Intramolecular Charge-Assisted Hydrogen Bond Strength in Pseudochair Carboxyphosphate

Abstract

Carboxyphosphate, a suspected intermediate in ATP-dependent carboxylases, has not been isolated nor observed directly by experiment. Consequently, little is known concerning its structure, stability, and ionization state. Recently, carboxyphosphate as either a monoanion or dianion has been shown computationally to adopt a novel pseudochair conformation featuring an intramolecular charge-assisted hydrogen bond (CAHB). In this work, additive and subtractive correction schemes to the commonly employed open–closed method are used to estimate the strength of the CAHB. Truhlar’s Minnesota M06-2X functional with Dunning’s aug-cc-pVTZ basis set has been used for geometry optimization, energy evaluation, and frequency analysis. The CHARMM force field has been used to approximate the Pauli repulsive terms in the closed and open forms of carboxyphosphate. From our additive correction scheme, differential Pauli repulsion contributions between the pseudochair (closed) and open conformations of carboxyphosphate are found to be significant in determining the CAHB strength. The additive correction modifies the CAHB prediction (ΔEclosed–open) of −14 kcal/mol for the monoanion and −12 kcal/mol for the dianion to −22.9 and −18.4 kcal/mol, respectively. Results from the subtractive technique reinforce those from our additive procedure, where the predicted CAHB strength ranges from −17.8 to −25.4 kcal/mol for the monoanion and from −15.7 to −20.9 kcal/mol for the dianion. Ultimately, we find that the CAHB in carboxyphosphate meets the criteria for short-strong hydrogen bonds. However, carboxyphosphate has a unique energy profile that does not result in the symmetric double-well behavior of low-barrier hydrogen bonds. These findings provide deeper insight into the pseudochair conformation of carboxyphosphate, and lead to an improved mechanistic understanding of this intermediate in ATP-dependent carboxylases.

Coenzymes and Their Role in the Evolution of Life

“…Biotically, this anhydride is presumed to form from bicarbonate and ATP prior to transfer onto biotin but it has not been isolated nor observed directly by experiment. [144] However, biotin-free transfer is also well-established, for example, the use of carbamoyl phosphate (H 2 N(O)C-OPO 3 H 2 ) in pyrimidine biosynthesis. Furthermore, several alternative C 1 building blocks that are more electrophilic than carbon dioxide and that are of prebiotic relevance have been covered in this account.…”

“…Unlike most other coenzymes, biotin alone is chemically rather inert and only exerts its coenzymatic role in multienzyme systems with carboxyphosphate (HO 2 C‐OPO 3 H 2 ) as the substrate. Biotically, this anhydride is presumed to form from bicarbonate and ATP prior to transfer onto biotin but it has not been isolated nor observed directly by experiment [144] . However, biotin‐free transfer is also well‐established, for example, the use of carbamoyl phosphate (H 2 N(O)C‐OPO 3 H 2 ) in pyrimidine biosynthesis.…”

“…Unlike most other coenzymes,b iotin alone is chemically rather inert and only exerts its coenzymatic role in multienzyme systems with carboxyphosphate (HO 2 C-OPO 3 H 2 )a s the substrate.B iotically,t his anhydride is presumed to form from bicarbonate and ATPprior to transfer onto biotin but it has not been isolated nor observed directly by experiment. [144] However,b iotin-free transfer is also well-established, for example,t he use of carbamoyl phosphate (H 2 N(O)C-OPO 3 H 2 )i np yrimidine biosynthesis.F urthermore,s everal alternative C 1 building blocks that are more electrophilic than carbon dioxide and that are of prebiotic relevance have been covered in this account. These include guanidine ((H 2 N) 2 C = NH, 24), cyanic acid (HCNO), cyanamide (H 2 NCN, 26), and urea (27).…”

Coenzyme und ihre Rolle in der Evolution des Lebens

“…[143] Biotin (64) Im Unterschied zu den meisten anderen Coenzymen ist Biotin chemisch eher inert und übt seine coenzymatische Rolle nur in Multi-Enzym-Systemen mit Carboxyphosphat (HO 2 C-OPO 3 H 2 )a ls Substrat aus.B iotisch wird dieses Anhydrid vor der Übertragung auf Biotin aus Bicarbonat und ATPg ebildet, aber es konnte bisher weder isoliert noch experimentell direkt beobachtet werden. [144] Allerdings ist auch die Biotin-freie Übertragung gut etabliert, z. B. die Verwendung von Carbamoylphosphat (H 2 N(O)C-OPO 3 H 2 )b ei der Pyrimidin-Biosynthese.…”

Bazı karboksilik asitlerden elde edilen proton transfer tuzlarının ve Cu (II) komplekslerinin sentezi ve karakterizasyonu

“…Bir amin ve bir karboksilik asit tarafından oluşturulan proton transfer tuzu bir veya iki molekül arasında çok yönlü bağlantı oluşturabilir [15,16]. Yük-destekli hidrojen bağlarının etkileşiminin gücü nötr hidrojen bağı etkileşimlerinden daha fazladır [19][20]. Yaygın olarak yük-destekli veya yük aktarımıyla oluşan hidrojen bağları N + -H O -son zamanlarda araştırmacıların dikkatini çekmeye devam etmektedir [21,22].…”