, nitro groups are themselves reduced by taking part in oxidation reactions and produce the biologically inert polymeric compounds, e.g. azo, azoxy compounds (Kulkarni and Chaudhari 2007). In our body, the normal functions of some proteins and DNA are blocked by the nitroaromatic compounds as these compounds can combine with the nucleophilic sites (examples –OH, −SH, and NH2 groups) through nucleophilic aromatic substitution (Katritzky et al. 2003). They can also form a complex with electron-donating heterocycles in biomolecules and may alter their normal function. In oxidative phosphorylation, they may also act as an uncoupling agent and may lead to a complex mechanism of toxicity (Donlon et al. 1995).
Synthesis, activity and mechanism of alkoxy-, carbamato-, sulfonamido-, thioureido-, and ureido-derivatives of 2,4,5-trimethylpyridin-3-ol against inflammatory bowel disease
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Chhabi Lal Chaudhary, Pallavi Gurung, Seoul Jang, Suhrid Banskota, Tae-Gyu Nam, Jung-Ae Kim, Byeong-Seon Jeong
Unfortunately, all alkoxy analogues (8a–8f) showed modest activity (29–67%) in our cell adhesion assay (Figure 2). Compound 8a (67% inhibition) and 8f (56% inhibition) showed 2.9- and 2.1-fold higher activity than the corresponding nitrogen counterparts whose inhibition level was 23% and 27%, respectively. Contrarily, compound 8e (29% inhibition) showed 2.5-fold less activity than the corresponding nitrogen counterpart (73% inhibition)18. The rest of alkoxy analogues with alkyl groups (8 b, 8c, 8d) did not show distinct activity from 6-alkylamino analogues. It seems that nitrogen atom does not necessarily be replaced and might be better to remain on C(6)-position for the better topological polar surface area (tPSA) and calculated partition coefficient (cLogP). By locating nitrogen back to C(6)-position, about 10% of both tPSA and cLogP values can be restored compared to the alkoxy analogues. Therefore, we decided to explore structural diversity with nitrogen atom on the position.
Structure activity relationship studies on Amb639752: toward the identification of a common pharmacophoric structure for DGKα inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Suresh Velnati, Alberto Massarotti, Annamaria Antona, Maria Talmon, Luigia Grazia Fresu, Alessandra Silvia Galetto, Daniela Capello, Alessandra Bertoni, Valentina Mercalli, Andrea Graziani, Gian Cesare Tron, Gianluca Baldanzi
From the data obtained, it is possible to identify some key pharmacophoric points crucial for the biological activity of the Amb compounds on DGKs namely: (i) a basic nitrogen; (ii) the methyl groups at the 2 and 6 position of the indole nucleus, and (iii) a (hetero)aromatic ring. This information allows us to build a four-point pharmacophoric model represented in Figure 11 superimposed with the minimised structure of compound 11. Although, we are not able to evaluate the importance of the two carbonyl groups, it represents the first attempts in order to identify the minimum structural request to interact with DGK catalytic site considering the molecular structure of the four most active inhibitors discovered to date (Amb639752, ritanserin, R59022, and R59949). We feel that this model might be useful to identify novel compounds active on DGKα through more targeted virtual screening campaigns, overcoming the current scaffolds.
Related Knowledge Centers
- Azo Compound
- Diatomic Molecule
- Nitrate
- Nitric Acid
- Hydrazine
- Pnictogen
- Standard Temperature & Pressure
- Asphyxiant Gas
- Pressure Swing Adsorption
- Liquid Nitrogen