Amino Acid Crystal Structures Research Articles

Synthesis, experimental and in silico studies of N-fluorenylmethoxycarbonyl-O-tert-butyl-N-methyltyrosine, coupled with CSD data: a survey of interactions in the crystal structures of Fmoc-amino acids.

Recently, fluorenylmethoxycarbonyl (Fmoc) amino acids (e.g. Fmoc-tyrosine or Fmoc-phenylalanine) have attracted growing interest in biomedical research and industry, with special emphasis directed towards the design and development of novel effective hydrogelators, biomaterials or therapeutics. With this in mind, a systematic knowledge of the structural and supramolecular features in recognition of those properties is essential. This work is the first comprehensive summary of noncovalent interactions combined with a library of supramolecular synthon patterns in all crystal structures of amino acids with the Fmoc moiety reported so far. Moreover, a new Fmoc-protected amino acid, namely, 2-{[(9H-fluoren-9-ylmethoxy)carbonyl](methyl)amino}-3-{4-[(2-hydroxypropan-2-yl)oxy]phenyl}propanoic acid or N-fluorenylmethoxycarbonyl-O-tert-butyl-N-methyltyrosine, Fmoc-N-Me-Tyr(t-Bu)-OH, C29H31NO5, was successfully synthesized and the structure of its unsolvated form was determined by single-crystal X-ray diffraction. The structural, conformational and energy landscape was investigated in detail by combined experimental and in silico approaches, and further compared to N-Fmoc-phenylalanine [Draper et al. (2015). CrystEngComm, 42, 8047-8057]. Geometries were optimized by the density functional theory (DFT) method either in vacuo or in solutio. The polarizable conductor calculation model was exploited for the evaluation of the hydration effect. Hirshfeld surface analysis revealed that H...H, C...H/H...C and O...H/H...O interactions constitute the major contributions to the total Hirshfeld surface area in all the investigated systems. The molecular electrostatic potentials mapped over the surfaces identified the electrostatic complementarities in the crystal packing. The prediction of weak hydrogen-bonded patterns via Full Interaction Maps was computed. Supramolecular motifs formed via C-H...O, C-H...π, (fluorenyl)C-H...Cl(I), C-Br...π(fluorenyl) and C-I...π(fluorenyl) interactions are observed. Basic synthons, in combination with the Long-Range Synthon Aufbau Modules, further supported by energy-framework calculations, are discussed. Furthermore, the relevance of Fmoc-based supramolecular hydrogen-bonding patterns in biocomplexes are emphasized, for the first time.

Crystal structures of amino acids: investigations into CSD

Crystal structures of amino acids: investigations into CSD

One Hydrogen Bond—Two Ways To Build a Structure. The Role of N–H···O Hydrogen Bonds in Crystal Structures of N,N-Dimethylglycine

Crystal structures of amino acids are considered to mimic important interactions in peptides; therefore the studies of the structure-forming factors in these systems attract much attention. N,N-Dimethylglycine is an interesting model compound that was used to test the role of the N–H···O hydrogen bonds in forming the head-to-tail chains, the main structural unit in the crystals of amino acids. It was hypothesized previously [Kolesov, B. A.; Boldyreva, E. V. J. Raman Spectrosc. 2010, 41, 670−677] that additional side N–H···O hydrogen bonds play an important role in forming the head-to-tail chains of amino acid zwitterions linked via N–H···O hydrogen bonds between the charged −NH3+ and −COO– terminal groups. The twice methylated amino group of N,N-dimethylglycine is able to form only one N–H···O hydrogen bond in the crystal structure, so this hypothesis could be tested. In the present article, we describe the crystal structures of two polymorphs of N,N-dimethylglycine, in which the zwitterions are packed in...

FTIR and Raman Vibrational Investigations on the Complex of Pyridine with Tartaric Acid

Amino acids are the building blocks of proteins and an important class of molecules, which are found to exhibit characteristic aggregation patterns in their crystal structures. Especially, the head-to-tail hydrogen bonding patterns that have been observed in the crystal structures of amino acids are of intrinsic interest pertaining to characteristic aggregation patterns. Carboxylic acids are simple organic molecules that are believed to have existed in the prebiotic earth and some of them are key intermediates in the biosynthesis of organic acids. Pyridine is used as a precursor to agrochemicals and pharmaceuticals and is also an important solvent and reagent. Tartaric acid is used as an antioxidant and its derivatives have a plethora of uses in the field of pharmaceuticals. For example, tartaric acid has been used in the production of effervescent salts, in combination with citric acid, in order to improve the taste of oral medications. In the present investigation, the complete vibrational analysis of the title compound is carried out in detail using FTIR and FT Raman measurements.

The effect of partial methylation of the glycine amino group on crystal structure inN,N-dimethylglycine and its hemihydrate

N,N-Dimethylglycine, C(4)H(9)NO(2), and its hemihydrate, C(4)H(9)NO(2)·0.5H(2)O, are discussed in order to follow the effect of the methylation of the glycine amino group (and thus its ability to form several hydrogen bonds) on crystal structure, in particular on the possibility of the formation of hydrogen-bonded `head-to-tail' chains, which are typical for the crystal structures of amino acids and essential for considering amino acid crystals as mimics of peptide chains. Both compounds crystallize in centrosymmetric space groups (Pbca and C2/c, respectively) and have two N,N-dimethylglycine zwitterions in the asymmetric unit. In the anhydrous compound, there are no head-to-tail chains but the zwitterions form R(4)(4)(20) ring motifs, which are not bonded to each other by any hydrogen bonds. In contrast, in the crystal structure of N,N-dimethylglycinium hemihydrate, the zwitterions are linked to each other by N-H···O hydrogen bonds into infinite C(2)(2)(10) head-to-tail chains, while the water molecules outside the chains provide additional hydrogen bonds to the carboxylate groups.

IR low-temperature matrix, X-ray and ab initio study on l-isoserine conformations

The IR low-temperature Ar and Kr matrix spectra of l-isoserine were registered for the first time and interpreted by means of the anharmonic DFT frequencies calculated at the B3LYP/aug-cc-pVTZ and B3LYP/aug-cc-pVDZ levels. 54 l-isoserine conformers were predicted to be stable at the B3LYP/aug-cc-pVDZ level. Population of the 8 most stable conformers was based on the QCISD/aug-cc-pVDZ energies, corrected for thermal anharmonic factors obtained at the B3LYP/aug-cc-pVDZ level. We found several conformers to be present in the measured matrices and conformer 1 to be dominating. Presence of the conformer 2 is well confirmed by the nu(C=O) band at 1790 cm(-1) and two bands at 1380 and 1350 cm(-1). Presence of the conformer 4 is quite well confirmed by the nu(C-O) bands at 1120 and 1095 cm(-1). Slightly weaker arguments are found for the observation of conformers 6 and 3. Calculations on 54 neutral and 5 zwitterionic conformers in water at the IEF-PCM/B3LYP/aug-cc-pVDZ level suggest that one neutral and one zwitterionic conformer co-exist in the aqueous environment. The crystal structure of l-isoserine was solved by X-ray diffraction analysis. The compound crystallizes without solvent in the chiral P2(1)2(1)2 space group. The asymmetric unit contains a single molecule. The molecule is in its zwitterionic form with the CH(2)-NH(3) side chain in the gauche conformation with respect to the hydroxyl group and in the anti conformation with respect to the carboxylate group. The structure of l-isoserine is dominated by a set of intermolecular hydrogen bonds. The strongest one appears between the OH and COOH groups of two neighbouring molecules: the O...H contact is of 1.66(2) A, which is amongst the shortest H-bonds of this kind observed in amino acid crystal structures.

Solvent-free crystallizations of amino acids: The effects of the hydrophilicity/hydrophobicity of side-chains

This work studied the self-assembling (crystallizing) behaviour of amino acids in the absence of solvent and additives (by sublimation and deposition in vacuum), instead of from aqueous solution. It is found that the hydrophilicity/hydrophobicity of side-chains can significantly affect the crystallization of amino acids in the absence of solvent. Crystal structures of amino acids having hydrophobic side-chains ( l-valine, l-leucine, l-isoleucine and l-methionine) obtained from sublimation are the same with those obtained from aqueous solution. New polymorphs for six amino acids are thought to have been obtained, based on X-ray diffraction and IR data for three of them ( l-tyrosine, l-Phyenylalanine and l-tryptophan), and just IR data for the other three ( l-alanine, l-proline and l-threonine).

On the application of an experimental multipolar pseudo-atom library for accurate refinement of small-molecule and protein crystal structures

With an increasing number of biomacromolecular crystal structures being measured to ultra-high resolution, it has become possible to extend to large systems experimental charge-density methods that are usually applied to small molecules. A library has been built of average multipole populations describing the electron density of chemical groups in all 20 amino acids found in proteins. The library uses the Hansen & Coppens multipolar pseudo-atom model to derive molecular electron density and electrostatic potential distributions. The library values are obtained from several small peptide or amino acid crystal structures refined against ultra-high-resolution X-ray diffraction data. The library transfer is applied automatically in the MoPro software suite to peptide and protein structures measured at atomic resolution. The transferred multipolar parameters are kept fixed while the positional and thermal parameters are refined. This enables a proper deconvolution of thermal motion and valence-electron-density redistributions, even when the diffraction data do not extend to subatomic resolution. The use of the experimental library multipolar atom model (ELMAM) also has a major impact on crystallographic structure modelling in the case of small-molecule crystals at atomic resolution. Compared to a spherical-atom model, the library transfer results in a more accurate crystal structure, notably in terms of thermal displacement parameters and bond distances involving H atoms. Upon transfer, crystallographic statistics of fit are improved, particularly free R factors, and residual electron-density maps are cleaner.

Effect of pressure on the crystal structure of L-serine-I and the crystal structure of L-serine-II at 5.4 GPa

The crystal structure of L-serine has been determined at room temperature at pressures between 0.3 and 4.8 GPa. The structure of this phase (hereafter termed L-serine-I), which consists of the molecules in their zwitterionic tautomer, is orthorhombic, space group P212121. The least compressible cell dimension (c), corresponds to chains of head-to-tail NH...carboxylate hydrogen bonds. The most compressible direction is along b, and the pressure-induced distortion in this direction takes the form of closing up voids in the middle of R-type hydrogen-bonded ring motifs. This occurs by a change in the geometry of hydrogen-bonded chains connecting the hydroxyl groups of the -CH2OH side chains. These hydrogen bonds are the longest conventional hydrogen bonds in the system at ambient pressure, having an O...O separation of 2.918 (4) A and an O...O...O angle of 148.5 (2) degrees ; at 4.8 GPa these parameters are 2.781 (11) and 158.5 (7) degrees . Elsewhere in the structure one NH...O interaction reaches an N...O separation of 2.691 (13) A at 4.8 GPa. This is amongst the shortest of this type of interaction to have been observed in an amino acid crystal structure. Above 4.8 GPa the structure undergoes a single-crystal-to-single-crystal phase transition to a hitherto uncharacterized polymorph, which we designate L-serine-II. The OH...OH hydrogen-bonded chains of L-serine-I are replaced in L-serine-II by shorter OH...carboxyl interactions, which have an O...O separation of 2.62 (2) A. This phase transition occurs via a change from a gauche to an anti conformation of the OH group, and a change in the NCalphaCO torsion angle from -178.1 (2) degrees at 4.8 GPa to -156.3 (10) degrees at 5.4 GPa. Thus, the same topology appears in both crystal forms, which explains why it occurs from one single-crystal form to another. The transition to L-serine-II is also characterized by the closing-up of voids which occur in the centres of other R-type motifs elsewhere in the structure. There is a marked increase in CH...O hydrogen bonding in both phases relative to L-serine-I at ambient pressure.

Topological analysis of experimental electron densities

Practical computing algorithms are described for analysing the topology of experimental electron density distributions represented as either three-dimensional grid densities or multipolar pseudoatom superpositions. The algorithms are implemented in the programNEWPROP, results from which are illustrated with applications to twoN-acetyl,C-methylamide blocked amino acid crystal structures.

Ab initio 13C nuclear shielding calculations for some solid amino acids using the GIAO procedure

AbstractThe results of ab initio GIAO‐CHF 13C nuclear shielding calculations for some solid amino acids, performed with the 6—311G** and a locally dense basis set are reported. Comparison of the present calculation with the observed shieldings shows an RMS error of 6.6 ppm. Shieldings of the carbon nuclei which are multiply bonded are strongly influenced by electron correlation effects. Experimental molecular geometries used in these calculations were taken from crystal structures of amino acids.

X-ray studies on crystalline complexes involving amino acids and peptides: Part XVIII. Crystal structure of a new form of L-arginine D-glutamate and a comparative study of amino acid crystal structures containing molecules of the same and mixed chirality

The new form of L-arginine D-glutamate is monoclinic, P21, witha = 9.941(1),b = 4.668(2),c = 17.307(1) A,β = 95.27(1)°, and Z = 2. In terms of composition, the new form differs from the old form in that the former is a monohydrate whereas the latter is a trihydrate. The structure has been solved by the direct methods and refined to R = 0.085 for 1012 observed reflections. The conformation of the arginine molecule is the same in both the forms whereas that of the glutamate ion is different. The change in the conformation of the glutamate ion is such that it facilitates extensive pseudosymmetry in the crystals. The molecules arrange themselves in double-layers stabilised by head-to-tail sequences involving main chains, in both the forms. However, considerable differences exist between the two forms in the interface, consisting of side chains and water molecules, between double-layers. A comparative study of the relationship between the crystal structures of L and DL amino acids on the one hand and that between the structures of LL and LD amino acid-amino acid complexes on the other, provides interesting insights into amino acid aggregation and the effect of chirality on it. The crystal structures of most hydrophobic amino acids are made up of double-layers and those of most hydrophilic amino acids contain single layers, irrespective of the chiralities of the amino acids involved. In most cases, the molecules tend to appropriately rearrange themselves to preserve the broad features of aggregation patterns when the chirality of half the molecules is reversed as in the structures of DL amino acids. The basic elements of aggregation in the LL and the LD complexes, are similar to those found in the crystals of L and DL amino acids. However, the differences between the LL and the LD complexes in the distribution of these elements are more pronounced than those between the distributions in the structures of L and DL amino acids.

Structure of DL-lanthionine monohydrate: hydrogen-bonding patterns in amino acid crystal structures

Structure of DL-lanthionine monohydrate: hydrogen-bonding patterns in amino acid crystal structures

Three-center (bifurcated) hydrogen bonding in the crystal structures of amino acids

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThree-center (bifurcated) hydrogen bonding in the crystal structures of amino acidsG. A. Jeffrey and J. MitraCite this: J. Am. Chem. Soc. 1984, 106, 19, 5546–5553Publication Date (Print):September 1, 1984Publication History Published online1 May 2002Published inissue 1 September 1984https://doi.org/10.1021/ja00331a025RIGHTS & PERMISSIONSArticle Views289Altmetric-Citations74LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (682 KB) Get e-Alerts Get e-Alerts

Occurrence and geometrical features of head-to-tail sequences involving amino acids in crystal structures.

A careful study of the crystal structures of commonly occurring amino acids, and their racemates and complexes reveals that each hydrogen bond connecting the alpha-amino and the alpha-carboxylate groups and its symmetry equivalents generally give rise to an infinite head-to-tail sequence in which the two groups are periodically brought into close proximity. Such sequences, which have earlier been suggested to be of probable relevance to prebiotic polymerisation, appear to be an almost universal feature of amino acid aggregation in the solid state. These sequences belong to two main categories in terms of the geometrical arrangement of amino acid molecules in them. The sequences in the first category consist of straight chains of molecules related mostly by the shortest cell translation in the crystals. The sequences of the second category form hydrogen bonded two fold helices centred around crystallographic 2(1) screw axes. The sequences can be further sub-divided into different types on the basis of the geometrical features of the hydrogen bonds involved in them. A few sequences involving both L and D isomers have also been observed in the crystal structures of some DL-amino acids. The shortest cell translation in most crystals under consideration has a value in the neighbourhood of 5.3 A and corresponds to the periodicity of a straight head-to-tail sequence or, less frequently, that of a helical sequence or both. The crystal structures of amino acids and their complexes can be classified in terms of the occurrence and the geometrical disposition of different types of head-to-tail sequences in them.

A survey of hydrogen bond geometries in the crystal structures of amino acids

An analysis of the geometries of the hydrogen bonds observed by neutron diffraction in thirt-two crystal structures of amino acids shows the following results. Of the 168 hydrogen bonds in the data set, 64 involve the zwitterion groups  ▪ and  C O 2. Another 18 are from ▪ to sulphate or carbonyl oxygens. The majority, 46, of these ▪H … O bonds are three-centered (bifurcated). Nine are four-centered (trifurcated). The geometry in which the three-centered hydrogen bond involves both oxygens of the same carboxylate group is not especially favoured. When it does occur, one hydrogen bond is generally shorter and the other longer, than when the bonding involves oxygens on different carboxylate groups. The shortest hydrogen bonds are the OH … O C , from a carboxylic acid hydroxyl to a carboxylate oxygen, and NH … O C when the nitrogen is the ring atom in histidine or proline. Carboxylate groups, on average, accept six hydrogen bonds, with no examples of less than four bonds. The reason for the large number of three-centered ▪H … O C bonds is therefore a proton deficiency arising from the disparity between the tripled donor property of the ▪ groups and the sextuple, on average, acceptor property of the carboxylate groups. There is good geometrical evidence for the existence of H … O and H … Cl − hydrogen bonds, especially involving the hydrogen atoms on α-atoms.

Hydrogen-bonding geometry and patterns in carbohydrates and amino acids

The hydrogen-bond geometry observed by neutron diffraction of 24 carbohydrate and 32 amino acid crystal structures is analyzed and compared. Of the 100 OHO bonds in the carbohydrate structures, 25 were three-centered (bifurcated). This bigamous behavior is rationalized in terms of the 25% greater number of acceptor oxygens than donor hydroxyls and the need to preserve the “cooperative effect.” The predominant hydrogen bonds in the amino acids are the zwitterion type , 64 out of a total of 145. Of these, 51 are three-centered. Again the rationale appears to be an equilization of donor and acceptor functions, since each carboxylate group generally accepts between four and six hydrogen bonds.

Hydrogen bonds in crystal structures of amino acids, peptides and related molecules.

The results of a survey of 439 hydrogen bonds in 95 recently determined crystal structures of amino acids, peptides and related molecules suggest that the following generalizations hold true for linear (angle X-H---Y greater than 150 degrees) hydrogen bonds. (1) The charge on the acceptor group does not influence the length of a hydrogen bond. (2) For a given acceptor group, the hydrogen bond lengths increase in the order imidazolium N--H less than ammonium N-H less than guanidinium N-H; this order holds true for oxygen anion acceptor groups. Cl-ions and the uncharged oxygen of water molecules. (3) The uncharged imidazole N-H group forms shorter hydrogen than the amide N-H GROUP. (4) The carboxyl O-H groups form shorter hydrogen bonds than other hydroxyl groups. (5) The hydrogen bonds involving a halogen ion are longer than hydrogen bonds with other acceptors when corrected for their longer van der Walls radii. The observed differences between the lengths of hydrogen bonds formed by different donor and acceptor groups in amino acids and peptides, imply differences in the energetics of their formation.

N+‐HO bond lengths in crystal structures of amino acids and peptides

<i>N</i>⁺‐<i>H</i>O bond lengths in crystal structures of amino acids and peptides

ANALYSIS OF O‐H…O HYDROGEN BONDS*

Some geometrical parameters associated with the donor and the acceptor end of O‐H…O hydrogen bonds have been analysed. The data consist of 356 hydrogen bonds from reported crystal structures of amino acids, peptides and oligosaccharides. The following conclusions are arrived at:(a) The most probable range for the hydrogen bond length is between 2.7–2.8 å, the average being 2.76 å. When the donor is a water molecule the distribution is slightly different from the other cases. The average becomes 2.82 å, indicating that O‐H…O hydrogen bonds, where a water molecule acts as a donor, tend to be slightly larger.(b) The maximum in the distribution for the hydrogen bond angle (H‐O‥ .O) lies in the range 5°–10°, indicating that the O‐H…O hydrogen bonds tend to be slightly nonlinear, a feature similar to that for N‐H…O hydrogen bonds.(c) For carbonyl type of acceptor groups, the distribution of angle between O‥ .O (or H…O) and C = O extended shows a maximum in the range 50°–60° indicating a directional property towards the lone pair electrons.In order to study the effect of lone pair orbitals on the direction of orientation of the O‐H group the following parameters connected with the direction of lone pair orbitals are analysed and the main results are:(d) The elevation of O‥ .O (and H…O) direction from the acceptor plane (plane containing the lone pair orbitals), (ζ), shows a maximum in the range O°–10° indicating that the direction thus tends to lie close to the acceptor plane. For carbonyl acceptor groups, the distribution is uniform up to 30° and many of the larger values of ζ are found to occur for carbonyl acceptor groups only.(e) The distribution for the angle between the projection Oaccep.…Odonor (and Oaccep.…H) direction on the acceptor plane and the direction of the lone pair orbital (ζ) shows a maximum in the range O°–30°. The distribution is found to be dependent on the number of hydrogen bonds for which the same oxygen atom is the acceptor. The distribution for ζ shows a maximum between 20°–30° for those cases when the oxygen atom is recipient of only one hydrogen bond and the maximum occurs between O°–10° for those cases when the oxygen receives two hydrogen bonds.(f) The geometry in the limited number of examples where the oxygen is the recipient of three hydrogen bonds is also discussed.