An introduction to inorganic chemistry 1+2 Flashcards
what are the 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
What are many of the metals associated with
a protein - 1/3 of proteins are metalloproteis
what does each period correspond to?
the completion of the s and p subshells
what happens to atomic radii down a group and across a period (left to right)
increases down a group and from left to right across a period
what happens to ionisation energy across the 1st period?
across the 1st period ionisation energy increases left to right
what is electron affinity
is is a measure of how strongly an atom or molecule can attract an extra
electron
what is electronegativity?
the ability of an atom within a compound to attract electrons towards itself
what is polarisability?
the essentially 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.
what are the hardest atoms and ions?
the hardest atoms and ions are those with low ionisation energy and low electron affinity
what are the softest atoms and ions
those with low ionisation energy and low electron affinity
soft acids and bases are
more polarisable and form bonds with more covalent character
what are the biological roles performed by metals
structural
catalytic
redox
other
hard acids and bases are
less polarisable and form bonds with more ionic character
what are the factors that influence the role of the metal
valency, ionic radius, polarisability
hydration energy (ease with which water molecules can be removed from the metal ion).
radius of the hydrated ion.
Lewis acids and bases
theory introduced by the American chemist G.N Lewis
what does the theory state
that hard acids prefer hard bases while soft acids prefer soft bases
what did this theory allow?
metal ligand interactions to be described- ligand is the Lewis base and metal the Lewis acid
define a Lewis acid
substance accepts an electron pair
define Lewis base
substance that donates an electron pair
properties of hard acids
high charge density
small ionic radius
not easily polarisable
Na+, K+, Mg2+, Ca2+, Fe3+, Co3+
Properties of hard bases
not easily polarised
high electronegativity
vacant, high energy orbitals
hard to oxidise
H2O,-OH, CO2-, CO22- , NO-3, PO3- 4, ROH, RO-, R2O, NH3, RNH2, CL-
Acid intermediate
Fe2+, Co2+,Ni2+, Cu2+, Zn2+
base intermediate
NO-2, Br-, Imidazole
soft acid
low charge density
large ionic radius
more polarisable Cu+
soft base
high polarisability
low electronegativity
low energy vacant orbitals easily oxidised RSH, RS-, CN-, CO
shape of a molecule can be defined by ?
bonds electron pairs within it so it is possible to predict the geometry of coordination compounds.
linear
2 numbers of pairs
alkyne (sp)
Equilateral triangle
alkene sp2
3 numbers of pairs
tetrahedron
alkane sp3
3 numbers of pairs
trigonal bi-pyramidal square pyramid (less stable)
AsF5 sp3d
5 numbers of pairs
octahedron
6 numbers of pairs
SF6 sp3d
what do different metals prefer?
different coordination numbers ( different numbers of ligands bonded to the metal)- hence, different geometries
what are the most common coordination geometries found in biological systems?
4 and 6 and 5
are many metals fixed to only one geometry
are not fixed to only one coordination geometry
what are the common geometries
tetrahedral
square planar
octahedral
what can ligands be
monodentate or polydentate
define polydentate
more than one point of attachment to the metal
define monodentate
only one point of attachment to the metal
what types of ligands feature in biology
both types of ligand feature in biology, but the polydentate ligands are critical features of a range of important biological molecules
examples of ligands
copper glycine
ciprofloxacin
EDTA
what are macrocyclic ligands
in biological sense, these are a special case of polydentate ligands
a macrocyclic molecule is a cyclic molecule with at least 9 atoms containing at least 3 donor atoms Lewis base typically N, O, S or P
are macrocyclic complexes generally thermodynamically and kinetically more stable than non-cyclic ligands
yes they are
why are they more stable
essentially its the chelate effect
simply stated, complexes with polydentate ligands will be more stable than complexes with similar mono dentate 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
biological examples
the porphyrin unit
a simplified haem unit
what’s 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 ie the metal and the ligand
what is the clinical significance of chelation
the tetracyclines
broad spectrum antibiotics - value has decreased over recent years due to resistence
treatment of choice for certain infections
-chlamydia
rickettsia
brucella
Lyme disease
also 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
what is the tetracyclines mode of action?
bacteriostatic agents
tagets 305 subunit
selective -very little binding to mammalian ribosomes
block binding of aminoacyl tRNA in the A-site
involving Mg2+ ions
examples of tetracyclines
doxycycline , monocycline
oxytetracycline, tetracycline demeclocycline
are most metal chelates insoluble?
yes most of the metal chelates are insoluble
what is absorption of tetracyclines affected by?
extent of chelation with metal ions
tetracyclines form what?
form chelates with a range of metal ions Ca2+, Mg2+, Al3+, Fe2+, Zn2+
with M3+ what is produced?
they form 3:1 drug-metal chelates
with M2+ what is produced ?
2:1 drug metal chelates
iron (II)
ferrous sulfate , ferrous fumarate and ferrous gluconate
calcium (II)
calcium carbonate
What do aluminium and or magnesium hydroxide based antacids do?
reduce the absorption of the tetracyclines
who cannot have tetracyclines
not recommended for children under the age of 12 due to discolouration of the teeth (ranges from greyish to yellow) the effect is dose dependent and permanent
tetracyclines are also not recommended for pregnant or breast feeding women - this is connected to the effect on skeletal growth
what isa key aspect of metal ions ?
in their ability to stabilise conjugate bases
what does this do to the pka of the parent acid
it is frequently lowered
what is calmodulin?
proteins involved in the meditation of the Ca2+ signal in large number of pathways sometimes found as part of enzyme complexes phosphorylase kinase
describe calmodulin?
small acidic protein
dumbbell shaped protein that binds 4x Ca2+ ions
the major donor groups from the protein that bind to the Ca2+ ions are carbonyl and carboxylate groups binding is complex involving a specific set of Lewis bases so as not to stabilise cross-links within the protein.
key properties of Ca2+ ions
binding- it is selective but differs from Mg2+ ion in a number of key ways can interact with neutral oxygen donors carbonyls and ethers
it can bind to a number of centres at once - irregular coordination geometry
ligands- Ca2+ ions readily exchange water with other ligands - with a complex, the ligands on the ion are fluctional
Ca2+ and its biological roles
metabolism- numerous enzymes inside cells
cell division- S-100 proteins, immune system
cell death (apoptosis)- internal proteases
binding to membranes- C-2 domains of enzymes
Phosphorylation -activation of kinases involved in fertilisation of the egg
hormone transmitter release- homeostasis
blood clotting- involved in both the intrinsic and extrinsic pathways
Mg2+ ions and DNA/RNA
although the role of Mg2+ ions in a number of RNA/DNA units is significant , it is perhaps its role in tRNA and ribosomes that are amongst the most important
tRNAs contain regions known as?
half crucifixs
Mg2+ ions are key to holding this shape
what do ribozymes require Mg2+ ions to do ?
catalyse their splicing reactions
what is RNA
RNA ribonucleic acid
multiple functions
chemically, RNA is relatively simple
RNA forms a range of stable structures
RNA can perform catalytic functions (ribozymes)
tRNA requirement
at least one strong site and many weaker sites
fold stabilisation
half crucifix structures
what Is DNA?
DNA- deoxyribonucleic acid
serves as the information store
chemically DNA is a relatively simple molecule
DNA can detect its own replication
The DNA double helix is remarkably stable
rRNA
Stabilisation of fold and association with 30S 50S and 70S subunits
mRNA
attachment to ribosomes
ribozymes
Mg2+ acts to bind the RNA enzyme to the RNA enzyme to the RNA substrate
DNA
Crucifix structures
DNA/ RNA
polymerase
magnesium is required as
requires of various polynucleotides
kinases
the reversible phosphorylation of protein , resulting in a conformational change in that protein provides a useful control mechanism that allows for the activity of an enzyme to be modulated
what’s under this control mechanism
many proteins are under this controlled mechanism
what do protein kinases do?
add the phosphate group
phosphorylation takes place in which 3 amino acids
serine threonine or tyrosine
the phosphate is supplied as the Mg-ATP complex
phosphateses
remove the phosphate group
where is the ATP bound
The ATP is bound into the protein via the adenine leaving the phosphate chain exposed , or weakly bound
what does an anion centre on the protein do?
An anion centre on the protein then helps to move the triphosphate into position so it can transfer the terminal phosphate group group to the requisite amino acid
is phosphorylation restricted to a single site?
no it is not restricted to a single site on the protein and the protein may be phosphorylated by more than one kinase this allows convergence of cell signalling pathways
