CHM1022 Week 12 Lecture Notes - Bioinorganic Chemistry PDF

Week 12/Lecture 1: Bioinorganic chemistry Weekly objectives 1. Describe the importance of transition metals in biological processes and medicine 2. Apply knowledge of ligands from previous weeks to biological molecules 3. Explain the basic principles behind biological oxygen carriers (haemoglobin,...

Week 12/Lecture 1: Bioinorganic chemistry Weekly objectives 1. Describe the importance of transition metals in biological processes and medicine 2. Apply knowledge of ligands from previous weeks to biological molecules 3. Explain the basic principles behind biological oxygen carriers (haemoglobin, myoglobin, haemocyanin) 4. Apply knowledge of d-orbital splitting and electron configuration from previous weeks to analyse the function of biological systems Week 12: Biological Molecules as Ligands Biological Ligands Recap from pre-workshop material From the pre-workshop activity:  Groups ACTIVITY 1: Biological Molecules as Ligands 5 mins Question 1 Using the pre-workshop activity as a guide to your understanding, identify which of the amino acids are ligands to transition metals. ACTIVITY 1: Discussion and Feedback From the pre-workshop activity, you should have noted that amino acids with an oxygen in their side- chain could potentially act as ligands. This also extends to other atoms that have lone pairs available, such as nitrogen or sulfur.  Groups ACTIVITY 1: Ligands with Biological Molecules Question 2 Identify and explain which of the ligands (or a couple) would rank highest in the spectrochemical series. 5 mins ACTIVITY 1: Discussion and Feedback The groups containing OH are weaker field ligands than those containing NH3 so the residues arginine and histidine may rank the highest due to the larger NH content at the R-group. Week 12:Oxygen Carriers Oxygen Carriers: Myoglobin and Haemoglobin What is Haemoglobin? Myoglobin Haemoglobin Showing the Fe porphyrin group ⍺2 β2 tetramer with four haem Fe groups in yellow located between the helices E and F The ⍺ and β subunits are very similar to myoglobin Recap from pre-workshop material ChewmTube3D: https://www.chemtube3d.com/bc-26-16-2/ Recap from pre-workshop material ACTIVITY 1: from pre-workshop material Draw the d-orbital splitting diagram for Fe in oxy-Mb and identify whether it is high or low spin state. Fe3+ has an electron configuration of [Ar]3d5. So we have 5 d-electrons to consider. From the images provided of oxy-Mb, we know that the structure is octahedral. With so many N-bound ligands, the gap between the lower orbitals and the higher orbitals is large. That results in the low spin, with only 1 unpaired electron – Fe3+ is low spin in oxy-Mb. ACTIVITY 2: from pre-workshop material Considering the IR stretching frequency of O2 in oxy-Mb is ~1107 cm-1 what is the most likely nature of O2 if the following IR data is known? IR data (cm-1) Neutral oxygen (O2) 1560 Superoxide (O2-) 1140 Peroxide (O22-) 800 ACTIVITY 2: Discussion and feedback Considering the IR stretching frequency of O2 in oxy-Mb is ~1107 cm-1 what is the most likely nature of O2 if the following IR data is known? IR data (cm-1) Neutral oxygen (O2) 1560 Superoxide (O2-) 1140 Peroxide (O22-) 800 Once you identify the most likely nature of O2 in oxy-Mb determine the number of unpaired electrons in this molecule of O2 1107 cm-1 is closest to 1140 cm-1. So the oxygen in oxy-Mb must be a super oxide (O2-). The superoxide has one unpaired electron.  Groups ACTIVITY 3: Properties of Myoglobin Question 1 Why is the oxymyoglobin (oxy-Mb) complex diamagnetic? Explain your response. 10 mins Consider that both Fe and O2 in this complex (oxy-Mb) have one unpaired electron each. ACTIVITY 3: Discussion and Feedback Recall that the low spin state of the Fe3+ has one unpaired electron and that the superoxide state also has one unpaired electron. The unpaired electron in this superoxide can couple with the unpaired electron from the Fe3+ - resulting in an overall diamagnetic compound with no unpaired electrons. eg O2 FeIII t2g d5 low spin Antiferromagnetic coupling => overall diamagnetic complex ACTIVITY 3: Discussion and Feedback When atoms or molecules with unpaired electrons are close enough, their magnetic spins can display magnetic coupling, whereby their spins try to orientate in either the same direction (ferromagnetic coupling) or in opposite directions (antiferromagnetic coupling). If the atoms or molecules are too far apart, it is just a simple paramagnet. Ferromagnetic coupling Paramagnet Spins try to orientate in the same Random orientation of Antiferromagnetic coupling direction. Long range in this spins (in absence of Spins try to orientate in opposite example (Fe magnet). magnetic field). Metals directions and cancel each other too far apart to couple. out. Short range in this example. Oxygen Carriers: Haemocyanin Haemocyanins – Cu metalloprotein Haemocyanins are O2 carrying copper-containing proteins Found in molluscs and anthropods Crabs, snails, scorpions, spiders Blue blood from Cu(II) binding to O2 Horseshoe crab: “Super blue blood” $15,000 a litre Super antibacterial properties Special clotting agent that stops infection http://www.youtube.com/watch?v=e8KlAmtIu1E Horseshoe crab  ACTIVITY 2: Discussion and Feedback Let’s now consider the haemocyanin oxygen transfer system. Active site – oxygenated Active site – deoxygenated Oxyhaemocyanin Deoxyhaemocyanin Before oxygen binding After oxygen binding occurs, occurs, copper is in the +1 copper is in the +2 oxidation state oxidation state tetrahedral square pyramidal ChewmTube3D: https://www.chemtube3d.com/bc-26-20/ ACTIVITY 2: Discussion and Feedback But … haemocyanin is diamagnetic, implying no lone electrons! IR results show that the oxygen is now in the peroxide form, so this is not the source of this effect. In this case, the spins on the copper atoms couple antiferromagnetically across the peroxide bridge, and cancel each other out. Cu(II) [O2]2- Cu(II) Week 12/Lecture 2: Metals in Medicine Platinum in Medicine Platinum in Medicine O O O O H 3N Cl O O Pt Pt O O H 2N NH2 H 3N Cl Pt Cis-platin H 3N NH3 Carboplatin Oxaliplatin 1978 1989 2002 Pt(II) Pt(IV) O O H 3N Cl N Pt Cl Currently H2 in trials O O Satraplatin Cisplatin: Mode of action  Individual ACTIVITY 1: Binding to DNA For which of the following single-stranded DNA molecules would cis-platin most likely bind? Explain your choice. a) AGTCC 5 mins. b) GAGTT c) TGGAC d) CGATG NH2 O NH2 O N N N NH N NH N N N N NH2 N O N O sugar sugar sugar sugar Adenine (A) Guanine (G) Cytosine (C) Thymine (T) ACTIVITY 1: Discussion and Feedback Answer: C. TGGAC Cis-platin prefers the purine base pairs A and G over the pyrimidine bases C and T, but also prefers guanine over adenine as guanine can form a stronger bond with cis-platin. https://www.chemtube3d.com/bc-27-3/ Chromium as a diagnostic Chromium 51 is used for the labeling of red blood cells for the evaluation of mass or volume, survival time and sequestration studies, and for the diagnosis of gastrointestinal bleeding. ACTIVITY 2: Biologically-active Chromium Coordination Complexes Question 1: What role do Cr3+ and the ligand(s) have in the biological properties of each of these coordination complexes? Hint : Week 8 Chromium in diet pills  ACTIVITY 2: Discussion and feedback Answers: Ethylenediaminetetraacetate [51Cr]chromium(III) is a radioactive compound used to evaluate kidney function by measuring the rate of clearance from the body. The role of the edta ligand is to ensure that 51Cr is non- bioavailable. The complex is hydrophilic and very stable, which enables it to be filtered from the blood and through the kidneys intact. Tris(picolinate)chromium(III) is sold as a nutritional supplement for chromium deficiencies. The role of the picolinate ligands is to provide bioavailable Cr3+. The Aspartic acid complex is neutral, lipophilic and relatively stable, which enables it to absorb into the tissues, metabolise and release Cr3+ to amino acids such as aspartic acid and glutamic acid Glutamic acid Summary Today we have: Described the importance of transition metals in biological processes and medicine Applied knowledge of ligands from previous weeks to biological molecules (eg. amino acids, nucleotides) Explained the basic principles behind oxygen carriers (haemoglobin, myoglobin, haemocyanin) Applied knowledge of d-orbital splitting and electron configuration from previous weeks to analyse the function of biological systems