Chemistry Flashcards
Most abundant elements employed in mammalian biochemistry ?
C, N, O, H, S, P
But, augmented by a range of other elements – many of which are metals; I, Se,Cl, Na, K, Ca, Mg, Co, Cu, Ni, Zn, Fe, Mo, V
Many of the metals employed in mammalian biochemistry are associated with a protein . how many?
1/3 are metalloproteins
• Ionization energy equation?
A(g) > A+(g) + e-(g)
ionization energy increases or decreases across period?(left to right)
increase
ionization energy increase or decrease down a group?
decrease
Electron Affinity equation?
A(g) + e-(g) > A-(g)
elements towards….. of the period table have highest electron affinities?
top right
Electronegativity DEFINITION?
the ability of an atom within a compound to attract electrons towards itself.
Atoms of elements at the top left of the periodic table are the most electronegative. true or false
FALSE. TOP RIGHT
WHAT IS POLARIZABILITY?
underpins the idea of ‘Hard and Soft Lewis Acids and Bases’
-It is the ease with which an atom or ion can be distorted by an electric field.
• The hardest atoms and ions are those with high ionization energies – typically small atoms and ions near fluorine.
• The softest atoms and ions are those with low ionization energy and low electron affinity.
> Soft acids and bases are MORE/LESS polarizable and form bonds with more ‘COVALENT/IONIC character’.
Hard acids and bases are MORE/LESS polarizable and form bonds with more ‘COVALENT/IONIC character’.
MORE
COVALENT
LESS
IONIC
The biological roles performed by metals?
Structural
Catalytic
Redox
Other
The factors that influence the BIOLOGICAL role of the metal ?
- Valency.
- Ionic radius.
- Polarizability.
- Hydration energy (ease with which water molecules can be removed from the metal ion). • Radius of the hydrated ion.
explain lewis acid-base theory
• Broad definition of acids and bases that covered reactions that did NOT involve proton transfer.
• The theory allowed metal-ligand interactions to be described – ligand is the Lewis base and metal the Lewis acid.
Lewis Acids and Bases
• Lewis Acid – substance that accepts an electron pair
• Lewis Base – substance that donates an electron pair
• The theory states that ‘Hard Acids prefer Hard Bases’ while ‘Soft Acids prefer Soft Bases’
The most common coordination geometries found in biological systems are …………
…………..4 and 6 ( and 5).
• But as we’ll see, many metals are not fixed to only one coordination geometry.
coordination geometry number 4. name 2 geometries it can form
square planar
tetrahedral
coordination geometry number 6. name 1 geometry it can form
octahedral
a ligand can be monodentate or polydentate. explain both terms
- Monodentate – only one point of attachment to the metal.
- Polydentate – more than one point of attachment to the metal.
• Both types of ligand feature in biology, but the polydentate ligands are critical features of a range of important biological molecules.
- In a biological sense, these are a special case of polydentate ligands…
- A macrocyclic molecule is a ……………………?
a cyclic molecule (with at least 9 atoms), containing at least 3 donor atoms (Lewis base) – typically N, O, S or P.
are macrocyclic LIGANDS generally MORE OR LESS thermodynamically and kinetically stable than non-cyclic ligands.?
MORE T+K STABLE
Why are MACROCYCLIC LIGANDS more stable THAN NON-CYCLIC LIGANDS?
THE CHELATE EFFECT
• Simply stated, complexes with polydentate ligands will be more stable than complexes with similar monodentate ligands.
• Favourable entropic factor accompanying the release of nonchelating ligands from the metal ion.
• It is generally the case that stability increases with the number of donor atoms in the ring.
WHAT IS CHELATE?
a compound containing a ligand (typically organic) bonded to a central metal atom at two or more points.
BIOLOGICAL EXAMPLE OF MYCROCYCLIC LIGAND?
Porphyrin units (haem unit) of haemoglobin: N groups to iron metal in centre
WHAT IS CHELATE EFFECT?
the enhanced affinity of chelating ligands for a metal ion compared to the affinity of a collection of similar nonchelating (monodentate) ligands for the same metal
The clinical significance of chelation?
- Metal ions are widely distributed throughout the body.
- A range of drugs can behave as chelating ligands.
- Chelation changes both the physical and chemical characteristics of both components, i.e. the metal and the ligand.
give an example of a drug that works by chelation, what is it used for also?
- The Tetracyclines
- Broad-spectrum antibiotics – value has decreased over recent years due to resistance.
- Treatment of choice for certain infections: • Chlamydia. • Rickettsia. • Brucella. • Lyme disease. • respiratory and genital mycoplasma infections.
• Tigecycline: reserved for treatment of complicated skin and soft-tissue infections and complicated abdominal infections caused by multiple antibacterial resistant organisms.
explain mode of action of tetracyclines?-chelating
- Bacteriostatic agents.
- Target the 30S subunit.
- Selective – very little binding to mammalian ribosomes.
- Block binding of aminoacyl tRNA in the A-site.
- Involves Mg2+ ions»»»chelation
Drug interactions and safety of tetracyclines due to chelation?
• Not surprising that the absorption of the tetracyclines is affected by extent of chelation with metal ions.
• Most of the metal chelates are insoluble.
• The tetracyclines form chelates with a range of metal ions: Ca2+, Mg2+, Al3+, Fe2+, Zn2+
• With M3+ they form 3:1 drug-metal chelates.
• With M2+ they form 2:1 drug metal chelates.
• Iron (II): Ferrous sulfate, ferrous fumarate, and ferrous gluconate.
• Calcium (II): Calcium carbonate.
• Antacids and Antiulcer agents
-Aluminium and or magnesium hydroxide based antacids reduce the absorption of the tetracyclines
• An additional word about calcium:
• Tetracyclines are not recommended for children under the age of 12 due to discolouration of the teeth (ranges from greyish-brown to yellow). The effect is dose dependent and permanent»_space;>INCORPORATE W THE GROWING TEETH (MINERALS»GROWING TEETH- FORMING CHELATE. CANT BE BROKEN DOWN.
• Tetracyclines are also not recommended for pregnant or breast-feeding women – this is connected to the effect on skeletal growth»>DEPOSITING MINERALS> CHELATES.
- Study found that poly(ADP ribose) drives calcification of arteries.
- Working with Cycle Pharmaceuticals they showed that WHICH DRUG prevented the calcification?
minocycline
