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 ↓


Bioorthogonal chemistry


Bioorthogonal chemistry refers to chemical reactions that can occur inside living systems without interfering with the basic biochemical processes. These reactions are designed to remain inactive in the presence of the complex environment of biological molecules in the cellular environment. This concept has been revolutionary in the fields of chemical biology and medicinal chemistry, providing scientists with a set of tools that enable them to explore and manipulate biological molecules in their natural context.

The term "bioorthogonal" was coined by Carolyn Bertozzi to describe reactions that are inert to natural cellular processes. These reactions open up the possibility to image, tag, or manipulate molecules within living cells or living organisms by remaining selectively reactive even amid the high complexity of biomolecules.

Fundamentals of bioorthogonal chemistry

In traditional chemistry, reactions are often carried out in vitro under controlled conditions. Inside a living cell, this level of control is not possible due to the presence of many reactive biomolecules such as proteins, nucleic acids, lipids, and carbohydrates. Thus, bioorthogonal reactions must satisfy several criteria:

  • Inertness to biological molecules.
  • The kinetics are fast enough that significant labeling can be achieved in a reasonable time.
  • Specificity towards bioorthogonal pairs without cross-reactivity.
  • Non-toxic to living cells.

These criteria ensure that bioorthogonal chemistry can be employed in complex biological settings without disrupting normal cellular functions.

Popular bioorthogonal reactions

Many types of reactions have been adapted and used as bioorthogonal devices. Below are some classic examples:

1. Copper-catalyzed azide-alkyne cycloaddition (CuAAC)

RN 3 + R'-C≡CH → RN 3-CR' (in the presence of Cu +)
Azide (RN 3) Alkynes (R'-C≡CH) Triazole Products

This reaction, often called "click chemistry", takes advantage of the high reactivity between azides and alkynes in the presence of a copper catalyst. The result is a 1,2,3-triazole linkage that is stable and can be used to connect a variety of molecular entities. One limitation, however, is the potential toxicity of copper to cells, which requires careful optimization of conditions.

2. Strain-promoted azide-alkyne cycloaddition (SPAAC)

RN 3 + R'-C=C: → RN 3-R' (no catalyst required)
Cycloaddition products

SPAAC is a copper-free alternative to CuAAC, which uses the strain energy of cyclic alkynes to facilitate the reaction with azide without a catalyst. This makes it particularly useful for live-cell applications where copper ions could be harmful.

Applications in biophysical chemistry

The ability to make chemical modifications on the spot has a profound impact on biophysical studies. Some applications include:

Fluorescent labeling

Bioorthogonal reactions enable fluorescent probes to be attached to specific biomolecules, allowing us to visualise the dynamics and distribution of these molecules in living cells. This could be particularly useful for tracking the movement and localisation of proteins or nucleic acids over time.

Biomolecule tracking

By tagging molecules with bioorthogonal handles, researchers can follow these components through complex biological pathways to understand mechanisms of action or identify key interaction sites.

Applications in medicinal chemistry

Bioorthogonal techniques have provided innovative solutions to challenges in drug design and development. Some of the major applications are as follows:

Targeted drug delivery

Bioorthogonal reactions can be used to deliver drugs specifically to diseased cells by using targeting ligands that bind to cell-surface markers present only on these cells.

Prodrug activation

Prodrugs are inactive compounds that can be activated by specific biochemical processes in the body. Using bioorthogonal chemistry, prodrugs can be converted into their active forms specifically at their site of action, thereby reducing side effects.

Future directions and challenges

Bioorthogonal chemistry is a rapidly evolving field, with continuous efforts being made to develop new reactions that meet the stringent requirements of biocompatibility and selectivity. The quest to expand the scope by developing faster, more selective and more biocompatible reactions continues. However, there are certain challenges inherent in achieving this goal. These include the need to:

  • Reactions with extraordinary speed require the ability to function effectively in dynamic biological systems.
  • Reaction partners that are readily available or that can be easily incorporated into biological systems.
  • further reducing the potential cytotoxicity of reaction components and by-products.

As the field advances, future work will likely focus on integrating bioorthogonal techniques with emerging technologies such as CRISPR or nanoparticle-based drug delivery systems, thereby expanding the toolset available to molecular biologists and chemists.

Bioorthogonal chemistry is evidence of the profound impact that innovations at the chemistry-biology interface can achieve, opening doors to probe and intervene in living systems in unprecedented ways.


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Bioorthogonal chemistry

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