Graduate
  1. Physical Chemistry  1.1. Thermodynamics  1.1.1. Laws of Thermodynamics  1.1.2. Enthalpy and heat capacity  1.1.3. Entropy and free energy  1.1.4. Phase Equilibrium  1.1.5. Statistical thermodynamics  1.1.6. Thermodynamic cycle  1.1.7. Fugacity and activity  1.2. Quantum Chemistry  1.2.1. Principles of quantum mechanics  1.2.2. Schrödinger Equation  1.2.3. Particle in a box  1.2.4. Operators and eigenvalues  1.2.5. Atomic orbitals  1.2.6. Molecular orbital theory  1.2.7. Perturbation theory  1.2.8. Valence bond theory  1.2.9. Hybridization and chemical bonding  1.3. Chemical kinetics  1.3.1. Rate laws and reaction mechanisms  1.3.2. Collision theory  1.3.3. Transition state theory  1.3.4. Enzyme Kinetics  1.3.5. Chain Reactions and Polymerization  1.3.6. Photochemical reactions  1.4. Statistical mechanics  1.4.1. Partitioning functions  1.4.2. Molecular distribution functions  1.4.3. Boltzmann Distribution  1.4.4. Bose–Einstein and Fermi–Dirac statistics  1.5. Spectroscopy  1.5.1. Rotational Spectroscopy  1.5.2. Vibrational Spectroscopy  1.5.3. Electronic Spectroscopy  1.5.4. Nuclear magnetic resonance spectroscopy  1.5.5. Mass Spectrometry  1.5.6. Raman Spectroscopy  1.5.7. Electron paramagnetic resonance spectroscopy  1.6. Surface and colloidal chemistry  1.6.1. Absorption isotherm  1.6.2. Surface tension and wetting  1.6.3. Colloidal Stability  1.6.4. Catalysis  1.6.5. Emulsions and micelles  1.7. Electrochemistry  1.7.1. Nernst equation  1.7.2. Electrochemical cells  1.7.3. Conductivity and mobility  1.7.4. War  1.7.5. Fuel cells  1.7.6. Electrolysis
  2. Organic chemistry  2.1. Reaction mechanism  2.1.1. Nucleophilic substitution reactions  2.1.2. Electrophilic addition reactions  2.1.3. Elimination reactions  2.1.4. Rearrangement reactions  2.1.5. Radical reactions  2.1.6. Pericyclic reactions  2.2. Spectroscopy and structural determination  2.2.1. UV-Vis Spectroscopy  2.2.2. IR Spectroscopy  2.2.3. NMR Spectroscopy  2.2.4. Mass Spectrometry  2.2.5. X-ray crystallography  2.3. Stereoscopic  2.3.1. Chirality and optical activity  2.3.2. Structural analysis  2.3.3. Geometrical isomerism  2.3.4. Dynamic Stereochemistry  2.4. Organometallic Chemistry  2.4.1. Organolithium and organomagnesium reagents  2.4.2. Palladium-catalyzed cross-coupling reactions  2.4.3. Transition Metal Complexes  2.4.4. Metal–carbon bond  2.5. Polymer chemistry  2.5.1. Polymerization mechanism  2.5.2. Polymer Characteristics  2.5.3. Biodegradable Polymer  2.5.4. Conducting polymer  2.5.5. Supramolecular polymers  2.6. Medicinal chemistry  2.6.1. Drug design and development  2.6.2. Pharmacokinetics and pharmacodynamics  2.6.3. Structure-activity relationships  2.6.4. Molecular docking and drug screening
  3. Inorganic chemistry  3.1. Coordination chemistry  3.1.1. Crystal field theory  3.1.2. Ligand field theory  3.1.3. Spectrochemical Series  3.1.4. Chelation and stability  3.2. Organometallic Chemistry  3.2.1. Metal Carbonyls  3.2.2. Catalysis by organometallic complexes  3.2.3. Metallocenes  3.3. Bio-inorganic chemistry  3.3.1. Metalloproteins and enzymes  3.3.2. The role of metals in biological systems  3.3.3. Metal ion transport and storage  3.4. Solid state chemistry  3.4.1. Crystal Structures  3.4.2. Band theory of solids  3.4.3. Superconductors  3.4.4. Defects in the crystal  3.5. Lanthanides and Actinides  3.5.1. Electronic configuration in lanthanides and actinides  3.5.2. Coordination chemistry of the lanthanides  3.5.3. Magnetic Properties of Lanthanides
  4. Analytical chemistry  4.1. Chromatography  4.1.1. Gas Chromatography  4.1.2. High Performance Liquid Chromatography  4.1.3. Thin Layer Chromatography  4.2. Spectroscopic Techniques  4.2.1. Atomic absorption spectroscopy  4.2.2. X-ray diffraction  4.2.3. Inductively coupled plasma spectroscopy  4.3. Electroanalytical methods  4.3.1. Potentiometry  4.3.2. Voltammetry  4.3.3. Colometry  4.4. Mass Spectrometry  4.4.1. Ionization Technique  4.4.2. Fragmentation Pattern  4.5. Chemometrics  4.5.1. Multidisciplinary analysis  4.5.2. Machine Learning in Chemistry
  5. Theoretical and Computational Chemistry  5.1. Molecular dynamics simulation  5.1.1. Force fields and energy minimization  5.1.2. Monte Carlo simulation in molecular dynamics simulations  5.2. Quantum chemical methods  5.2.1. Hartree–Fock theory  5.2.2. Density functional theory  5.2.3. Semi-empirical methods  5.3. Computational drug design  5.3.1. Molecular Docking  5.3.2. QSAR Modeling  5.3.3. Virtual Screening
  6. Biochemistry  6.1. Enzyme Kinetics  6.1.1. Michaelis-Menten kinetics  6.1.2. Inhibition mechanism  6.2. Metabolism and Bioenergetics  6.2.1. Glycolysis  6.2.2. Citric acid cycle  6.2.3. Electron transport chain  6.3. molecular Biology  6.3.1. DNA replication and repair  6.3.2. Protein synthesis  6.3.3. Gene Regulation  6.4. Structural Biochemistry  6.4.1. Protein Folding  6.4.2. Membrane Biophysics
  7. Environmental Chemistry  7.1. Atmospheric Chemistry  7.1.1. Greenhouse gases  7.1.2. Ozone depletion  7.1.3. Air pollutants and smoke  7.2. Water Chemistry  7.2.1. pH and water hardness  7.2.2. Wastewater treatment  7.2.3. Aquatic Chemistry  7.3. Soil Chemistry  7.3.1. Heavy metal contamination  7.3.2. Soil pH and Buffering  7.3.3. Nutrient cycling  7.4. Toxicology and Chemical Safety  7.4.1. Toxicokinetics  7.4.2. Risk Assessment in Toxicology and Chemical Safety in Environmental Chemistry  7.4.3. Effects of pollutants on the environment

Graduate → Organic chemistry ↓


Medicinal chemistry


Medicinal chemistry is a discipline based on a combination of chemistry and pharmacology that is involved in the design, synthesis, and development of pharmaceutical agents or drugs. It combines the power of organic chemistry with the insights of pharmacology to understand how chemical structure affects biological activity. At the undergraduate chemistry level, medicinal chemistry is a broad subject, delving deeply into the principles of organic chemistry to design molecules that can modify biological pathways.

Fundamentals of medicinal chemistry

One of the fundamental principles of medicinal chemistry is the structure-activity relationship (SAR), which explores how the chemical structure of a compound affects its biological activity. To understand SAR, chemists closely observe how changing different parts of a molecule can increase or decrease its effectiveness as a drug.

Structure-activity relationship (SAR)

The SAR approach is fundamental to designing new therapeutic agents in medicinal chemistry. It involves systematically modifying the chemical structure of a known active compound to improve efficacy, reduce side effects or increase selectivity.

For example, consider the following modification of a simple aromatic compound where the hydroxyl group (-OH) can be replaced by a methoxy group (-OCH3) to increase lipid solubility:

 
    Basic Structure:
        benzene-OH

    Revised Structure:
        Benzene- OCH3

In this instance, the change from a hydroxyl to a methoxy group may increase the compound's ability to penetrate cell membranes, which is essential for its activity within the body.

Pharmacophores and bioisosterism

Another important concept in medicinal chemistry is the identification of the pharmacophore. A pharmacophore is the set of static and electronic features that are required to ensure optimal interaction with a specific biological target to trigger a biological response.

Chemists often use the concept of bioisosterism to design new medicines. A bioisostere is a chemical substituent or group that has similar physical or chemical properties that produce broadly similar biological properties to another chemical compound. This approach may be essential in improving a drug's efficacy or reducing side effects.

NH 2 CH 3 NH

In the above example, replacing the amine group (-NH2) with a methylamine group (-CH3 NH) can modify the interaction of the compound with the target protein without significantly changing the overall properties of the compound.

Role of organic chemistry

Organic chemistry is the backbone of medical medicinal chemistry. For drug design and development, a comprehensive understanding of functional groups, stereochemistry and molecular geometry is essential.

Functional groups in drug design

Functional groups play an important role in the behavior of pharmaceutical compounds. The presence or absence of specific functional groups can substantially alter the pharmacokinetic and pharmacodynamic properties of a drug.

Consider the difference between two common functional groups:

-OH (alcohol) -COOH (carboxylic acid)

Alcohol groups (-OH) can increase water solubility and form hydrogen bonds with target molecules. Carboxylic acids (-COOH) can participate in deprotonation reactions and provide anchoring points at enzyme active sites.

Stereochemistry in drug molecules

Stereochemistry refers to the spatial arrangement of atoms in molecules and significantly affects drug action and metabolism. Many drugs exist as enantiomers — molecules that are mirror images of each other.

Enantiomers can have very different effects in biological systems. Often, one enantiomer is more biologically active than the other, which is why stereochemical considerations are important during drug design.

 
    Example of enantiomers:
        
    (R)-Ibuprofen (S)-Ibuprofen

    The two enantiomers have different pharmacological effects, with the (S)-enantiomer being the more active form for pain relief.

Understanding drug metabolism

Another important aspect of medicinal chemistry is metabolism - the process by which drugs are transformed within the body. Understanding metabolism is crucial for the effective design of drugs with appropriate efficacy and safety profiles.

During drug metabolism, functionalization reactions such as oxidation can convert the parent drug into metabolites, which may be active or inactive depending on their ability to bind to the intended target. The liver is the primary site for drug metabolism.

Phase I and Phase II reactions

Drug metabolism typically involves phase I and phase II reactions:

  • Phase I reactions: These are functional reactions, such as oxidation, reduction, and hydrolysis. They introduce or expose functional groups, such as hydroxyl, leading to a more water-soluble (and often inactive) form of the drug.
  • Phase II reactions: These are conjugation reactions in which endogenous molecules (e.g., glucuronic acid, sulfate, amino acids) are incorporated into the drug or its Phase I metabolites. This process further increases solubility, thereby promoting renal excretion.
Original drug Step 1 Phase II metabolite Phase II

Understanding these metabolic pathways is important because it helps medicinal chemists predict the potential effects of drugs and design molecules that optimize desirable aspects while minimizing adverse consequences.

Design and development of medicinal compounds

Designing new medicinal compounds requires a mix of creativity and scientific knowledge. Starting with a lead compound — a chemical compound that shows pharmacological or biological activity that is likely to be therapeutically useful — chemists systematically modify it to improve potency, selectivity, and pharmacokinetic properties.

 
    Drug Development Process:
        
    1. Identify the targeted disease or condition
    2. Detection and identification of lead compounds
    3. Optimization of Lead Compounds
    4. Preclinical studies
    5. Clinical trials

Throughout this process, various rounds of iteration improve the pharmacological properties of potential drugs, ensuring that the most promising compounds move forward to clinical testing.

Rational drug design

Rational drug design is a strategy that is based on structure-based design or ligand-based design. It relies on understanding the 3D structure of target biological molecules (such as enzymes or receptor proteins) in order to design molecules that will specifically interact with these targets.

Knowledge of a compound's binding affinity, efficacy, and toxicity guides the rational drug design process. Tools such as X-ray crystallography and NMR spectroscopy help map interactions at the molecular level, which aids in refining key compounds.

Example: Designing an enzyme inhibitor

Enzyme inhibitors are a popular type of drug due to their ability to block specific biochemical reactions. When designing inhibitors, it is important to understand the active site of the enzyme.

 
    Enzyme targets (simplified):
        
    Active site: serine hydrolase

    Blocker Design:
    - Reactive group: fluorophosphate
    - Interaction: covalent bond with serine at the active site

In this example, a designed inhibitor can form covalent bonds with the active hydrogen at the enzyme's active site, effectively blocking its activity.

Challenges and future directions

The challenges of medicinal chemistry include predicting and managing off-target effects, drug resistance, and optimizing drug delivery. Ongoing advances in computational chemistry and biotechnology continue to present new opportunities for the discovery and design of new therapeutic agents.

Emerging technologies

Approaches such as drug repurposing, application of machine learning for compound activity prediction, and targeted drug delivery modules promise to transform the field of medicinal chemistry.

Advances in personalised medicine and genomic information have also provided exciting avenues for designing drugs that are tailored to the genetic profiles of individual patients, marking a transformational shift in our approach to treatment and therapy.

In conclusion, medicinal chemistry is a dynamic field that combines organic chemistry with biological insights to discover and design drugs that promote healthier, longer lives. As technology and scientific understanding advance, the potential to generate more sophisticated and effective therapies becomes increasingly promising.


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Medicinal chemistry

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