ACCM Concepts This Exemplar will teach the following concept(s) from the ACS Examination Institute General Chemistry (ACCM): III.B Models exist that allow the prediction of the shape of chemicals about any bonding atom in a molecule. IV.C Intermolecular forces can be categorized based on the permanence and structural details of the dipoles involved. IV.D For condensed phases that are not structures of extended chemical bonds, the physical properties of the state are strongly influenced by the nature of the intermolecular forces. Background Molecules exhibit unique characteristics and interact differently with other molecules based on their geometric structure. In this piece, we will explore how the drug Albuterol reinforces this notion. Albuterol is a drug used to treat Asthma attacks 3 . Asthma is characterized by the lack of proper airflow due to constricted airways 7 . To relieve the constriction of the airways, the affected person must use an inhaler to deliver a fast-acting medication that opens the airways 7 . There are two types of asthma medications: relievers and preventers 6 . Relievers, such as Salbutamol, are taken during an asthma attack to cause immediate relief of asthma symptoms 6 . Preventers, like Budesonide, reduce the inflammation that causes constricted airways 6 . For the purposes of this chapter, we will be focusing on the geometric characteristics and behavior of relieving drugs, such as Salbutamol. Overview of Albuterol (Salbutamol) Albuterol is used to rapidly treat asthmatic symptoms. Albuterol’s “rescue” capabilities are attributed to its classification as a short-acting beta agonist (SABA). Understanding why Albuterol is considered a SABA involves understanding the chemistry behind the mechanism, which is only possible by first comprehending the pharmacology. The dilation of the airways is controlled by the smooth muscles surrounding them 4 . The contraction and relaxation of these muscles are controlled by the beta-2 and muscarinic receptors respectively 2 . These receptors are located in various places in the body, but Albuterol only interacts with the receptors within the body’s main airways: the trachea, bronchioles, and lungs. Albuterol is referred to as a beta-2 agonist; it activates the beta-2 receptors while inhibiting the muscarinic receptors, which forces the smooth muscles to relax and causes the airways to widen 2 . There are two general methods of synthesizing the drug based on two starting materials: substituted benzophenones and salicylic acid derivatives 1 . Albuterol is synthesized to specifically stimulate beta-2 adrenoceptors—leaving beta-1 adrenoceptors unaffected 1 . This is important because beta-1 receptors directly affect the constriction of heart vessels 1 . Albuterol differs from other sympathomimetics—drugs that produce physiological effects by promoting the stimulation of sympathetic nerves—in that the hydroxyl group on the third carbon of the aromatic ring is replaced with a hydroxymethyl group 1 . This difference causes a distinction because, it changes the shape of the molecule, allowing Albuterol to interact with the beta-2 adrenoceptors specifically. Albuterol’s Molecular Geometry Albuterol’s chemical formula is C 13 H 21 NO 3 5 . The molecule can be depicted by the molecule below(Figure 1). Figure 1. 3D Visualization of Albuterol 8 The structure shown has many different molecular geometries ranging from tetrahedral to bent 8 . These molecular geometries all play a role in how the albuterol molecule interacts with only the beta-2 receptors in the trachea, bronchioles, or lungs 1 . It is important to understand that the synthesis of albuterol to reflect this structure is not accidental. Though we will not delve into the mechanisms behind the formation of the drug, it is important to recognize that it is deliberately synthesized to have certain geometric characteristics and bond angles—making the drug exclusive to beta-2 receptors. These carefully calculated bond angles make it so that albuterol exclusively reacts with one receptor in a specific way. Example \(\PageIndex{1}\) Which molecule has the strongest bonds between Sulfur and Oxygen? SO 2 or SO 3 ? Solution SO 2 has the strongest bonds because of it’s higher bond order and higher number of double bonds. Also, when comparing the electron geometry and molecular geometry, both molecules have the same electron geometry: trigonal. However, SO 2 is a more favored molecule because it’s bond angles are closer to 109.5° than the bond angles in SO 3 which are 120°. This shows that despite two molecules having a very similar composition and the same electron geometry, their ability to form different bonds and orient themselves differently around the central atom can cause drastic changes in their behavior. References (3) How is asthma treated? | aafa. Org . https://www.aafa.org/asthma-treatment/ (accessed 2022-11-10). (2) W hat does an inhaler do? | how do asthma inhalers work? . Cure Allergy Clinic. https://www.cureallergyclinic.com/bl...nhalers-work-/ (accessed 2022-11-10). (3) The chemistry of asthma inhalers . Compound Interest. https://www.compoundchem.com/2014/11/25/asthma/ (accessed 2022-11-10). (4) Johnson, D. B.; Merrell, B. J.; Bounds, C. G. Albuterol. In StatPearls ; StatPearls Publishing: Treasure Island (FL), 2022. (5) Barnes, P. J. Biochemical Basis of Asthma Therapy. J Biol Chem 2011 , 286 (38), 32899–32905. https://doi.org/10.1074/jbc.R110.206466 . (6) Albuterol - an overview | sciencedirect topics . https://www.sciencedirect.com/topics...late%20cyclase . (accessed 2022-11-10). (7) PubChem. Salbutamol . https://pubchem.ncbi.nlm.nih.gov/compound/2083 (accessed 2022-12-07).(8) WebMO . https://www.webmo.net/ (accessed 2022-12-07). (8) WebMO . https://www.webmo.net/ (accessed 2022-12-07).