Lecture 1 : A brief introduction to Molecules of Life

Introduction to Organic Chemistry in Biology and Drug Design

Course Overview

• Professor Amit Basak from IIT Kharagpur introduces the NPTEL online certification course on Organic Chemistry in Biology and Drug Design. He will be the chief instructor, supported by research scholars for tutorials and queries.

Historical Context of Organic Chemistry

• The course begins with a historical perspective, highlighting Wohler's synthesis of urea from ammonium cyanate as a pivotal moment that challenged the belief that organic molecules only exist in living systems. This marked the inception of organic chemistry.

• Over two centuries, organic chemistry focused on isolating molecules from natural and synthetic sources, elucidating their structures, and understanding stereochemistry—the 3D arrangement of atoms within molecules.

Evolution of Organic Chemistry

• The field rapidly advanced with an emphasis on organic synthesis, leading to complex molecule creation through various reactions. Today’s organic synthesis is at its peak success level. The question arises: what comes next?

Intersection of Biology and Chemistry

• As organic chemistry evolved, biology also progressed—focusing on life processes at a macro level (organs, tissues) rather than molecular details until Linus Pauling's work on protein structure shifted this perspective towards molecular biology.

• Pauling introduced concepts like alpha helices in proteins; later, Watson and Crick revealed the double helix structure of DNA—signifying a new era where biological systems are examined at a molecular level involving primarily carbon-based compounds alongside other elements like hydrogen, nitrogen, oxygen, and phosphorus.

Role of Chemists Today

• Modern chemists must grasp not only fundamental aspects of organic chemistry (structure, function, reactivity) but also understand biological processes occurring within living systems since these involve similar chemical reactions as those performed in laboratories but under different environmental conditions.

• Biological reactions occur amidst numerous reactive molecules in living systems; they are orchestrated harmoniously by biological "carpenters" who synthesize or break down large molecules—a process crucial for maintaining health and preventing diseases when harmony is disrupted.

Understanding the Intersection of Chemistry and Biology

The Genesis of the Course

• The course aims to explore the chemistry within biological systems, emphasizing a molecular perspective on biological processes such as synthesis and breakdown.

• It highlights the necessity for chemists and biologists to collaborate, reflecting a shift in academic departments towards integrating chemistry with biology, as seen in Harvard's renaming of its department.

• The course will cover organic chemistry's relevance to biological systems, leading into drug design based on an understanding of these interactions.

Biological Molecules: An Overview

• Biological molecules are categorized into four main types: proteins, nucleic acids, lipids, and carbohydrates—collectively known as macromolecules.

• While most macromolecules are large structures formed from smaller units, some components like lipids may not qualify as macromolecules due to their lower molecular weight.

• Carbohydrates can vary significantly in size; they range from small sugars like glucose to larger polysaccharides like starch or cellulose.

Small Molecules and Their Importance

• In addition to major macromolecules, small and medium-sized molecules play crucial roles in cellular coordination through signal transduction processes.

• These signals facilitate communication between cells; small molecules often originate from other biological compounds through a process called biosynthesis.

• Biosynthesis refers specifically to the synthesis occurring within living organisms, distinguishing it from general chemical synthesis.

Building Blocks of Life: Proteins

• Proteins are primarily composed of amino acids. Understanding their structure is essential for grasping how they function biologically.

• Amino acids that form proteins are classified as alpha amino acids due to their specific structural characteristics involving an amine group adjacent to a carboxylic acid group.

Chiral Centers in Amino Acids

• Alpha amino acids contain stereogenic centers (chiral centers), allowing them to exist in two enantiomeric forms; however, only L-amino acids are utilized by living organisms for protein synthesis.

• This specificity underscores the importance of chirality in biochemical processes and protein formation.

Understanding Amino Acids and Their Properties

Components of Proteins

• Proteins are primarily composed of L-alpha amino acids, with a total of 20 different amino acids identified.

• Glycine is unique among amino acids as it is achiral due to its non-stereogenic carbon (R group being hydrogen).

• The D, L nomenclature for amino acid configuration is older; biologists still use it despite the R, S system being more common in organic chemistry.

• Most chiral amino acids have an S configuration, except for cysteine which has a different configuration.

Acidic and Basic Properties

• Amino acids contain both basic (amine group) and acidic (carboxylic acid group) functionalities, allowing for internal hydrogen transfer.

• In an acidic medium (pH 1), the amine group becomes protonated (NH3+), while the carboxylic acid remains as CO2H due to its pKa value.

• As pH increases, the carboxylic acid loses a proton first because it has a lower pKa compared to the amine's proton.

Zwitterion Formation

• The zwitterion structure forms when both positive and negative charges coexist within an amino acid at specific pH levels.

• The charge fluctuates from +1 to -1 through the zwitterion form, which has no net charge and does not migrate in an electric field.

Isoelectric Point (pI)

• The pH at which an amino acid exists predominantly in its zwitterion form is known as the isoelectric point (pI).

• The formula for calculating pI is: textpI = frac(textpK_1 + textpK_2)2 , where pK values correspond to dissociation constants.

Classification of Amino Acids

• Amino acids can be classified based on their R groups; those with non-polar R groups are termed non-polar amino acids.

• Examples include alanine with a methyl group and valine with an isopropyl group.

Understanding Amino Acids and Their Properties

Types of Amino Acids

• Non-polar amino acids have side chains that are hydrophobic, meaning they do not interact well with water.

• Polar groups in amino acids can form hydrogen bonds due to the presence of electronegative atoms like oxygen or sulfur, which creates a dipole moment.

• Amino acids such as glutamic acid contain acidic functionalities in their side chains, characterized by additional carboxy groups.

• Aspartic acid is a homolog of glutamic acid with one less carbon, also classified as an acidic amino acid.

• Basic amino acids include those with NH2 or imidazole groups; lysine and arginine are strong bases while histidine is weaker.

Classification and Functions of Proteins

• The four major classes of biological macromolecules include proteins, nucleic acids, carbohydrates, and lipids.

• Small molecules generated within the body or obtained from diet play essential roles in maintaining life alongside these macromolecules.

• Proteins consist mainly of L-alpha amino acids (except glycine), linked by amide bonds to form diverse structures and functions.

• Different proteins serve various functions: enzymes for catalysis, structural proteins like collagen for muscle maintenance, and hormones such as insulin.

• The isoelectric point is crucial for determining the charge of proteins at specific pH levels.