PHD
  1. Inorganic chemistry  1.1. Coordination chemistry  1.1.1. Ligand field theory  1.1.2. Crystal field theory  1.1.3. Molecular Orbital Theory for Coordination Compounds  1.1.4. Stability of Coordination Compounds  1.1.5. Electronic spectra of coordination compounds  1.1.6. Isomerism in Coordination Compounds  1.1.7. Kinetics and mechanism of coordination reactions  1.2. Organometallic Chemistry  1.2.1. Metal Carbonyls  1.2.2. Metal alkyl and aryl  1.2.3. Fischer and Schrock carbonaceans  1.2.4. Oxidative Addition and Reductive Elimination  1.2.5. Metal Hydrides  1.2.6. Catalysis by organometallic compounds  1.2.7. Metallocenes and Sandwich Complexes  1.2.8. CH activation  1.3. Solid state chemistry  1.3.1. Crystal structures and lattices  1.3.2. Band theory and electrical properties  1.3.3. Defects in the crystal  1.3.4. Synthesis of solid state materials  1.3.5. Magnetic and optical properties of solids  1.3.6. Superconductivity  1.3.7. Solid state ionics  1.4. Bio-inorganic chemistry  1.4.1. Metalloproteins and enzymes  1.4.2. Metal ion transport and storage  1.4.3. The role of metals in medicine  1.4.4. Bioinspired catalysis  1.4.5. Metal–DNA interactions  1.4.6. Metal Complexes in Medical Science  1.5. Lanthanides and Actinides  1.5.1. Electronic configuration and oxidation states in lanthanides and actinides  1.5.2. Spectral and Magnetic Properties in Lanthanides and Actinides  1.5.3. Separation and Extraction of Lanthanides and Actinides  1.5.4. Coordination chemistry of f-block elements  1.6. Main Group Chemistry  1.6.1. Chemistry of boron compounds  1.6.2. Chemistry of Silicon and Germanium Compounds  1.6.3. Chemistry of Phosphorus and Sulfur Compounds  1.6.4. Organosilicon chemistry  1.6.5. Noble Gas Chemistry
  2. Organic chemistry  2.1. Reaction mechanism  2.1.1. Nucleophilic substitution reactions  2.1.2. Electrophilic addition and substitution reactions  2.1.3. Elimination reactions  2.1.4. Rearrangement reactions  2.1.5. Radical reactions  2.1.6. Pericyclic Reactions  2.1.7. Photochemical reactions  2.2. Stereoscopic  2.2.1. Chirality and optical activity  2.2.2. Structural analysis  2.2.3. Stereoelectronic effects  2.2.4. Asymmetric synthesis  2.2.5. Dynamic Stereochemistry  2.3. Organometallic Chemistry in Organic Synthesis  2.3.1. Organolithium and organomagnesium reagents  2.3.2. Transition metal catalyzed coupling reactions  2.3.3. Palladium-catalyzed reactions  2.3.4. Olefin Metathesis  2.3.5. Gold and silver catalysis  2.4. Natural products chemistry  2.4.1. Alkaloids and terpenoids  2.4.2. Steroids and Flavonoids  2.4.3. Total synthesis of natural products  2.4.4. Biosynthesis of natural products  2.5. Supramolecular Chemistry  2.5.1. Host-Guest Chemistry  2.5.2. Self-assembly and molecular recognition  2.5.3. Supramolecular Catalysis  2.5.4. Molecular Machines
  3. Physical Chemistry  3.1. Thermodynamics  3.1.1. Laws of Thermodynamics  3.1.2. Chemical Potential and Equilibrium  3.1.3. Statistical thermodynamics  3.1.4. Non-equilibrium thermodynamics  3.2. Quantum Chemistry  3.2.1. Schrödinger equation and its applications  3.2.2. Molecular orbital theory  3.2.3. Density functional theory  3.2.4. Post-Hartree–Fock methods  3.3. Chemical kinetics  3.3.1. Reaction rate theory  3.3.2. Mechanism and rate laws  3.3.3. Catalysis and enzyme kinetics  3.3.4. Reaction dynamics  3.4. Spectroscopy and molecular structure  3.4.1. Infrared Spectroscopy  3.4.2. UV-visible spectroscopy  3.4.3. Nuclear Magnetic Resonance Spectroscopy  3.4.4. Mass Spectrometry  3.4.5. Raman Spectroscopy  3.5. Surface and Colloid Chemistry  3.5.1. Absorption and Catalysis  3.5.2. Surfactants and micelles  3.5.3. Colloidal Stability  3.5.4. Nanomaterials and Interfaces
  4. Analytical chemistry  4.1. Chromatography  4.1.1. Gas Chromatography  4.1.2. High Performance Liquid Chromatography  4.1.3. Thin Layer Chromatography  4.1.4. Ion Chromatography  4.2. Electroanalytical techniques  4.2.1. Voltammetry and Polarography  4.2.2. Conductometry and potentiometry  4.2.3. Colometry  4.3. Spectroscopic Methods  4.3.1. Atomic absorption spectroscopy  4.3.2. Fluorescence Spectroscopy  4.3.3. X-ray diffraction  4.3.4. Electron paramagnetic resonance spectroscopy  4.4. Chemometrics  4.4.1. Data processing and statistical methods  4.4.2. Multidisciplinary analysis  4.4.3. Machine Learning in Analytical Chemistry
  5. Theoretical and Computational Chemistry  5.1. Molecular dynamics simulation  5.2. Quantum chemistry methods  5.3. Computational drug design  5.4. Machine Learning in Chemistry  5.5. Ab initio molecular dynamics
  6. Biophysics and Medicinal Chemistry  6.1. Drug discovery and design  6.2. Enzyme kinetics and inhibition  6.3. Chemical biology approach  6.4. Protein-ligand interactions  6.5. Bioorthogonal chemistry
  7. Materials chemistry  7.1. Polymer chemistry  7.1.1. Polymerization mechanism  7.1.2. Functional Polymers  7.1.3. Biodegradable Polymer  7.1.4. Conducting and semiconducting polymers  7.2. Nano Chemistry  7.2.1. Nanoparticles and nanostructures  7.2.2. Carbon-based nanomaterials  7.2.3. Quantum dots  7.3. Energy and Environmental Chemistry  7.3.1. Battery and Fuel Cell Chemistry  7.3.2. Green chemistry and sustainable materials  7.3.3. Photocatalysis

PHD → Biophysics and Medicinal Chemistry ↓


Drug discovery and design


Drug discovery and design is a broad process in biophysical and medicinal chemistry that focuses on identifying new drugs and creating new therapeutic compounds. The process integrates knowledge from chemistry, biology, and biophysics to develop drugs that can prevent, cure, or manage diseases. In this complex field, scientists work to understand the interactions between biological systems and chemical compounds to develop safer and more effective medicines. This text explores the fundamental principles, methods, and technologies employed in drug discovery and design.

Basics of drug discovery

Drug discovery begins with the identification of potential drug targets. These are primarily proteins, nucleic acids, or other biomolecules that play a key role in the disease process. Researchers focus on these targets to find ways to alter their function and alleviate disease symptoms. The next steps involve the identification, optimization, and validation of the lead compound through extensive research and testing.

Identifying drug targets

Drug targets are often discovered through basic biological research that elucidates disease mechanisms. Techniques such as genomic sequencing and proteomics help identify these targets by providing insights into gene expressions and protein functions. Let's look at an example of a drug target:

HER2 (human epidermal growth factor receptor 2)

HER2 is a protein involved in cell growth and division, and over-expression of HER2 is associated with certain types of breast cancer. By targeting HER2, drugs can inhibit cancer cell growth.

New approaches in drug discovery

Various innovative approaches have been developed to increase the accuracy and efficiency of identification of effective compounds in drug discovery. These methods include computer-aided drug design, high-throughput screening, and fragment-based drug discovery.

High-throughput screening (HTS)

HTS is a technique that allows the rapid evaluation of thousands to millions of compounds against a biological target. This automated process uses robotics and data processing software to test chemical libraries and quickly identify active compounds.

Compound A Compound B Compound C Compound D

Visualization: High-throughput screening tests many compounds.

Computer aided drug design (CADD)

CADD uses computational methods to simulate chemical interactions with biological targets. These simulations provide insight into molecular features that enhance efficacy, bioavailability, and safety.

Consider a drug that targets enzyme inhibition:

E = E + S ↔ ES → E + P

Here, E is the enzyme, S is the substrate, and P is the product. CADD helps us see how different compounds react with E to form ES complexes.

Medicinal chemistry in drug design

Medicinal chemistry is a major area of drug design that focuses on the chemical aspects of drug action. It involves the synthesis and chemical optimization of compounds identified as active leads. The process involves iterative cycles of designing, synthesizing, and testing to refine the efficacy and safety profile of the compound.

Lead optimization

Lead optimization refines compounds with promising activity against a biological target. This step adjusts molecular structures to improve properties such as potency, selectivity, and pharmacokinetics.

lead Customized Leads

Visualization: The lead optimization process shows the modifications to enhance the properties of the drug.

SAR studies (structure-activity relationship)

SAR studies analyze the relationship between chemical structure and biological activity. By changing different parts of the molecule, researchers determine which structural features affect the compound's activity.

For example, consider a basic structure:

C6H5-CH2-COOH (benzoic acid)

By modifying -CH2- group, its affinity for the receptor can be increased, thereby increasing its activity.

Role of biophysical chemistry

Biophysical chemistry provides information about the physical nature of how drugs interact with their biochemical environment. Techniques such as X-ray crystallography, nuclear magnetic resonance (NMR) and mass spectrometry (MS) are widely used.

X-ray crystallography

X-ray crystallography reveals the three-dimensional structures of biomolecules. Knowing the structure helps understand how drugs bind to targets at the atomic level, providing precise details for drug design.

Example:

Consider the crystalline structure of a protein:

Protein-ligand complex (4GS6)

This structure provides a detailed atomic arrangement, which is important for designing molecules that fit precisely into the active site.

NMR and MS in drug discovery

NMR provides information about the dynamics and interactions of molecules in solution, while MS helps to identify and quantify compounds and understand their structure and composition.

Preclinical and clinical development

Once a potential drug is identified and optimized, it undergoes preclinical testing in vitro and in animal models to assess its safety and efficacy. Successful candidates then proceed to clinical trials in humans, which include Phase I (safety), Phase II (efficacy and dosage), and Phase III (confirmation and comparison).

Regulatory and ethical aspects

The drug development process is governed by strict regulatory guidelines to ensure the safety and efficacy of new drugs. Agencies such as the FDA (Food and Drug Administration) and the EMA (European Medicines Agency) play a vital role in evaluating drugs before they are approved for the market.

Ethical considerations are paramount, particularly relating to clinical trial design, patient consent and transparent reporting of trial results. The integration of biophysics, chemistry and ethical guidelines ensures that drug development is carried out responsibly and effectively.

Conclusion

Drug discovery and design are complex but fascinating fields that combine various scientific disciplines to create new therapeutic agents. The methods and technologies used are constantly evolving due to advances in the chemical and biological sciences. The ultimate goal is to discover effective and safe drugs that improve patient outcomes and meet unmet medical needs. The challenges faced in this field drive innovation, promote a better understanding of disease mechanisms and open avenues for new treatments.


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Drug discovery and design

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