Hydrogen Bonding Donors and Acceptors

Interactions between hydrogen-bond donor and acceptor groups in different molecules play a pivotal role in many chemical and biological problems. Hydrogen bonds can be studied with quantum chemical calculations and empirical methods. 

Variations on the a helix in which the chain is either more loosely or more tightly coiled, with hydrogen bonds to residues n + 5 or n + 3 instead of n + 4 are called the n helix and 3io helix, respectively. The 3io helix has 3 residues per turn and contains 10 atoms between the hydrogen bond donor and acceptor, hence its name. Both the n helix and the 3to helix occur rarely and usually only at the ends of a helices or as single-turn helices. They are not energetically favorable, since the backbone atoms are too tightly packed in the 3io helix and so loosely packed in the n helix that there is a hole through the middle. Only in the a helix are the backbone atoms properly packed to provide a stable structure. 

Figure 7.4 The edges of the base pairs in DNA that ate in the major groove are wider than those in the minor groove, due to the asymmetric-attachment of the base pairs to the sugar-phosphate backbone (a). These edges contain different hydrogen bond donors and acceptors for potentially specific interactions with proteins (b).

The enantiophore query used in the search is derived from the CSP and directly built from a 3D structure model of the target CSP molecule, as it can be used today for the determination of new lead compounds [20, 21]. This procedure does not need an important modeling expertise. One can easily recognize the different center types in the receptor in question. These can be hydrogen-bond donors and acceptors, charged... 

Recently, more detailed parameters for hydrogen bonding bases have been introduced and applied to many reactions demonstrating the existence of a linear free energy relationship between the hydrogen bonding donor and acceptor abilities and many kinetic or thermodynamic parameters91. 

The sum of hydrogen bonding donor and acceptor related E-state descriptors are well correlated with the corresponding HYBOT parameters, with r2-values of 0.8-0.95 [38]. This gives the E-state descriptors a link to experimental values, which is positive but not necessary for the purpose of generating useful models with good statistical quality for, in this case, intestinal absorption. 

There are some very simple heuristic rules concerning cut-offs on molecular weight, number of hydrogen bond donors and acceptors as well as lipophilicity,... 

Oral bioavailability of a drug is primarily dependent upon its rate and extent of drug absorption and systemic clearance. Systemic clearance is primarily composed of hepatic, renal and biliary clearance. The PK properties are in turn directly impacted by the drug s physical properties, such as, log P, log D and pKa. The physical properties are in turn a function of the compound s structure, molecular weight, number of hydrogen bond donors and acceptors, and number of rotatable bonds. Oral bioavailability is the outcome from the dynamic interplay of these factors in the biological system. 

The effect of structural variation on crystal structure was studied for 12 phenyl-substituted derivatives of 6-amino-2-phenylsulfonylimino-l,2-dihydropyridine [37], The title compound contains both hydrogen bond donor and acceptor sites, and the... 

The LOCK AND KEY model for enzyme specificity uses complementarity between the enzyme active site (the lock) and the substrate (the key). Simply, the substrate must fit correctly into the active site—it must be the right size and shape, have charges in the correct place, have the right hydrogen-bond donors and acceptors, and have just the right hydrophobic patches. 

X-CW divinylbenzene polymer exchange, hydrogen bond donor and acceptor, and reversed phase activities basic drugs (94)... 

One of the simplest and most common ways to evaluate a molecule for ADME properties is a qualitative examination of its basic descriptor values such as molecular weight (MW), ClogP for lipophilicity, polar surface area (PSA), counts of hydrogen bond donors and acceptors (HBD, HBA), and count of rotatable bonds (RB). This type of approach popularized by Lipinski s famous Rule of 5 was published a decade ago [6]. Lipinski et al. established cutoffs for MW (500), ClogP (5), HBA (10), and HBD (5). These cutoffs were based on the 90th percentile of distributions of molecules in the World Drug Index having USAN or INN names. The Rule of 5 considers a violation of any two of these cutoffs to be an alert for poor absorption or permeability. 

Abstract Concave molecules with a periphery of complementary hydrogen-bond donors and acceptors dimerize to form non-covalently bound capsules. These host structures feature the ability to bind appropriate guest molecules... 

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