Exam 5: General Chemistry

Passage Heme is found in several proteins, including hemoglobin in blood and myoglobin in muscle.  It has a four-coordinate iron-bound porphyrin structure where ferrous iron (Fe²⁺) is bound to four nitrogen atoms through coordinate covalent bonds.  The most common heme found in the body is heme b in hemoglobin (Figure 1). Figure 1  Structure of heme b found in hemoglobinAlong with the four nitrogen ligands in the porphyrin structure, His F8 also binds to Fe²⁺ in the axial position, leaving the other axial position available to bind oxygen.  In this setting, iron's atomic d orbitals are no longer degenerate.  The energetic difference between the d orbitals depends on the ligands.In deoxygenated heme, iron sits out of the plane formed by the nitrogen ligands in the porphyrin because its d orbitals make it slightly too large to fit in the porphyrin ring.  However, when O₂ binds to heme, iron's electrons re-arrange themselves.  The d orbitals become smaller, and iron sits within the plane of the nitrogen atoms.When iron is scarce in the body, Zn²⁺ will coordinate to the ligands in the protoporphyrin structure through a nonenzymatic process, forming Zn-protoporphyrin IX (ZPP).  ZPP and protoporphyrin IX (PPIX) have distinct emission spectra when excited in the blue range whereas heme does not.  Hematofluorometry can be used as a simple, inexpensive indicator for iron deficiency in whole blood by placing a blood sample in a fluorometer and measuring the amount of ZPP relative to the amount of heme.  Figure 2 illustrates the fluorescence emission spectra for ZPP and protoporphyrin IX measured from a blood sample when ZPP is excited at 425 nm and PPIX is excited at 407 nm. Figure 2  ZPP and PPIX fluorescence emission spectra Adapted from Hennig G, Gruber C, Vogeser M, et al. Dual-wavelength excitation for fluorescence-based quantification of zinc protoporphyrin IX and protoporphyrin IX in whole blood. J Biophotonics. 2014;7(7):514-24. -Which of the following does NOT describe the iron-porphyrin complex formed between Fe²⁺ and the four nitrogen atoms in Figure 1?

Passage Magnetic resonance imaging (MRI) interprets the nuclear relaxation or relaxivity of hydrogen nuclei in resident water molecules.  Hydrogen nuclei in water have two magnetic spin states:  alpha and beta.  In the presence of an applied magnetic field, these spins will align with the field in an "excited" state and then relax back to the "ground" state, producing a signal with intensity proportional to relaxivity.  Frequently, an MRI contrast agent is used to increase the relaxation time in coordinated molecules, resulting in a more intense signal.Commonly used contrast agents include gadolinium-based agents.  Depending on its environment, gadolinium (Gd) can have eight or nine sites in its coordination sphere, allowing Gd³⁺ to interact with eight water molecules as in Gd(H₂O)₈³⁺.  The electronic configuration of gadolinium is shown in Figure 1. Figure 1  Electronic configuration of gadoliniumGd³⁺ alone is toxic to cells because its ionic radius is similar to that of Ca²⁺, allowing Gd³⁺ to displace Ca²⁺ in biologically important settings.  Therefore, Gd³⁺ must be coordinated to an organic ligand such as 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to allow it to pass through the body safely.  When chelated, DOTA displaces the water around gadolinium and leaves only one coordination site for a water molecule (Figure 2). Figure 2  Gd-DOTA with a water coordinated to Gd³⁺Zinc ions (Zn²⁺) are required to store insulin and are co-released when insulin is secreted by the pancreas.  To detect zinc ions in the body, researchers have designed a variation of Gd-DOTA called Gd-daa3 with two diaminoacetate (daa) arms that preferentially bind to Zn²⁺ ions (Figure 3).  When Zn²⁺ is absent, these arms coordinate to Gd³⁺ and create a nine-coordinate complex that prohibits water from binding to Gd³⁺.  Binding of diaminoacetate arms to Zn²⁺ frees Gd³⁺ to coordinate with water molecules.  This configuration results in increased signal intensity in the parts of the cell where Zn²⁺ is located. Figure 3  Gd-daa3 when Zn²⁺ is present Adapted from Louie A. MRI biosensors: a short primer. J Magn Reson Imaging. 2013;38(3):530-9. -When Gd³⁺ binds to DOTA, Gd³⁺ is acting as a(n):

Passage Kidney stones are a common ailment affecting approximately 10% of adults in the United States.  They form when solutes precipitate out of solution as crystals in the urinary tract, and they can cause severe pain in the side, back, abdomen, and groin.  Individuals who have been previously diagnosed with kidney stones have an increased probability of developing new stones relative to unaffected individuals.  Different measures may help prevent the formation of different kinds of stones, so analysis of the composition of stones that have been passed or removed can aid in preventing recurrence.  Stones can be ground into fine powders, dissolved in a small amount of solvent, and analyzed by infrared (IR) spectroscopy, as shown in Figure 1. Figure 1  Schematic of kidney stone analysis by IR spectroscopyIR analysis of kidney stones from 50 individuals revealed the percentage of stones that contain each component, shown in Table 1 along with solubility data.Table 1  Kidney Stone Composition Parameters Some studies indicate that potassium citrate, taken orally, may prevent the formation of calcium oxalate crystals, the most abundant component of kidney stones.  Oxalic acid, shown in Figure 2, is significantly more soluble than calcium oxalate. Figure 2  Structure of oxalic acid and its associated anions with increasing pHPotassium citrate alkalinizes the urine, potentially causing a decrease in oxalate solubility and the formation of more crystals.  However, potassium citrate can also react with calcium oxalate according to the unbalanced equation shown in Reaction 1:CaC₂O₄ + K₃(C₆H₅O₇) → Ca₃(C₆H₅O₇)₂ + K₂C₂O₄Reaction 1Calcium citrate and potassium oxalate are both hundreds of times more soluble than calcium oxalate, so the presence of citrate and potassium ions can help maintain calcium and oxalate ions in solution.  This effect may be sufficient to overcome the decreased solubility that occurs at higher pH levels. Adapted from Primiano A, Persichilli S, Gambaro G, et al. FT-IR analysis of urinary stones: a helpful tool for clinician comparison with the chemical spot test. Dis Markers. 2014;2014:176165. -In addition to calcium oxalate stones, researchers might hypothesize that potassium citrate (a weak base) could reduce the risk of uric acid stones for which of the following reasons?

The molecular structure of a sample of solid, non-ionized L-phosphotyrosine is shown below. What is the net charge of L-phosphotyrosine when placed in an aqueous solution at physiological pH 7.4?  (Note: Assume that the pK_a values of the phosphoryl group are 2.2 and 7.2.)

The figure below shows the titration curve for an acid titrated with aqueous sodium hydroxide. When titrated in solution, which of the following salts would be most likely to produce a similar titration curve?

Passage Hyperbaric oxygenation therapy involves placing a patient in a chamber with oxygen-rich air at greater than atmospheric pressure.  Normal air has approximately 78% N₂, 21% O₂, and trace amounts of other gases.  The pressure within the hyperbaric chamber is typically measured in terms of ATA, or atmospheres absolute (1 ATA is the average atmospheric pressure at sea level, or 1 atm).  A hyperbaric chamber set at 2.5 ATA would be the average atmospheric pressure at sea level (1 ATA) plus the additional pressure applied to the chamber (1.5 ATA).There are two main types of hyperbaric chambers: monoplace chambers and multiplace chambers.  Monoplace chambers accommodate a single person.  The air in these chambers is 100% oxygen and can be raised to a maximum pressure of 3 ATA.  Monoplace chambers are used as therapy for conditions where oxygen supply has been depleted, such as carbon monoxide poisoning.  They are also used when a higher concentration of oxygen in plasma is needed, such as in wound healing.Multiplace chambers are large enough to house at least four people.  The air in these chambers is typically a mixture of oxygen and nitrogen, but the patient breathes pure oxygen through a mask.  Some multiplace chambers can endure maximum pressures of 6 ATA and are typically used to eliminate intravascular air bubbles that can occur from decompression sickness or embolisms.  The high pressure from the multiplace chamber results in a decrease in volume of any air pockets within the body, including the sinuses, inner ear, and unwanted air bubbles in the arteries or veins.Patients report that their ears "pop" during the pressurization process, similar to being on an airplane in flight.  In addition, they report that although there is an initial sense of temperature increasing, the chamber's temperature stays relatively stable during both the pressurization and the depressurization processes. -What is the partial pressure of O₂ in a 3-ATA multiplace chamber filled with 80% O₂ and 20% N₂?

Passage An automated external defibrillator (AED) is a medical device used to send an electric shock to the heart after cardiac arrest.  A key component of the AED is the power source, or battery.  Batteries used in AEDs need to have a good charge-to-weight ratio; they must be safe and reliable as well as rechargeable.Two types of rechargeable batteries used in early models of AEDs are the lead storage (also called lead-acid) battery and the nickel-cadmium (NiCd) battery.  These batteries consist of multiple electrochemical cells that are connected in series to deliver a potential between 9 V and 18 V.  A capacitor allows the AED to accumulate charge so that it can deliver between 300 V and 1,000 V.Some AEDs use a sealed lead storage battery.  Lead storage batteries are robust and hold a charge for a long time.  However, they have a low energy-to-weight ratio.  Each lead storage cell delivers approximately 2.0 V, and a battery of four cells weighing 1000 g can provide 30 W∙h of energy. Figure 1  Electron flow in a lead storage battery when discharging and chargingThe half reactions for the anode and cathode of a lead storage battery in 4 M of sulfuric acid (H₂SO₄) are shown in Reactions 1 and 2: Reaction 1 Reaction 2 NiCd batteries have a higher energy-to-weight ratio than lead storage batteries but cannot hold as much charge.  Each NiCd cell delivers approximately 1.3 V, and a single-cell battery weighing 120 g can provide 7.2 W∙h of energy.The half reactions at the anode and cathode for a NiCd battery in KOH are shown in Reactions 3 and 4: Reaction 3 Reaction 4 -Would the concentration of H₂SO₄ remain constant as a lead storage battery is discharged?

Which of the following statement(s) is (are) consistent with the molar mass of ammonium carbonate?1.00 mol of (NH₄)₂CO₃ contains 96.11 g of mass.96.11 g of (NH₄)₂CO₃ contains 6.022 × 10²³ (NH₄)₂CO₃ molecules.96.11 amu of (NH₄)₂CO₃ contains 1.00 mol (NH₄)₂CO₃.

A Galileo thermometer consists of a cylinder filled with a known solution and several sealed glass bulbs partially filled with water.  Each bulb effectively acts as an isolated system.  If one of the bulbs has the same density as the solution at 25 °C, how will its position and the density of the solution change as the temperature of the solution decreases from 25 °C to 20 °C?

Passage The radiopharmaceutical 2-deoxy-2-(¹⁸F)fluoro-D-glucose (abbreviated as ¹⁸F-FDG) is a modified form of D-glucose in which the hydroxyl group on the 2-carbon of the molecule has been replaced with a positron-emitting ¹⁸F radionuclide.  Synthesis of ¹⁸F-FDG is accomplished in several steps involving both nuclear and chemical reactions, as shown in Figure 1. Figure 1  Synthetic scheme for 2-deoxy-2-(¹⁸F)fluoro-D-glucoseInitially, a target of ¹⁸O-enriched water (¹⁸OH₂) is bombarded by protons using a cyclotron to achieve a (p-n) nuclear reaction in which a proton hitting the ¹⁸O nucleus is absorbed by the nucleus, causing the ejection of a neutron and forming an ¹⁸F nucleus.  Following separation of the resulting ¹⁸F⁻ anions from the residual ¹⁸OH₂ via an ion exchange column, ¹⁸F⁻ is used in a nucleophilic substitution reaction with an acetylated mannose triflate substrate.  Subsequent hydrolysis to remove the acetyl protecting groups yields ¹⁸F-FDG.Because ¹⁸F-FDG is an analog of D-glucose, it is readily taken into cells by the same metabolic processes as D-glucose.  Once inside the cells, the positron emissions of the ¹⁸F radionuclide can be detected by positron emission tomography (PET) scans to produce diagnostic medical images of objects such as tumors.  Emissions from the ¹⁸F radionuclide subsequently diminish over time via radioactive decay (Figure 2). Figure 2  Nuclear decay of the ¹⁸F radionuclideBecause of limitations in the spatial resolution of PET scanners, when an object (such as a tumor) is smaller than 30 mm in diameter, the measured specific uptake value (SUV) of ¹⁸F-FDG accumulated within the object is lower than the actual SUV.  The recovery coefficient (the ratio of the measured SUV to the actual SUV) shows that the measured SUV decreases as the size of the object decreases below the 30-mm threshold (Figure 3). Figure 3  Recovery coefficient as a function of object size in a PET scan with a spatial resolution of 7 mm using ordered subsets expectation maximization (OSEM) image processing Adapted from: S. Yu. "Review of F-FDG Synthesis and Quality Control." Biomed Imaging Interv J. ©2006 Department of Biomedical Imaging, Faculty of Medicine, University of Malaysa; and P. E. Kinahan, et al., "Positron emission tomography-computed tomography standardized uptake values in clinical practice and assessing response to therapy." Semin Ultrasound CT MR. ©2010 Elsevier. -The last step in the synthesis of ¹⁸F-FDG is a hydrolysis reaction to remove the acetyl (OAc) protecting groups.  If 524 mg of acetylated ¹⁸F-FDG is hydrolyzed, how many millimoles of the acetyl group are removed in the reaction?  (Note: The molar mass of the acetylated ¹⁸F-FDG is 349.31 g/mol = 349.31 mg/mmol.)

Passage Although acetylsalicylic acid (aspirin) is a well-known and widely used analgesic and anti-inflammatory agent, copper(II) acetylsalicylate, a copper complex formed from aspirin and copper, has also been found to exhibit some distinctive and potentially beneficial pharmacological properties.  Formation of copper(II) acetylsalicylate is achieved when the conjugate base of aspirin, acetylsalicylate (C₉H₇O₄⁻), binds to Cu²⁺ ions in solution, as outlined in Reaction 1.4 NaC₉H₇O₄(aq) + 2 CuSO₄(aq) → Cu₂(C₉H₇O₄)₄(s) + 2 Na₂SO₄(aq)Reaction 1Using Reaction 1, a researcher synthesized a sample of copper(II) acetylsalicylate for analysis.  A small volume of 0.50 M aqueous copper(II) sulfate (molar mass = 159.6) was mixed into 100 mL of filtered, saturated aqueous sodium acetylsalicylate (molar mass = 202.2) at room temperature and slowly stirred.  Formation of copper(II) acetylsalicylate (molar mass = 843.7) was immediately observed as a bright blue precipitate.  The precipitate was then isolated by filtration and dried, affording the product complex in high yield. Adapted from: Seguel GV, Rivas BL, Contreras JG. Synthesis and characterization of copper complexes: interaction of metalliccarboxylates with 1,3-thiazole ligand. Journal of the Chilean Chemical Society. 1970; 58(4):1967. -In the reaction, just prior to precipitation, what is the ratio of the concentration of copper(II) acetylsalicylate to the concentration of sodium sulfate?

Passage A group of students were given water from two reservoirs and asked to determine water hardness using flame atomic absorbance (AA) spectroscopy.  Water hardness can be found by relating the concentration of calcium and magnesium ions to the concentration of carbonate species in the sample using Equation 1.[CO₃^2-] = 2.5[Ca²⁺] + 4.1[Mg²⁺]Equation 1To correlate the concentration of the metal ions to absorbance, the students made standard solutions of MgO (MW = 40.31 g/mol) and CaO (MW = 56.08 g/mol) by diluting small portions of 0.01 M MgO and 0.01 M CaO stock solutions with 2% HNO₃ into 100 mL volumetric flasks.  The calibration curves generated from the standard solutions are shown in Figures 1 and 2. Figure 1  Calibration curve from the absorption of the Ca²⁺ solution standards Figure 2  Calibration curve from the absorption of the Mg²⁺ solution standardsLanthanum(III) chloride (MM = 245.25) can be used to eliminate chemical interference in a sample by competitively binding to PO₄³⁻, releasing calcium to be atomized in the flame for detection.The students prepared unknown Samples 1 and 2 by mixing 25 mL reservoir water, 16 mL of 2% HNO₃, and 9 mL of 0.1 M LaCl₃ for a total sample volume of 50 mL each.  The samples were each tested three times using flame AA spectroscopy, yielding the results reported in Table 1.Table 1  AA Spectroscopy Results for Reservoir Water Samples -Based on the information in the passage, what is the mass of calcium (MW = 40.1 g/mol) in Sample 1 after dilution?

Passage Nuclear medicine uses radiopharmaceuticals for disease treatment and as tracers in medical imaging studies.  Yttrium-90 (⁹⁰Y) is a radiopharmaceutical agent used to treat overgrown joint lining known as pigmented villonodular synovitis, as well as some forms of liver cancer.  It has a half-life of about 64 hours.Although the relatively short half-life of ⁹⁰Y is optimal for use in medical applications, transportation and storage of the radiopharmaceutical are not feasible.  As a result, strontium-90 (⁹⁰Sr), with a half-life of 28.8 years, is the most common source of ⁹⁰Y.  ⁹⁰Sr is created by a nuclear fission process that begins with uranium-235 (²³⁵U) in a nuclear reactor as shown in Reaction 1.²³⁵U → ⁹⁰Sr + ZReaction 1Fission of ²³⁵U produces ⁹⁰Sr as well as additional fission products (Z) including, but not limited to, technetium-99 (⁹⁹Tc), iodine-129 (¹²⁹I), and zirconium-93 (⁹³Zr).  Figure 1 shows the distribution of fission products. Figure 1  Distribution of ²³⁵U fission products by atomic weightTo create the final ⁹⁰Y required for nuclear medicine studies, ⁹⁰Sr decay is carried out in a controlled ⁹⁰Y generator.  ⁹⁰Y is then separated from residual ⁹⁰Sr for use in clinical applications. Adapted from Wheeler CE. Comments on vaccines, August 1987. J Am Acad Dermatol. 1988;18(1 Pt 2):232-4. -A patient is injected with 20 ng of ⁹⁰Y.  Assuming yttrium is not excreted, how long will it take for the initial amount of ⁹⁰Y to be reduced to 2.5 ng?

Consider the equilibrium that exists for a saturated aqueous solution of PbCl₂. Which expression gives the solubility product constant K_sp for PbCl₂ if the [Pb²⁺] = n mol/L?

Passage Umami is one of five basic tastes that humans recognize, and it is triggered by L-amino acids as well as some synthetic ingredients and organic acids.  Three common umami tastant molecules are shown in Figure 1. Figure 1  Three common tastant molecules known to trigger the umami taste sensationUmami taste signals are triggered upon binding of tastant molecules to the G protein-coupled receptor (GPCR) heterodimer T1R1-T1R3, which ultimately causes the breakdown of phosphatidylinositol 4,5-bisphosphate (PIP₂) into the messenger molecules inositol-1,4,5-trisphosphate (IP₃) and diacylglycerol (DAG).  IP₃ triggers the release of Ca²⁺ cations and the subsequent gating of the taste-transduction channels (Figure 2). Figure 2  Signal pathway for transduction of umami taste sensationInosine monophosphate (IMP) has been suggested as enhancing (potentiating) the response of T1R1+T1R3 GPCRs to umami tastant molecules.  Scientists tested this hypothesis by culturing receptors from human embryonic kidney (HEK) cells containing promiscuous G proteins.  The HEK cells were then stimulated with umami tastants in the presence or absence of IMP.  In each test, the cells were exposed to the same amounts of amino acid tastant and IMP.  The number of cells that responded to each tastant was measured using a calcium indicator dye (FURA-2AM) in conjunction with fluorescence microscopy.  By comparing the cellular response ratio of the stimulated to unstimulated HEK cells, the extent of potentiation can be assessed.  The results are shown in Figure 3. Figure 3  Quantification of amino-acid responses for T1R1+T1R3 with and without IMP Adapted from Nelson G, Chandrashekar J, Hoon MA, et al. An amino-acid taste receptor. Nature. 2002;416(6877):199-202. -Which of the following statements is true regarding the bonds in the tastant molecule L-methionine?The pi bond in C=O has a smaller dissociation energy than the sigma bond.The C=O bond is stronger than the C-O bond.The pi bond in C=O is more stable than the sigma bond.

What is the mass percent of alcohol in a solution containing 62 mL of ethyl alcohol mixed into 200 mL of water?  (Note: Density of ethyl alcohol = 0.8 g/mL; density of water = 1 g/mL.)

Under anaerobic conditions, hemoglobin (HbFe²⁺) can react with nitrite to form methemoglobin (HbFe³⁺).HbFe²⁺ + NO₂⁻ + 2H⁺ → HbFe³⁺ + NO + H₂OWhich element is reduced in the reaction?

Passage The alkaline-earth metals are a highly reactive family of metals occupying Group 2 (IIA) of the periodic table.  In their elemental form, the alkaline-earth metals have a shiny, silvery-white to slightly yellowish appearance.  The alkaline-earth metals exhibit some similarities to the chemistry of the alkali metals (Group 1) but are a little less reactive.Atoms of the alkaline-earth metals (M) have only two valence electrons and a low first and second ionization energy.  Consequently, these metals readily lose both electrons to produce cations with a +2 charge (M⁺²) during reactions with nonmetals.  As a result, the alkaline-earth metals do not exist in their elemental metallic form in nature.  Instead, the Group 2 elements are found primarily as metal oxides, which form by reacting oxygen (Reaction 1). Similarly, elemental samples of alkaline-earth metals will react with elemental halogens (X₂) to form metal halides (Reaction 2), all of which are ionic except for BeCl₂. Except for beryllium, the alkaline-earth metals react with water to produce very basic metal hydroxide solutions and hydrogen gas (Reaction 3). The most difficult alkaline-earth metal to study is radium, because it is a rare radioactive element that is produced from the nuclear decay of uranium.  The most common natural isotope, radium-226, has a half-life of 1,600 years and decays by alpha emission into radon-222 (Reaction 4). -Which of the following alkaline-earth species are diamagnetic?  (Note: Assume that the species are single, isolated units that are not part of a bulk metal sample.)CaCa⁺²Sr

Which of the following compounds has a boiling point that is more than 30 °C higher than that of 1,3-propanediol, HOCH₂CH₂CH₂OH?

Passage Kidney stones are a common ailment affecting approximately 10% of adults in the United States.  They form when solutes precipitate out of solution as crystals in the urinary tract, and they can cause severe pain in the side, back, abdomen, and groin.  Individuals who have been previously diagnosed with kidney stones have an increased probability of developing new stones relative to unaffected individuals.  Different measures may help prevent the formation of different kinds of stones, so analysis of the composition of stones that have been passed or removed can aid in preventing recurrence.  Stones can be ground into fine powders, dissolved in a small amount of solvent, and analyzed by infrared (IR) spectroscopy, as shown in Figure 1. Figure 1  Schematic of kidney stone analysis by IR spectroscopyIR analysis of kidney stones from 50 individuals revealed the percentage of stones that contain each component, shown in Table 1 along with solubility data.Table 1  Kidney Stone Composition Parameters Some studies indicate that potassium citrate, taken orally, may prevent the formation of calcium oxalate crystals, the most abundant component of kidney stones.  Oxalic acid, shown in Figure 2, is significantly more soluble than calcium oxalate. Figure 2  Structure of oxalic acid and its associated anions with increasing pHPotassium citrate alkalinizes the urine, potentially causing a decrease in oxalate solubility and the formation of more crystals.  However, potassium citrate can also react with calcium oxalate according to the unbalanced equation shown in Reaction 1:CaC₂O₄ + K₃(C₆H₅O₇) → Ca₃(C₆H₅O₇)₂ + K₂C₂O₄Reaction 1Calcium citrate and potassium oxalate are both hundreds of times more soluble than calcium oxalate, so the presence of citrate and potassium ions can help maintain calcium and oxalate ions in solution.  This effect may be sufficient to overcome the decreased solubility that occurs at higher pH levels. Adapted from Primiano A, Persichilli S, Gambaro G, et al. FT-IR analysis of urinary stones: a helpful tool for clinician comparison with the chemical spot test. Dis Markers. 2014;2014:176165. -At which pH would oxalate adopt the greatest net dipole moment?