**6. Hydrogen bond strengths in phosphoramidates**

Histogram of the N…O distances in the N—H…O hydrogen bonds in compounds having a P(O)(N)n(O)3-n (n = 1, 2, 3) skeleton is given in Fig. 7. In this figure, the distribution of Hbond strength in different families of phosphoramidates are shown with different colored columns: compounds having a P(O)(NH)n(N)m(O)3-(n+m) skeleton (n = 1, 2; n+m < 3) as black

Phosphoramidates: Molecular Packing and Hydrogen

triamides having a C(O)NHP(O)[NH]2 fragment.

neighboring molecules from this frontier boundary.

simply accessible through a structural study.

**7. Some future aims and proposals** 

P(O)[NHC6H4(4-OCH3)]3 (WAWNIS [97]).

Bond Strength in Compounds Having a P(O)(N)n(O)3-n (n = 1, 2, 3) Skeleton 593

In this family, a long donor···acceptor distance (3.477(2) Å) is observed with a relatively linear N—H…O angle (171 (2)°) for the N—H···O(CH3) hydrogen bond in the packing of

In compounds having a C(O)NHP(O) fragment, the strongest N—H…O hydrogen bonds

some molecules [in the case of a *syn* orientation of P═O versus N—H which allows the building of the cyclic motif through a pair of P═O…H—NC(O)NHP(O) hydrogen bonds]. In this sub-category of compounds, the strongest and weakest hydrogen bonds are observed for the N…O distances in the ranges 2.70–2.80 Å [for NC(O)NHP(O)—H…O hydrogen bonds] and 3.00– 3.25 Å [for Namide—H…O hydrogen bonds], while in the range 2.80–3.00 Å for donor– acceptor distances both types of hydrogen bonds are found. In a recently published structure [129] with a NHC(O)NHP(O)[NH]2 skeleton, the intramolecular N—H…O hydrogen bonds are found in the range 2.65-2.70 Å (Fig. 7). The asymmetric unit contains four independent molecules and the hydrogen bond pattern is different from all phosphoric

Phosphorus has a very deep and widespread chemistry and understanding its nature in the compounds is noticeable interest. This may be achieved through the study on collective

The structural investigations and the study on the hydrogen-bond patterns may help to predict the molecular packing from the molecular structure. Moreover, as the biological activity of phosphorus compounds is very important, finding a relationship between the structure and a biological property is beneficial. For example, as well-known, a biological property may be related to the three important factors: lipophilicity, electronic and steric parameters. Probably, part of these factors could be well-understand by considering the crystal structure' study of such compounds; the electronic parameters may be related to the nature of chemical bonds or to the electron density or valence bond in different parts of the molecule. It is believed that, in the first step of interaction with acetylcholinesterase, the phosphoryl group is involving with the enzyme active site through a non-covalent bond; so, considering the non-covalent interaction of phosphoryl group with different atoms such as hydrogen helps to understand that the molecule how much could close to the enzyme active site. The steric parameters may be elucidated from the volume of molecule or considering the V(volume of unit cell)/Z(number of molecules in the unit cell). This may be in fact the practical volume which the molecule has, as the molecule usually cannot be closer to the

The solubility of molecules in different solvents must be checked in the crystal growth process; so, elucidation of lipophilicity is easy; however, the best method for measuring of this parameter is using of the spectrophotometer. And finally, the steric parameters can

Preparation of phosphorus acids of the formula RP(O)(OH)2 may develop the synthesis of the functionalized nano-phosphate materials and also polyoxometalate-based organic/inorganic hybrid compounds in which the phosphorus atom is trapping between

behaviors of phosphorus compounds in point of view of their different aspects.

2(8) rings of

are found for the P═O…H—NC(O)NHP(O) hydrogen bonds, especially in the R2

columns, C(O)NHP(O)(NH)2 and C(O)NHP(O)(N)2 as blue and P(O)(NH)x(N)3-x (x = 1, 2, 3) as red columns.

In phosphoramidates having a P(O)(NH)n(N)m(O)3-(n+m) skeleton (balck), the strongest and weakest N—H…O hydrogen bonds are found for hydrogen bonds in the range of 2.65 to 2.75 Å and 3.20 to 3.30 Å.

In compounds containing a P(O)(NH)x(N)3-x skeleton, the strongest N—H…O hydrogen bonds are seen for the HBs in the range of 2.70 to 2.80 Å. The phosphoryl group' involvement in a multi-centered P(O)···[H—N]n (n = 2 & 3) grouping may lead to some weak H-bonds; for example in P(O)[NHC(CH3)3]3 (KABVEP [93]), N…O distances & N—H…O angles are 3.255(4) Å & 111.1(2)°, 3.294(4) Å & 93.4(2)° and 3.159(4) Å & 123.0(2)°, and in P(O)[NH(C6H5)]3 (KEQLUO [95]) these parameters are 3.06 Å & 110° and 3.06 Å & 108°; this weakening of H-bond strength is attributed to the *anti*-cooperativity effect [89].

Fig. 7. Histogram of the N…O distances in the N—H…O hydrogen bonds in compounds having P(O)(NH)n(N)m(O)3-(n+m) (n = 1, 2; n+m < 3) (black), C(O)NHP(O)(NH)2 and C(O)NHP(O)(N)2 (blue), and P(O)(NH)x(N)3-x (x = 1, 2, 3) (red) skeletons (the co-crystals and solvated compounds and the compounds having a disorder in the sites involving HB interaction were not enumerated).

In this family, a long donor···acceptor distance (3.477(2) Å) is observed with a relatively linear N—H…O angle (171 (2)°) for the N—H···O(CH3) hydrogen bond in the packing of P(O)[NHC6H4(4-OCH3)]3 (WAWNIS [97]).

In compounds having a C(O)NHP(O) fragment, the strongest N—H…O hydrogen bonds are found for the P═O…H—NC(O)NHP(O) hydrogen bonds, especially in the R22(8) rings of some molecules [in the case of a *syn* orientation of P═O versus N—H which allows the building of the cyclic motif through a pair of P═O…H—NC(O)NHP(O) hydrogen bonds]. In this sub-category of compounds, the strongest and weakest hydrogen bonds are observed for the N…O distances in the ranges 2.70–2.80 Å [for NC(O)NHP(O)—H…O hydrogen bonds] and 3.00– 3.25 Å [for Namide—H…O hydrogen bonds], while in the range 2.80–3.00 Å for donor– acceptor distances both types of hydrogen bonds are found. In a recently published structure [129] with a NHC(O)NHP(O)[NH]2 skeleton, the intramolecular N—H…O hydrogen bonds are found in the range 2.65-2.70 Å (Fig. 7). The asymmetric unit contains four independent molecules and the hydrogen bond pattern is different from all phosphoric triamides having a C(O)NHP(O)[NH]2 fragment.
