Intro to Phosphate Anhydrides - Online Tutor, Practice Problems & Exam Prep

Phosphate anhydrides consist of two or more phosphate groups linked together, with pyrophosphoric acid being the simplest form. Formed through a condensation reaction of phosphoric acid, they play a crucial role in biological systems, particularly in ATP (Adenosine Triphosphate) and ADP (Adenosine Diphosphate). Alkylated phosphate anhydrides undergo nucleophilic attack, leading to carbon-oxygen bond cleavage, producing pyrophosphate ions and alkylated nucleophiles. This reaction can be reversible but becomes irreversible with enzyme-catalyzed nucleophilic acyl substitution, emphasizing the dynamic nature of these biochemical processes.

Intro to Phosphate Anhydrides Concept 1

Hey everyone, so let's talk about a Phosphate Anhydride. Now, we're going to say a Phosphate Anhydride consists of 2 or more phosphate groups linked together. We're going to say the simplest neutral form is our pyrophosphoric acid, and it's formed by the condensation reaction between 2 phosphoric acid molecules. So if we come here and take a look, we have 2 phosphoric acid molecules. We're using H⁺ catalyst in order to initiate this condensation reaction.

Remember, in a condensation reaction, we're just essentially losing water. So let's say we lose water this way. What happens is we lose water so those 2 separate molecules come together, join together to create our one new molecule. Here, we'd still have our OH groups. This is its acidic form so the OH groups, they're protonated.

This would represent our pyrophosphoric acid. And here, this would be a phosphate anhydride. Remember, an anhydride, we learned about it being a carbonyl connected to oxygen connected to another carbonyl. So this is a typical anhydride. We're dealing with a phosphate anhydride now.

So we have phosphorus coming in and being substituted in. Now, here we're going to say the slightly basic environment of biological systems makes the pyrophosphate predominant. So here instead of having our OH's protonated, they're deprotonated because our biological systems are slightly basic around 7.4, so we'd have all negative oxygens. This would be our pyrophosphate. Now, we've actually been dealing with our phosphate anhydrase for quite a while if you've taken biology and other science courses.

We know about ATP, which is Adenosine Triphosphate. It has a portion of it which is a phosphate anhydride. It was there the whole time. Now, here we would say with our ATP which is Adenosine Triphosphate, so ATP, We'd have these negative oxygens because again, the basic environment that they exist in. And then we'd have our 5-membered ring.

We'd have it as a ribosugar. And then we have our nitrogenous base here in terms of adenine or adenine. Right? So again, we know what a phosphate anhydride is now, how it's created, and remember, ATP is the most important, most common type of phosphate anhydride. Followed by ADP, which is Adenosine diphosphate where we've lost one of these phosphate groups and now we only have 2.

Right? So ATP is the most important followed by ADP. And so keep that in mind when we continue our exploration and discussion of phosphate anhydrides.

Intro to Phosphate Anhydrides Concept 2

Now, we know what a phosphate anhydride is. It's the phosphorus version of a typical anhydride. But now let's take a look at an alkylated phosphate anhydride. We're going to say alkylated phosphate anhydrides undergo nucleophilic attack that leads to carbon-oxygen bond cleavage. Now, the nucleophile attacks the alpha carbon giving products via a reversible acid mechanism.

And we're going to say, at the end, what we're going to have is a pyrophosphate ion and an alkylated nucleophile. And we take a look here, we have our alkylated phosphate anhydride. Remember, this represents our phosphate anhydride. It's alkylated because there's an alkyl group attached to it. Now we're going to say that the point of connection between our carbon and that oxygen, this represents our alpha carbon.

This would be beta. Now, our nucleophile comes in and it attacks the alpha carbon and this causes this bond to break and go to the oxygen. So at the end, what we would have is our pyrophosphate ion. So we won't worry about lone pairs here, but we know they're there. So here goes our pyrophosphate, and then we have our alkylated nucleophile.

So here's the Ethyl and it's connected to the Nucleophile that attacked the Alpha Carbon. Alright. So this will represent our 2 products and again this is the Alpha Carbon. This reaction is reversible which would mean that this pyrophosphate itself could also act as a nucleophile if it wanted and hit this alpha carbon, kicking out the nucleophile and recreating our initial reactants. Now, the overall process though can be made irreversible upon enzyme catalyzed nucleophilic acyl substitution of the pyrophosphate ion.

So right now, it could be reversible, but once we start playing around with this pyrophosphate through a NAS mechanism, that makes the overall process irreversible because if we start attacking this pyrophosphate, it's not around to do a nucleophilic attack of this alpha carbon and recreating our initial reactants. Alright. So just keep that in mind when we're talking about these phosphate anhydrides and how they can operate with a nucleophile attacking the alpha carbon.

Intro to Phosphate Anhydrides Example 1

In this example question, it says, provide the mechanism for the reversible nucleophilic attack of propyl diphosphate with the iodide ion. Alright. So diphosphate. So we have here our diphosphate, and it's connected to a propyl. And they're telling us we're going to attack it with an iodide.

Now remember, this nucleophile will attack the alpha carbon, which is this carbon right here. So it comes in, hits this alpha carbon causing this bond to break and go to the oxygen. So what we're going to create is our pyrophosphate ion plus our alkylated nucleophile. So here we create our 1-iodopropane. So this would be our products that formed within this given reaction.

It's reversible. We have our reversible arrows. So this would be the overall answer.

Using methylcyclohexane as a starting material, predict the final product based on the list of reagents given?

• A.
• B.
• C.
• D.

Beginning from propane, determine the chemical steps needed to prepare the following compound. 

• A. 1. Br₂/hv2. NaNH₂ 3. BH₃ • THF4. H₂O₂, NaOH5. SOCl₂ 6. Triphosphate
• B. 1. Br₂/hv2. NaNH₂ 3. H₃O⁺4. SOCl₂ 5. NH₃ 6. Triphosphate
• C. 1. BH₃ • THF2. H₂O₂, NaOH 3. SOCl₂4. Triphosphate
• D. 1. HBr2. Triphosphate3. SOCl₂

Here’s what students ask on this topic:

What is a phosphate anhydride and how is it formed?

A phosphate anhydride consists of two or more phosphate groups linked together. The simplest form is pyrophosphoric acid, which is formed through a condensation reaction between two phosphoric acid molecules. In this reaction, a water molecule is lost, allowing the two phosphoric acid molecules to join together. The reaction can be catalyzed by an H⁺ ion. In biological systems, the slightly basic environment (pH ~7.4) leads to the deprotonation of the OH groups, resulting in pyrophosphate ions.

What role do phosphate anhydrides play in biological systems?

Phosphate anhydrides play a crucial role in biological systems, particularly in energy transfer. The most important phosphate anhydride is ATP (Adenosine Triphosphate), which stores and transfers energy within cells. ATP consists of three phosphate groups linked together, and its hydrolysis releases energy that is used for various cellular processes. ADP (Adenosine Diphosphate) is another important molecule, formed by the loss of one phosphate group from ATP. These molecules are essential for metabolism and other biochemical reactions.

How do alkylated phosphate anhydrides undergo nucleophilic attack?

Alkylated phosphate anhydrides undergo nucleophilic attack at the alpha carbon, leading to carbon-oxygen bond cleavage. The nucleophile attacks the alpha carbon, causing the bond between the carbon and oxygen to break, resulting in the formation of a pyrophosphate ion and an alkylated nucleophile. This reaction is initially reversible, but it can become irreversible through enzyme-catalyzed nucleophilic acyl substitution of the pyrophosphate ion, preventing the reformation of the initial reactants.

What is the difference between ATP and ADP in terms of phosphate anhydrides?

ATP (Adenosine Triphosphate) and ADP (Adenosine Diphosphate) are both phosphate anhydrides, but they differ in the number of phosphate groups. ATP contains three phosphate groups linked together, while ADP contains two. The conversion of ATP to ADP involves the loss of one phosphate group, releasing energy that is used for various cellular processes. This energy transfer is essential for metabolism, muscle contraction, and other biochemical reactions.

What is the significance of pyrophosphate ions in biochemical reactions?

Pyrophosphate ions play a significant role in biochemical reactions, particularly in energy metabolism and nucleic acid synthesis. They are formed during the hydrolysis of ATP and other nucleotide triphosphates. Pyrophosphate ions can act as nucleophiles in various reactions, and their hydrolysis to inorganic phosphate provides a thermodynamic driving force for many biochemical processes. This hydrolysis is often catalyzed by enzymes, making the reactions irreversible and ensuring the proper flow of metabolic pathways.