Fact-checked by Grok 2 weeks ago

Phosphoryl group

The phosphoryl group, generally represented as >P=O (where > denotes two attachments) or as -PO₃²⁻ in its dianionic form, is a functional group consisting of a central phosphorus atom bonded to an oxygen atom with partial double-bond character due to resonance, and typically two or three other substituents.^[1] In chemistry, it appears in compounds such as phosphoryl chloride (POCl₃), used in organic synthesis, while in biological systems, it is central to phosphoryl-transfer reactions, where the -PO₃²⁻ unit is transferred from a donor molecule (such as ATP) to an acceptor, facilitating energy or chemical information transfer.^[2] These reactions often proceed with inversion of configuration at the phosphorus atom and may be coordinated by divalent metal ions like Mg²⁺.^[1] The phosphoryl group is derived from phosphoric acid (H₃PO₄) and forms part of phosphate esters, anhydrides, and nucleotides.^[3] Its bonds, especially in phosphoanhydrides, are high-energy due to electrostatic repulsion and the stability of hydrolysis products. Thousands of enzymes, including kinases and phosphatases, catalyze these transfers, playing key roles in bioenergetics (e.g., ATP hydrolysis releasing approximately 30.5 kJ/mol under standard conditions), signal transduction via protein phosphorylation, and nucleic acid structure.^[1] Dysregulation of these processes is linked to diseases like cancer.^[2] The phosphoryl group's versatility underscores its importance in both chemical synthesis and life's processes.^[1]

Definition and Nomenclature

Core Definition

The phosphoryl group is a trivalent functional group denoted as >P(=O)−, consisting of a phosphorus atom bonded to three other atoms or groups via single bonds and featuring a characteristic phosphorus-oxygen double bond.^[4] This group serves as a key structural motif in organophosphorus compounds, where the phosphorus acts as the central atom with a formal positive charge and the oxygen in the P=O bond bearing a partial negative charge.^[5] Common representations include (RO)₃P=O for trialkoxy derivatives, where R denotes alkyl groups, and (RO)₂P(O)Cl for phosphoryl chlorides, illustrating the group's versatility in substitution patterns.^[5] The phosphoryl group is derived from phosphoric acid (H₃PO₄), a triprotic acid, through the replacement of one or more hydroxyl hydrogens by other substituents, thereby highlighting the central phosphorus atom's tetrahedral coordination to oxygen atoms.^[5] The term "phosphoryl" originates from "phosphorus" combined with the suffix "-yl," a nomenclature convention denoting a monovalent radical or functional group in organic chemistry.^[4] It is distinct from the related phosphate ion (PO₄³⁻), a fully deprotonated polyatomic anion.^[6]

Nomenclature Conventions

The nomenclature of compounds containing the phosphoryl group adheres to the substitutive nomenclature rules outlined in the IUPAC Recommendations for organic phosphorus compounds. The prefix "phosphoryl-" denotes the trivalent >P(=O)− unit, where phosphorus is bonded to a double-bonded oxygen and two or three other substituents.^[7] Simple phosphoryl halides exemplify this convention: phosphorus oxychloride (POCl₃) is systematically named phosphoryl trichloride, while phosphoryl fluoride (POF₃) is phosphoryl trifluoride.^[7] More substituted derivatives incorporate alkyl or alkoxy groups, such as dimethyl phosphoryl chloride for (CH₃O)₂P(O)Cl, which is alternatively termed dimethyl phosphorochloridate in preferred IUPAC nomenclature.^[8] Derivatives like phosphoramides, where one or more hydroxy groups of phosphoric acid are replaced by amino substituents (e.g., (RO)₂P(O)NR₂), are named using the suffix "-phosphoramidate" or as substituted phosphoramidic acids; for instance, O,O-diethyl phosphoramidate for (C₂H₅O)₂P(O)NH₂.^[9] Phosphonates, featuring the -P(O)(OH)₂ group attached to carbon, employ the prefix "phosphono-" in substitutive names, such as ethylphosphonic acid for CH₃CH₂P(O)(OH)₂, distinguishing them from oxygen-linked phosphoryl structures.^[7] In biochemical contexts, the infix "phospho-" has largely supplanted "phosphoryl-" for diester linkages since the 1976 recommendations.^[10] The phosphoryl group, denoted as >P(=O)−, represents a unit where phosphorus is formally trivalent, bound to three attachments and featuring a double bond to oxygen, distinguishing it from the phosphate group. The phosphate group, often PO₄³⁻ or more commonly −OPO₃²⁻ in its monoester form, involves pentavalent phosphorus coordinated to four oxygen atoms, typically through an oxygen bridge in organic contexts, and carries a higher degree of ionic character or esterification.^[11] In contrast to the phosphono group, −P(=O)(OH)₂, and the phosphonato group, −P(=O)(O⁻)₂, which are characterized by a direct carbon-phosphorus bond and include explicit hydroxyl or deprotonated oxide ligands respectively, the phosphoryl group lacks these acidic substituents and is generally oxygen-linked. These phosphono and phosphonato functionalities arise from phosphonic acids and their anions, emphasizing P-C connectivity over the P-O linkage prevalent in phosphoryl-containing compounds.^[12] The term "phosphoryl" is used strictly in chemical nomenclature to describe the >P(=O)− unit in trivalent phosphorus derivatives, but in biochemical contexts, it is applied more loosely to the −PO₃ moiety transferred during phosphorylation reactions, such as those involving ATP. This contextual flexibility helps describe energy transfer processes without implying the precise structural details of the inorganic phosphate ion.^[11]

Group	Formula	Key Features
Phosphoryl	>P=O	Trivalent P, double bond to O, three attachments; covalent P-O linkage common.
Phosphate	−O−PO₃²⁻	Pentavalent P, four O ligands, often esterified or ionic; oxygen-bridged.^[11]
Phosphono	−P(=O)(OH)₂	Direct P-C bond, two OH groups; from phosphonic acids.^[12]
Phosphonato	−P(=O)(O⁻)₂	Deprotonated phosphono, direct P-C bond, two O⁻ ligands.

Structure and Bonding

Molecular Geometry

The phosphoryl group, represented as >P=O, features a tetrahedral arrangement around the central phosphorus atom, arising from sp³ hybridization of the phosphorus 3s and 3p orbitals.^[13] This hybridization results in four equivalent sp³ orbitals, each forming a sigma bond: one to the oxygen atom and three to surrounding substituents, leading to an overall tetrahedral molecular geometry.^[14] The P=O linkage is often depicted as a double bond in simple representations, but resonance structures describe it as a shortened single bond with partial dative character from oxygen to phosphorus, contributing to the group's stability without altering the tetrahedral framework.^[15] In Lewis structures of phosphoryl compounds, the phosphorus is shown with 10 electrons in its valence shell, including a formal double bond to oxygen (P=O) and three single bonds to substituents, with the oxygen bearing lone pairs and the phosphorus a formal positive charge balanced by the negatively charged oxygen in resonance forms.^[13] This expanded octet accommodation is typical for phosphorus in the third period, enabling the tetrahedral coordination. Bond angles in such structures approximate the ideal tetrahedral value of 109.5°, though electronic and steric factors introduce distortions; for instance, in phosphoryl chloride (POCl₃), the O-P-Cl angles measure approximately 109.6° to 114.8°, while Cl-P-Cl angles are compressed to about 100.3° to 103°.^[16] Substituents attached to the phosphorus influence the precise geometry through steric interactions, which can compress or widen bond angles to relieve crowding. In trialkoxyphosphine oxides like (RO)₃P=O, bulky alkyl groups (e.g., isopropyl or tert-butyl) exert steric repulsion, leading to slight reductions in O-P-OR and R-O-P-OR angles compared to less hindered analogs, while maintaining overall tetrahedral symmetry.^[17] These distortions are more pronounced in sterically demanding systems, affecting molecular conformation without disrupting the core sp³ hybridization.^[18]

Bond Nature and Hybridization

The phosphorus atom in the phosphoryl group exhibits sp³ hybridization, forming four equivalent hybrid orbitals from its 3s and 3p atomic orbitals to accommodate the sigma framework of bonds to the terminal oxygen and three other substituents, resulting in a tetrahedral arrangement around phosphorus.^[19] In classical valence bond models, the apparent hypervalency of phosphorus, particularly in accommodating the P=O multiple bond, has been attributed to involvement of empty 3d orbitals, enabling expanded octet configurations through sp³d hybridization.^[20] However, contemporary quantum chemical analyses, such as those using density functional theory, reveal minimal 3d orbital participation, with hypervalency better explained by negative hyperconjugation or polarization effects rather than direct d-orbital bonding. The P=O bond in the phosphoryl group is characterized as a resonance hybrid between a classical double bond (P=O) and a zwitterionic dative structure (P⁺–O⁻), where the oxygen lone pair donates into an empty orbital on phosphorus, imparting partial multiple-bond character. This delocalization manifests in a shortened bond length of approximately 1.45–1.50 Å for the terminal P=O, significantly less than the 1.60–1.66 Å typical for single P–O bonds in the same compounds, as determined by X-ray crystallography and computational geometry optimizations. The coordinate bond aspect enhances electron density along the bond axis, contributing to its rigidity and resistance to cleavage. The bond dissociation energy of the P=O linkage typically ranges from 130 to 150 kcal/mol (544–628 kJ/mol), reflecting strong σ and π contributions that confer exceptional stability to phosphoryl compounds compared to analogous P–O single bonds (around 90 kcal/mol). Quantum chemical studies, including molecular orbital analyses, illustrate π-bonding as arising primarily from overlap between phosphorus 3p orbitals and oxygen 2p orbitals, forming filled bonding π molecular orbitals (often the HOMO) and empty antibonding π* counterparts, with limited augmentation from 3dπ–2pπ interactions in early models.^[20] These orbital interactions underpin the partial double-bond order (approximately 1.7–1.8) observed in bond length and spectroscopic data.

Physical and Chemical Properties

Physical Characteristics

Phosphoryl-containing compounds, particularly simple ones like phosphoryl chloride (POCl₃), typically appear as colorless fuming liquids with a pungent odor.^[21] For instance, POCl₃ has a density of 1.645 g/cm³ at 25°C and a boiling point of 105.5°C, reflecting its polar nature which contributes to relatively high boiling points compared to nonpolar analogs.^[22] These compounds exhibit high polarity, with POCl₃ possessing a dipole moment of 2.54 D arising from the P=O bond.^[23] Consequently, they are highly soluble in organic solvents such as benzene, chloroform, ether, and carbon tetrachloride, but react vigorously with water rather than dissolving stably.^[22] Spectroscopically, the P=O stretching vibration in phosphoryl compounds appears as a strong IR absorption band in the 1290–1320 cm⁻¹ region, as observed in POCl₃. In ³¹P NMR spectroscopy, chemical shifts for phosphoryl phosphorus atoms generally range from -50 to +50 ppm relative to phosphoric acid, with POCl₃ resonating at approximately +3 ppm, providing a diagnostic tool for structural identification.^[24]^[25]

Reactivity and Stability

The phosphoryl group, characterized by the P=O moiety with phosphorus in the +5 oxidation state, exhibits high reactivity toward nucleophiles due to the electrophilic nature of the phosphorus center. This reactivity is exemplified by the hydrolysis of phosphoryl trichloride (POCl₃), which proceeds stepwise with water acting as the nucleophile to displace chloride ions, ultimately yielding phosphoric acid (H₃PO₄) and hydrochloric acid (HCl). The reaction involves the formation of metastable intermediates such as phosphorodichloridic acid (PO₂Cl₂H), which can accumulate and pose safety risks due to their energetic nature, as detected by in situ ³¹P NMR and Raman spectroscopy. In the +5 oxidation state, the phosphoryl phosphorus is resistant to further oxidation, representing the highest stable oxidation level commonly observed in phosphorus compounds, with no significant redox changes occurring at the central atom under typical conditions.^[26] This stability arises from the tetrahedral coordination around phosphorus, where the P=O double bond and surrounding substituents satisfy its valence without requiring additional electron acceptance. Nucleophilic substitution reactions at the phosphorus atom are a hallmark of phosphoryl group reactivity, enabling the formation of various phosphorus derivatives. In the Arbuzov reaction, trialkyl phosphites (P(III) precursors to phosphoryl compounds) react with alkyl halides via initial nucleophilic attack by phosphorus on carbon, followed by intramolecular substitution at phosphorus by the halide ion, yielding dialkyl alkylphosphonates with the characteristic P=O group.^[27] This process highlights the facility of pentacoordinate intermediates in transforming trivalent to pentavalent phosphorus species.^[27] The stability of phosphoryl-containing compounds can be enhanced by electron-withdrawing substituents, which stabilize developing charges during reactions and influence decomposition pathways. For instance, in phosphoryl halides and related monohalides like tetra-aryloxyphosphorus derivatives, electron-withdrawing groups on aryloxy substituents promote thermal decomposition to aryl halides and triaryl phosphates via selective bond cleavage.^[28] Such substituents reduce electron density at phosphorus, mitigating unwanted side reactions while facilitating controlled reactivity under heating.^[28]

Synthesis and Preparation

Laboratory Methods

One common laboratory method for preparing phosphoryl group-containing compounds involves the oxidation of phosphines or phosphites to the corresponding phosphine oxides or phosphates. For instance, trialkyl phosphites can be oxidized to trialkyl phosphates using hydrogen peroxide as the oxidant, typically in a solvent such as dichloromethane or without solvent under mild conditions at room temperature. ^[29] This reaction proceeds via the addition of the peroxide to the phosphorus center, forming the P=O bond, and is widely used due to its simplicity and high efficiency, often achieving yields exceeding 95% after workup. ^[29] Another established technique is the reaction of phosphorus pentachloride (PCl₅) with oxygen sources, such as sulfur dioxide (SO₂), to produce phosphoryl chloride (POCl₃). In this procedure, PCl₅ is reacted with SO₂ gas in a sealed vessel or under controlled atmosphere at elevated temperatures around 100–150°C, yielding POCl₃ and thionyl chloride (SOCl₂) as a byproduct. ^[30] This method is suitable for small-scale synthesis in research settings, leveraging the reactivity of PCl₅ toward oxygen transfer. ^[30] A specific variant for POCl₃ preparation entails the reaction of phosphorus trichloride (PCl₃) with dichlorine monoxide (Cl₂O) under inert atmosphere conditions, such as nitrogen or argon, to prevent side reactions with moisture. The reaction is typically conducted by adding Cl₂O dropwise to PCl₃ heated to 50–60°C, followed by distillation of the product. ^[31] Reported yields for this process range from 70–90%, depending on the purity of reagents and control of temperature. ^[32] A key method for incorporating the phosphoryl group into organic molecules is the Arbuzov reaction, where trialkyl phosphites react with alkyl halides to form dialkyl alkylphosphonates, which contain the phosphoryl moiety. This rearrangement typically occurs under heating (80–150°C) without solvent, proceeding via a phosphonium salt intermediate, and is widely used for synthesizing phosphate and phosphonate esters with yields often above 80%. ^[33] Purification of these phosphoryl compounds is essential for achieving analytical purity in laboratory applications. For volatile liquids like POCl₃, fractional distillation under reduced pressure is the primary method, often collecting the fraction boiling at approximately 110°C to separate from impurities such as unreacted chlorides or byproducts. ^[31] For solid phosphoryl derivatives, such as certain phosphine oxides, recrystallization from suitable solvents like ethanol or acetone is employed to enhance purity by selectively dissolving and precipitating the compound based on solubility differences. ^[34] These techniques ensure the removal of contaminants while maintaining the integrity of the phosphoryl functionality.

Industrial Routes

The primary industrial route for producing phosphoryl chloride (POCl₃), a key phosphoryl compound, involves the thermal process starting from elemental phosphorus. In the burner process, white phosphorus (P₄) is combusted in a furnace at high temperatures (approximately 1,500–2,700°C) with air or oxygen to yield phosphorus pentoxide (P₄O₁₀), which serves as an intermediate in phosphoric acid production. This P₄O₁₀ is then reacted with phosphorus pentachloride (PCl₅, prepared from PCl₃ and Cl₂) in a controlled step according to the equation:

\mathrm{P_4O_{10} + 6 PCl_5 \rightarrow 10 POCl_3}

This method is favored for its efficiency in large-scale operations, where the reaction occurs in continuous reactors to minimize energy loss and maximize yield. The process is part of the broader thermal phosphoric acid manufacturing, where P₄O₁₀ can be hydrated to H₃PO₄, but diversion to POCl₃ supports downstream phosphoryl derivative synthesis.^[35]^[36] An alternative industrial pathway for POCl₃ synthesis is the direct oxidation of phosphorus trichloride (PCl₃) with oxygen, conducted continuously at 50–60°C via a radical mechanism in dedicated reaction vessels, followed by fractional distillation for purification. This route accounts for a significant portion of global output and is integrated into phosphorus halide production chains. For specialized phosphoryl compounds like alkyl phosphoryl chlorides (e.g., dialkyl phosphorochloridates), continuous flow reactions are employed, particularly in pesticide manufacturing, where POCl₃ is sequentially reacted with alcohols under controlled conditions to form intermediates such as (RO)₂POCl. These processes enhance scalability and safety by enabling precise temperature and reagent control, reducing batch variability.^[37]^[38] Economically, global production of POCl₃ was approximately 200,000 tonnes per year as of 2004, with major capacities in OECD countries (around 150,000 tonnes) and the remainder in non-OECD regions; it serves as a critical intermediate for flame retardants, comprising about 55% of its application in plastics and elastomer additives via phosphate ester formation. Environmental management in these routes focuses on containing volatile byproducts, including HCl generated during handling or inadvertent hydrolysis of POCl₃, which is captured via scrubbing systems to prevent acidic emissions. Phosphorus-containing wastes are minimized through recycling of unreacted P₄O₁₀ or PCl₃, while overall effluent controls address potential eutrophication from phosphoric acid traces, ensuring compliance with water pollution standards.^[37]^[37]

Biological Significance

Role in Phosphorylation

The phosphoryl group (−PO₃²⁻) plays a central role in phosphorylation, a key post-translational modification in biological systems where it is covalently attached to biomolecules such as proteins, lipids, or sugars, often activating or deactivating enzymes and altering their function.^[39] This process is essential for regulating metabolic pathways, as the addition of the negatively charged phosphoryl group can induce conformational changes in target molecules, thereby modulating their activity or interactions.^[40] For instance, phosphorylation of serine, threonine, or tyrosine residues in proteins can switch enzymes between active and inactive states, facilitating dynamic control over cellular processes.^[41] The mechanism of phosphoryl transfer typically involves a nucleophilic attack by the hydroxyl group (ROH) of the target biomolecule on the γ-phosphorus atom of adenosine triphosphate (ATP), the primary phosphate donor, resulting in the cleavage of the phosphoanhydride bond and release of adenosine diphosphate (ADP).^[42] This inline substitution reaction proceeds through a trigonal bipyramidal transition state, stabilized by the enzyme's active site, and can be represented by the equation:

\text{ATP} + \text{ROH} \rightarrow \text{ROPO}_3^{2-} + \text{ADP}

The reaction is energetically favorable due to the high-energy phosphoanhydride bond in ATP, with the standard free energy change (ΔG°′) for ATP hydrolysis to ADP and inorganic phosphate (Pi) being approximately −7.3 kcal/mol under physiological conditions, providing the driving force for phosphoryl transfer.^[43] Enzymes known as kinases catalyze the forward phosphorylation reaction by positioning the substrates and facilitating the nucleophilic attack, while phosphatases reverse the process through hydrolysis of the phosphoester bond, removing the phosphoryl group.^[44] These enzymes ensure precise and reversible control, with over 500 protein kinases identified in the human genome that specifically transfer the phosphoryl group to target residues.^[45] The strength of the P=O bond in the phosphoryl group contributes to its suitability for such transfers, as it resists hydrolysis while allowing efficient enzymatic catalysis.^[44] In signal transduction pathways, phosphorylation by kinases serves as a molecular switch, propagating extracellular signals to intracellular responses and regulating processes like the cell cycle.^[46] For example, cyclin-dependent kinases phosphorylate key proteins to drive progression through cell cycle phases, such as G1 to S transition, enabling timely DNA replication and cell division.^[47] Dysregulation of these phosphorylation events can lead to uncontrolled signaling, underscoring the phosphoryl group's critical role in maintaining cellular homeostasis.^[48]

Presence in Biomolecules

The phosphoryl group is a fundamental component in various biomolecules, most prominently in nucleotides where it serves as the phosphate moiety in energy-carrying molecules. In adenosine triphosphate (ATP), the phosphoryl groups are designated as α (attached directly to the 5' carbon of the ribose sugar), β (the middle phosphate), and γ (the terminal phosphate), forming a triphosphate chain that stores high-energy bonds. Adenosine diphosphate (ADP) retains the α- and β-phosphoryl groups after hydrolysis of the γ-phosphate from ATP, while adenosine monophosphate (AMP) contains only the α-phosphoryl group linked to the ribose. These structures enable the sequential release of energy through phosphoryl group transfer in cellular processes.^[49] In nucleic acids, the phosphoryl group forms the diester backbone of DNA and RNA, linking the 3'-hydroxyl of one deoxyribose (in DNA) or ribose (in RNA) sugar to the 5'-hydroxyl of the adjacent sugar via phosphodiester bonds. This sugar-phosphoryl diester arrangement creates a stable polymeric chain that supports genetic information storage and transmission, with the negatively charged phosphoryl oxygens conferring resistance to hydrolysis in DNA. Phospholipids, essential for cell membrane structure, incorporate the phosphoryl group in molecules like phosphatidylcholine, where it connects a glycerol backbone—esterified with two fatty acid chains—to a choline head group, forming an amphipathic structure that assembles into lipid bilayers. Coenzymes such as nicotinamide adenine dinucleotide (NAD+) feature phosphoryl groups in a pyrophosphate linkage between two ribose sugars, one attached to the adenine base and the other to the nicotinamide, facilitating redox reactions in metabolism. In proteins, the phosphoryl group attaches to the hydroxyl side chain of serine residues to form O-phosphoserine, a common post-translational modification that modulates protein function and interactions. The ubiquity of the phosphoryl group underscores its structural role, exemplified by the human body's daily ATP turnover of approximately 50-75 kg, reflecting constant recycling in energy-demanding tissues.^[50]^[51]^[52]^[53]

Applications and Uses

In Organic and Inorganic Synthesis

The phosphoryl group is frequently introduced in organic synthesis using phosphorus oxychloride (POCl₃) as a versatile reagent. POCl₃ also enables esterifications by reacting with alcohols to form phosphate esters, where stepwise substitution of its chloride ligands yields mono-, di-, or trialkyl phosphates, often in the presence of bases to neutralize HCl byproduct.^[54] In organophosphorus chemistry, the Michaelis-Arbuzov reaction exemplifies the utility of phosphoryl group incorporation for C-P bond formation. This classic transformation involves the nucleophilic attack of a trialkyl phosphite on an alkyl halide, followed by a rearrangement that installs the phosphoryl moiety, producing dialkyl alkylphosphonates as shown:

(RO)_3P + R'X \rightarrow (RO)_2P(O)R' + RX

The reaction's broad substrate scope, accommodating primary, secondary, and allylic halides, makes it indispensable for synthesizing phosphonates used as intermediates in agrochemicals and ligands.^[55] Microwave-assisted variants accelerate the process, enhancing yields and reducing reaction times while maintaining high selectivity.^[56] For inorganic applications, phosphoryl-containing compounds like triphenyl phosphate (TPP) are synthesized from POCl₃ and phenol via sequential esterification, replacing all three chlorides to form the triester. TPP acts as an effective flame retardant by promoting char formation and radical scavenging in polymeric materials such as PVC and polyurethane foams.^[57] This synthesis can be scaled industrially with high efficiency, achieving up to 97% isolated yields under controlled aqueous conditions.^[57] The inherent reactivity of phosphoryl reagents underscores their advantages in forming C-P bonds for pharmaceutical applications, where such linkages improve metabolic stability and target affinity in drugs like bisphosphonates for osteoporosis treatment. Seminal methods, including Arbuzov-type reactions, have enabled the preparation of over 20 clinically approved phosphorus-containing therapeutics, highlighting their impact on drug design.^[58]

In Biochemical and Catalytic Processes

Artificial kinases and phosphatases, designed to mimic natural phosphorylation and dephosphorylation, have emerged as tools for studying protein regulation and facilitating drug design. These synthetic systems often employ non-hydrolyzable phosphoserine mimics, such as those installed via expressed protein ligation or genetic code expansion, to create stable analogs of phosphorylated proteins that resist phosphatase activity.^[59] For instance, the PermaPhosSer method uses an autonomous E. coli expression system to incorporate non-hydrolyzable phosphoserine into proteins like sfGFP and 14-3-3 complexes, achieving yields up to 120 mg/L and enabling precise dissection of phosphorylation's role in protein-protein interactions, which informs the development of kinase-targeted therapeutics for diseases like cancer.^[60] Proximity-based modulators, such as peptide-binding modules, further enhance these mimics by promoting targeted phosphorylation of proteins of interest, aiding in the validation of drug candidates that alter kinase/phosphatase signaling pathways.^[61] In catalytic processes, phosphoryl transferases play a key role in biocatalytic cascades through efficient ATP regeneration systems. Polyphosphate kinases (PPKs), for example, catalyze the reversible transfer of phosphoryl groups from polyphosphate to ADP, sustaining ATP levels.^[62] Engineered variants like ChPPK D82N-K103E have demonstrated 4.3-fold higher specific activity, enabling high-yield biocatalytic production of compounds such as L-theanine (62.7 g/L, 90.1% conversion in 6 hours) and glutamine (13.8 g/L, 94.4% conversion in 4 hours).^[62] Similarly, carbohydrate kinases facilitate the phosphorylation of sugars like D-tagatose to form 1,6-bisphosphate derivatives, serving as intermediates in metabolic pathways, with the process noted for high efficiency in scaled biocatalytic systems.^[63] Phosphoryl groups enhance enzyme functionality in biosensors by enabling specific detection of phosphorylation events. Phosphoryl-modified peptides or proteins, captured via Phos-tag-biotin complexes that bind phosphomonoesters in the presence of Zn²⁺, allow electrochemical biosensors to monitor kinase activity with detection limits as low as 0.15 unit/mL for protein kinase A.^[64] This approach amplifies signals through enzymatic coupling, providing real-time insights into signaling cascades for diagnostic applications. In drug delivery, phosphoryl chitosan derivatives form amphiphilic micelles that improve solubility and bioavailability of therapeutics. N-octyl-N'-phthalyl-O-phosphoryl chitosan (OPPC), for example, encapsulates paclitaxel for oral delivery, achieving enhanced absorption and antitumor efficacy in vivo due to its mucoadhesive and pH-responsive properties.^[65] Recent advances in the 2020s have introduced phosphoryl-based organocatalysts for asymmetric synthesis, focusing on P-stereogenic centers. Bifunctional iminophosphorane catalysts enable desymmetrization of prochiral phosphine oxides, yielding P(V)-stereogenic compounds with up to 98% ee in two-stage processes.^[66] Hydrogen-bond donor organocatalysts, such as thioureas, promote kinetic resolution of secondary phosphine oxides via allylation, achieving high enantioselectivity (up to 99% ee) on gram scales.^[66] These methods have been applied to synthesize antiviral agents like remdesivir, using bicyclic imidazole catalysts for dynamic kinetic resolution with 96% conversion and 22:1 stereoselectivity.^[66]

References

[1]
https://www.annualreviews.org/doi/10.1146/annurev-biochem-060409-092741
[2]
Phosphoryl - an overview | ScienceDirect Topics
Phosphoryl group transfer reactions add or remove phosphoryl groups to or from cellular metabolites and macromolecules, and play a major role in biochemistry.
[3]
18.2: ATP and Phosphoryl Transfer Reactions - Chemistry LibreTexts
Aug 29, 2014 · Phosphoryl groups are derivatives of phosphoric acid, a strong acid that is commonly used in the laboratory. The fully deprotonated conjugate ...Missing: biochemistry | Show results with:biochemistry
[4]
PHOSPHORYL Definition & Meaning - Merriam-Webster
The meaning of PHOSPHORYL is a usually trivalent group PO ... Word History. Etymology. International Scientific Vocabulary. First Known Use. 1858, in the ...
[5]
https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Map%3A_Essential_Organic_Chemistry_(Bruice)/18%3A_The_Organic_Chemistry_of_Metabolic_Pathways/18.2%3A_ATP_and_Phosphoryl_Transfer_Reactions
[6]
What is the Difference Between Phosphoryl Group and Phosphate ...
Sep 21, 2021 · The key difference between phosphoryl group and phosphate group is that phosphoryl group contains one phosphorus atom bound to three oxygen atoms and -2 charge.<|control11|><|separator|>
[7]
Blue Book P-60-65 - IUPAC nomenclature
Sections P-62 to P-66 include compounds that are named, in substitutive nomenclature, by suffixes and prefixes, and by means of other types of nomenclature.
[8]
https://www.sigmaaldrich.com/US/en/product/aldrich/437891
[9]
phosphoramides (P04566) - IUPAC
Compounds in which one or more of the OH groups of phosphoric acid have been replaced with an amino or substituted amino group; commonly confined to the ...Missing: nomenclature | Show results with:nomenclature
[10]
[PDF] BlueBookV2.pdf - IUPAC nomenclature
Nomenclature of Organic Chemistry. IUPAC Recommendations and Preferred Names 2013. Prepared for publication by Henri A. Favre and Warren H. Powell,. Royal ...
[11]
biochemical phosphorus - IUPAC nomenclature
The full text of the IUPAC and IUBMB nomenclature of phosphorus-containing compounds of biochemical importance. ... However, "phosphoryl" is retained in derived ...
[12]
https://goldbook.iupac.org/terms/view/P04564
[13]
phosphono (P04564) - IUPAC
A prefix indicating the presence of the group − P ( = O ) ( OH ) A 2 . ... Citation: 'phosphono' in IUPAC Compendium of Chemical Terminology, 5th ed.Missing: definition | Show results with:definition
[14]
Phosphorus oxychloride
**Summary of POCl3 (Phosphorus Oxychloride) from PubChem:**
[15]
https://chemistry.ucsd.edu/undergraduate/student-resources/CHEM40-Chapter09-UCSD-ED-23-24.pdf
[16]
[PDF] Chapter 9: Phosphate transfer reactions - Organic Chemistry
Finally, phosphates are excellent leaving groups in biological organic reactions, as we will see many times throughout the remainder of this book. Clearly, an ...
[17]
https://www.mdpi.com/1422-0067/24/18/14087
[18]
Influence of the Substituent's Size in the Phosphinate Group ... - MDPI
Sep 14, 2023 · In general, the use of bulky substituents in phosphinate groups can limit the free rotation of the molecule and affect the coordination packing ...
[19]
[PDF] Conformational Analysis of Phosphoryl Compounds with ...
Attention is concentrated to the steric orientation of the phosphoryl group and the substituents at the α-carbon atom. Data concerning different phase ...
[20]
3d orbitals and bonds of second row atoms. 2. π bonding in ...
The concept of 3dπ orbital bonding in molecules of second row atoms is tested by making some model calculations on phosphoryl molecules, X3PO.<|separator|>
[21]
Phosphorus oxychloride | POCl3 | CID 24813 - PubChem
Phosphorus oxychloride appears as a colorless fuming liquid with a pungent odor. Density 14.0 lb / gal. Very toxic by inhalation and corrosive to metals and ...
[22]
Phosphorus oxitrichloride | 10025-87-3 - ChemicalBook
Jan 27, 2025 · CAS No. 10025-87-3. Chemical Name: Phosphorus oxitrichloride. Synonyms: POCl3;PHOSPHORYL CHLORIDE;PHOSPHOROUS OXYCHLORIDE;PHOSPHORYL ...Missing: IUPAC | Show results with:IUPAC
[23]
https://www.stenutz.eu/chem/solv6.php?name=phosphorus%20oxychloride
[24]
Investigation of the 31P NMR chemical shift dependence of ...
Investigation of the 31P NMR chemical shift dependence of phosphoryl compounds on the inductive and resonance effects of substituents.
[25]
A31P NMR study of some adducts of phosphorus oxychloride
The solid state 31P NMR spectra of some adducts of POCl3 with Lewis acids is reported. From the chemical shifts observed, both of those whose structure has ...
[26]
Chapter 1: Introduction to Phosphorus Chemical Biology - Books
Oct 30, 2020 · The second aspect of phosphate chemistry is that the central P atom in the [+5] oxidation state is electron deficient. It reacts as an ...
[27]
Improvements, Variations and Biomedical Applications of the ...
Mar 21, 2022 · The classical Michaelis–Arbuzov reaction entails a reaction between an alkyl halide and a trialkyl phosphite to yield a dialkylalkylphosphonate.
[28]
56. The organic chemistry of phosphorus. Part IV. The thermal ...
The thermal decomposition of tetra-aryloxyphosphorus monohalides : a new method for the preparation of aryl halides. D. G. Coe, H. N. Rydon and B. L. Tonge ...
[29]
US3277217A - Process for producing phosphate esters by oxidation ...
Process for producing phosphate esters by oxidation of phosphites using hydrogen peroxide and organic peroxides as catalyst.Missing: standard | Show results with:standard
[30]
[PDF] Industrial Preparation Methods of Chemical Solvents and Reagents
preparation consists in reacting phosphorus pentachloride (PCl5) and SO2. (Scheme 1). This method is extremely expensive, because it uses PCl5 as reactant ...
[31]
Preparation of phosphorus oxychloride - PrepChem.com
When the reaction is complete, phosphorus oxychloride is distilled. Further purification is performed by re-distillation and collecting fraction boiling at 110° ...Missing: phosphoryl chloride
[32]
Phosphoryl chloride - Sciencemadness Wiki
Jun 16, 2024 · Solubility, Reacts with alcohols, carboxylic acids. Soluble in benzoyl chloride, bromine, bromoacetic acid, carbon disulfide, liq. Cl2, liq. HBr ...
[33]
Oxidation of Phosphites and Phosphines via Quaternary ...
Oxidation of Phosphites and Phosphines via Quaternary Phosphonium Salts. Click to copy article linkArticle link copied! · The Journal of Organic Chemistry.Missing: laboratory phosphoryl
[34]
[PDF] AP-42, CH 8.9: Phosphoric Acid - EPA
Thermal process phosphoric acid manufacture, as shown schematically in Figure 8.9-2, involves 3 major steps: (1) combustion, (2) hydration, and (3) demisting.
[35]
CHAPTER 14: Phosphorus Oxychloride: Production and Use - Books
May 20, 2022 · Two main processes are used on an industrial scale. The first is the oxidation of phosphorus trichloride (PCl3) by reaction with a stream of ...
[36]
[PDF] PHOSPHORYL TRICHLORIDE CAS N°: 10025-87-3
Oct 7, 2025 · Phosphorus oxychloride (POCl(3)) is an intermediate in the synthesis of many organophosphorus insecticides and chemical warfare nerve gases that ...
[37]
US3927179A - Process for manufacturing phosphorus oxychloride
This method can be carried out by reacting phosphorus trichloride with sodium chlorate to yield the phosphorus oxychloride. However, certain economic factors ...
[38]
The crucial role of protein phosphorylation in cell signaling and its ...
This reversible mechanism occurs through protein kinases and consists of the addition of a phosphate group (PO4) to the polar group R of various amino acids.
[39]
Phosphorylation | Thermo Fisher Scientific - US
... phosphatases reverse protein phosphorylation by hydrolyzing the phosphate group. ... Kinases are enzymes that facilitate phosphate group transfer to substrates.
[40]
Phosphorylation of Proteins - Wiley Online Library
Mar 15, 2019 · Protein phosphorylation is a reversible process in which addition of phosphoryl group is mediated by protein kinases, and dephosphorylation occurs due to the ...
[41]
12.2: Phosphoryl Group Transfers and ATP - Biology LibreTexts
Aug 23, 2025 · Here is the chemical equation as recommended by the IUBMB/IUPAC: ... phosphoryl group. This section differentiates between enzyme classes ...
[42]
Metabolic Energy - The Cell - NCBI Bookshelf - NIH
In the hydrolysis of ATP to ADP plus phosphate (Pi), ΔG°′= -7.3 kcal/mol. Recall, however, that ΔG°′ refers to “standard conditions,” in which the ...
[43]
How do kinases transfer phosphoryl groups? - ScienceDirect.com
This review focuses primarily on the crystal structures of enzyme–substrate complexes of kinases and, in particular, what these structures tell us about the ...
[44]
Insights into the Phosphoryl Transfer Mechanism of Human ... - Nature
Dec 2, 2016 · This near attack position is favorable for the nucleophilic substitution reaction. The ATP binding pocket consists of five highly conserved ...
[45]
Role of Protein Phosphorylation in the Regulation of Cell Cycle and ...
In eukaryotes, protein phosphorylation plays a key role in cell signaling, gene expression, and differentiation. Protein phosphorylation is also involved in ...Abstract · Introduction · Identification of Phospho... · MinD, a Signaling Scaffold...
[46]
Cyclin-dependent protein kinases and cell cycle regulation ... - Nature
Jan 13, 2025 · Signal transduction is heavily reliant on the activity of protein kinases which, by catalyzing protein phosphorylation, control many ...
[47]
The regulation of protein phosphorylation - Portland Press
Jul 22, 2009 · Protein kinases regulate signalling pathways and cellular processes that mediate metabolism, transcription, cell-cycle progression, differentiation, ...The Kinome And Phylogeny · Glycogen Phosphorylase: An... · Protein Kinase Inhibitors
[48]
Physiology, Adenosine Triphosphate - StatPearls - NCBI Bookshelf
The structure of ATP is a nucleoside triphosphate, consisting of a nitrogenous base (adenine), a ribose sugar, and three serially bonded phosphate groups. ATP ...
[49]
Cell Membranes | Learn Science at Scitable - Nature
The hydrophilic head is composed of a choline structure (blue) and a phosphate (orange). This head is connected to a glycerol (green) with two hydrophobic tails ...Missing: phosphoryl- | Show results with:phosphoryl-
[50]
NAD(H) and NADP(H) Redox Couples and Cellular Energy ... - NIH
NADP+, a structural analogue of NAD+, is synthesized by transferring a phosphate group from ATP to the 2′-hydroxyl group of the adenosine ribose moiety of NAD+ ...Biosynthesis Of Nad In... · De Novo Synthesis Of Nad · Nad(h) And Nadp(h) Regulate...
[51]
Phosphorylation mechanism and structure of serine‐arginine protein ...
Dec 14, 2010 · SR proteins are phosphorylated at numerous serines in the RS domain by the SR-specific protein kinase (SRPK) family of protein kinases.
[52]
Energy Metabolism and Balance - IntechOpen
The turnover of the ATP molecule is extremely high; it is about 100–150 moles per day in resting conditions. This corresponds to 50–75 kg of newly formed ATP ...2. Energy Metabolism · Table 1 · 3. Energy Expenditure
[53]
Vilsmeier Haack Reaction - an overview | ScienceDirect Topics
The Vilsmeier-Haack reaction uses DMF and POCl₃ to form an iminium chloride intermediate, used for formylation of aromatic rings.
[54]
Use of XtalFluor-E as an Alternative to POCl3 in the Vilsmeier ...
Jul 10, 2018 · We report the use of XtalFluor-E ([Et2NSF2]BF4) as an alternative to POCl3 in the Vilsmeier–Haack formylation reaction of C-2-glycals.<|separator|>
[55]
Review on Modern Advances of Chemical Methods for the ...
On the mechanism, the first step of the Arbuzov reaction is nucleophilic attack by the phosphorus atom of the trialkyl phosphite at the electrophilic alkyl ...
[56]
THE MICHAELIS-ARBUZOV REACTION: Phosphorus, Sulfur, and ...
The microwave enhanced Michaelis-Arbuzov reaction shows remarkable rate acceleration under microwave irradiation and allows the facile synthesis, and in certain ...<|separator|>
[57]
Green Synthesis of Triaryl Phosphates with POCl3 in Water - 2017
Dec 4, 2017 · POCl3 is electrophilic and thereby facilitates a nucleophilic (PhO−) attack on the phosphorus results in P−Cl bond breaking (the P−Cl bond ...Missing: phosphoryl | Show results with:phosphoryl
[58]
Development and Clinical Application of Phosphorus-Containing ...
This review summarized the phosphorus-containing drugs currently on the market as well as a few promising molecules at clinical studies.
[59]
Synthetic Approaches to Protein Phosphorylation - PMC
Jul 18, 2015 · This review describes several chemical and biochemical methods that are under development and in current use to install phospho-amino acids and their mimics ...
[60]
PermaPhosSer: autonomous synthesis of functional, permanently ...
Installing stable, functional mimics of phosphorylated amino acids into proteins offers a powerful strategy to study protein regulation.
[61]
Modulating the phosphorylation status of target proteins through ...
PBMs promote the spatial proximity of POIs to kinases/phosphatases, and thus alter the phosphorylation state of POIs.
[62]
A high-throughput dual system to screen polyphosphate kinase ...
Aug 3, 2023 · At present, many enzymes have been reported to be used for ATP regeneration, such as pyruvate kinase (PK), creatine kinase (CK), acetate kinase ...
[63]
The Power of Biocatalysts for Highly Selective and Efficient ... - MDPI
The main goal of this review is to highlight the current state of the art and advances in highly selective biocatalytic phosphorylation reactions, fundamental ...
[64]
A sensitive electrochemical biosensor for detection of protein kinase ...
Highlights · A sensitive electrochemical method is developed for kinase activity assay. · Phos-tag-biotin is used as recognition element for phosphate group.
[65]
phthalyl-O-phosphoryl chitosan derivative as an effective oral carrier ...
Mar 1, 2019 · Herein, we describe a novel amphipathic chitosan derivative (N-octyl-N'-phthalyl-O-phosphoryl chitosan, abbreviated as OPPC) as an effective ...
[66]
Organocatalytic asymmetric synthesis of P-stereogenic molecules
This review will focus on organocatalytic strategies and introduces the most recent developments of stereoselective access to P-stereogenic compounds.