Metal-Nucleotide Interactions: Crystal Structures of Alkali (Li+, Na+, K+) and Alkaline Earth (Ca2+, Mg2+) Metal Complexes of Adenosine 2'-Monophosphate

Crystal structures of lithium, sodium, potassium, calcium and magnesium salts of adenosine 2'-monophosphate (2'-AMP) have been obtained at atomic resolution by X-ray crystallographic methods. 2'-AMP.Li belongs to the monoclinic space group P21 with a = 7.472(3)Å, b = 26.853(6) Å, c = 9.184(1)Å, b = 113.36(1)Å and Z= 4. 2'-AMP.Na and 2'-AMP.K crystallize in the trigonal space groups P31 and P3121 with a = 8.762(1)Å, c = 34.630(5)Å, Z= 6 and a = 8.931(4), Åc = 34.852(9)Å and Z= 6 respectively while 2'-AMP.Ca and 2'-AMP.Mg belong to space groups P6522 and P21 with cell parameters a = 9.487(2), c = 74.622(13), Z = 12 and a = 4.973(1), b = 10.023(2), c = 16.506(2), beta = 91.1(0) and Z = 2 respectively. All the structures were solved by direct methods and refined by full matrix least-squares to final R factors of 0.033, 0.028, 0.075, 0.069 and 0.030 for 2'-AMP.Li, 2'-AMP.Na, 2'- AMP.K, 2'-AMP.Ca and 2'-AMP.Mg, respectively. The neutral adenine bases in all the structures are in syn conformation stabilized by the O5'-N3 intramolecular hydrogen bond as in free acid and ammonium complex reported earlier. In striking contrast, the adenine base is in the anti geometry (cCN = -156.4(2)°) in 2'-AMP.Mg. Ribose moieties adopt C2'-endo puckering in 2'-AMP.Li and 2'-AMP.Ca, C2'-endo-C3'-exo twist puckering in 2'-AMP.Na and 2'-AMP.K and a C3'-endo-C2'-exo twist puckering in 2'-AMP.Mg structure. The conformation about the exocyclic C4'-C5' bond is the commonly observed gauche-gauche (g+) in all the structures except the gauche- trans (g-) conformation observed in 2'-AMP.Mg structure. Lithium ions coordinate with water, ribose and phosphate oxygens at distances 1.88 to 1.99Å. Na+ ions and K+ ions interact with phosphate and ribose oxygens directly and with N7 indirectly through a water oxygen. A distinct feature of 2'-AMP.Na and 2'-AMP.K structures is the involvement of ribose O4' in metal coordination. The calcium ion situated on a two-fold axis coordinates directly with three oxygens OW1, OW2 and O2 and their symmetry mates at distances 2.18 to 2.42Å forming an octahedron. A classic example of an exception to the existence of the O5'-N3 intramolecular hydorgen bond is the 2'-AMP.Mg strucure. Magnesium ion forms an octahedral coordination with three water and three phosphate oxygens at distances ranging from 2.02 to 2.11Å. A noteworthy feature of its coordination is the indirect link with N3 through OW3 oxygen resulting in macrochelation between the base and the phosphate group. Greater affnity of metal clays towards 5' compared to 2' and 3' nucleotides (J. Lawless, E. Edelson, and L. Manring, Am. Chem. Soc. Northwest Region Meeting, Seattle. 1978) due to macrochelation infered from solution studies (S. S. Massoud, H. Sigel, Eur. J. Biochem. 179, 451-458 (1989)) and interligand hydrogen bonding induced by metals postulated from metal-nucleotide structures in solid state (V. Swaminathan and M. Sundaralingam, CRC. Crit. Rev. Biochem. 6, 245-336 (1979)) are borne out by our structures also. The stacking patterns of adenine bases of both 2'-AMP.Na and 2'-AMP.K structures resemble the 2'-AMP.NH4 structure reported in the previous article. 2'-AMP.Li, 2'-AMP.Ca and 2'-AMP.Mg structures display base-ribose O4' stacking. An overview of interaction of monovalent and divalent cations with 2' and 5'-nucleotides has been presented.

Trifurcated (four-center) hydrogen bond in solid state crystal structure of 5'-amino-5'-deoxyadenosine p-toluenesulfonate

The crystal structure of 5'-amino-5'-deoxyadenosine (5'-Am.dA) p-toluenesulfonate has been determined by X-ray crystallographic methods. It belongs to the orthorhombic space group P2(1)2(1)2(1) with a = 7.754(3)Angstrom, b = 8.065(1)Angstrom and c = 32.481(2)Angstrom. This nucleoside side shows a syn conformation about the glycosyl bond and C2'-endo-C3'-exo puckering for the ribose sugar. The orientation of N5' atom is gauche-trans about the exocyclic C4'-C5' bond. The amino nitrogen N5' forms a trifurcated hydrogen bond with N3, O9T and O4' atoms. Adenine bases form A.A.A triplets through hydrogen bonding between N6, N7 and N1 atoms of symmetry related nucleoside molecules.

Mechanisms of formation of the Arabian Sea mini warm pool in a high-resolution Ocean General Circulation Model

An Ocean General Circulation Model of the Indian Ocean with high horizontal (0.25 degrees x 0.25 degrees) and vertical (40 levels) resolutions is used to study the dynamics and thermodynamics of the Arabian Sea mini warm pool (ASMWP), the warmest region in the northern Indian Ocean during January-April. The model simulates the seasonal cycle of temperature, salinity and currents as well as the winter time temperature inversions in the southeastern Arabian Sea (SEAS) quite realistically with climatological forcing. An experiment which maintained uniform salinity of 35 psu over the entire model domain reproduces the ASMWP similar to the control run with realistic salinity and this is contrary to the existing theories that stratification caused by the intrusion of low-salinity water from the Bay of Bengal into the SEAS is crucial for the formation of ASMWP. The contribution from temperature inversions to the warming of the SEAS is found to be negligible. Experiments with modified atmospheric forcing over the SEAS show that the low latent heat loss over the SEAS compared to the surroundings, resulting from the low winds due to the orographic effect of Western Ghats, plays an important role in setting up the sea surface temperature (SST) distribution over the SEAS during November March. During March-May, the SEAS responds quickly to the air-sea fluxes and the peak SST during April-May is independent of the SST evolution during previous months. The SEAS behaves as a low wind, heat-dominated regime during November-May and, therefore, the formation and maintenance of the ASMWP is not dependent on the near surface stratification.

Long-term results of obstetric brachial plexus surgery

Background: Brachial plexus birth palsy (BPBP) most often occurs as a result of foetal-maternal disproportion. The C5 and C6 nerve roots of the brachial plexus are most frequently affected. In contrast, roots from the C7 to Th1 that result in total injury together with C5 and C6 injury, are affected in fewer than half of the patients. BPBP was first described by Smellie in 1764. Erb published his classical description of the injury in 1874 and his name became linked with the paralysis that is associated with upper root injury. Since then, early results of brachial plexus surgery have been reasonably well documented. However, from a clinical point of view not all primary results are maintained and there is also a need for later follow-up results. In addition most of the studies that are published emanate from highly specialized clinics and no nation wide epidemiological reports are available. One of the plexus injuries is the avulsion type, in which the nerve root or roots are ruptured at the neural cord. It has been speculated whether this might cause injury to the whole neural system or whether shoulder asymmetry and upper limb inequality results in postural deformities of the spine. Alternatively, avulsion could manifest as other signs and symptoms of the whole musculoskeletal system. In addition, there is no available information covering activities of daily living after obstetric brachial plexus surgery. Patients and methods: This was a population-based cross-sectional study on all patients who had undergone brachial plexus surgery with at least 5 years of follow-up. An incidence of 3.05/1000 for BPBP was obtained from the registers for this study period. A total of 1706 BPBP patients needing hospital treatment out of 1 717 057 newborns were registered in Finland between 1971 and 1997 inclusive. Of these BPBP patients, 124 (7.3%) underwent brachial plexus surgery at a mean age of 2.8 months (range: 0.4―13.2 months). Surgery was most often performed by direct neuroraphy after neuroma resection (53%). Depending on the phase of the study, 105 to 112 patients (85-90%) participated in a clinical and radiological follow-up assessment. The mean follow up time exceeded 13 years (range: 5.0―31.5 years). Functional status of the upper extremity was evaluated using Mallet, Gilbert and Raimondi scales. Isometric strength of the upper limb, sensation of the hand and stereognosis were evaluated for both the affected and unaffected sides then the differences and their ratios were calculated and recorded. In addition to the upper extremity, assessment of the spine and lower extremities were performed. Activities of daily living (ADL), participation in normal physical activities, and the use of physiotherapy and occupational therapy were recorded in a questionnaire. Results: The unaffected limb functioned as the dominant hand in all, except four patients. The mean length of the affected upper limb was 6 cm (range: 1-13.5 cm) shorter in 106 (95%) patients. Shoulder function was recorded as a mean Mallet score of 3 (range: 2―4) which was moderate. Both elbow function and hand function were good. The mean Gilbert elbow scale value was 3 (range: -1―5) and the mean Raimondi hand scale was 4 (range:1―5). One-third of the patients experienced pain in the affected limb including all those patients (n=9) who had clavicular non-union resulting from surgery. A total of 61 patients (57%) had an active shoulder external rotation of less than 0° and an active elbow extension deficiency was noted in 82 patients (77%) giving a mean of 26° (range: 5°―80°). In all, expect two patients, shoulder external rotation strength at a mean ratio 35% (range: 0―83%) and in all patients elbow flexion strength at a mean ratio of 41% (range: 0―79%) were impaired compared to the unaffected side. According to radiographs, incongruence of the glenohumeral joint was noted in 15 (16%) patients, whereas incongruence of the radiohumeral joint was found in 20 (21%) patients. Fine sensation was normal for 34/49 (69%) patients with C5-6 injury, for 15/31 (48%) with C5-7 and for only 8/25 (32%) of patients with total injury. Loss of protective sensation or absent sensation was noted in some palmar areas of the hand for 12/105 patients (11%). Normal stereognosis was recorded for 88/105 patients (84%). No significant inequalities in leg length were found and the incidence of structural scoliosis (1.7%) did not differ from that of the reference population. Nearly half of the patients (43%) had asynchronous motion of the upper limbs during gait, which was associated with impaired upper limb function. Data obtained from the completed questionnaires indicated that two thirds (63%) of the patients were satisfied with the functional outcome of the affected hand although one third of all patients needed help with ADL. Only a few patients were unable to participate in physical activities such as: bicycling, cross-country skiing or swimming. However, 71% of the patients reported problems related to the affected upper limb, such as muscle weakness and/or joint stiffness during the aforementioned activities. Incongruity of the radiohumeral joints, extent of the injury, avulsion type injury, age less than three months of age at the time of plexus surgery and inexperience of the surgeon was related to poor results as determined by multivariate analyses. Conclusions: Most of the patients had persistent sequelae, especially of shoulder function. Almost all measurements for the total injury group were poorer compared with those of the C5-6 type injury group. Most of the patients had asymmetry of the shoulder region and a shorter affected upper limb, which is a probable reason for having an abnormal gait. However, BPBP did not have an effect on normal growth of the lower extremities or the spine. Although, participation in physical activities was similar to that of the normal population, two-thirds of the patients reported problems. One-third of the patients needed help with ADL. During the period covered by this study, 7.3% BPBP of patients that needed hospital treatment had a brachial plexus operation, which amounts to fewer than 10 operations per year in Finland. It seems that better results of obstetric plexus surgery and more careful follow-up including opportunities for late reconstructive procedures will be expected, if the treatment is solely concentrated on by a few specialised teams.

Magnetic resonance imaging and ultrasonography in brachial plexus birth injury

Brachial plexus birth injury (BPBI) is caused by stretching, tearing or avulsion of the C5-C8 or Th1 nerve roots during delivery. Foetal-maternal disproportion is the main reason for BPBI. The goal of this study was to find out the incidence of posterior subluxation of the humeral head during first year of life in BPBI and optimal timing of the ultrasonographic screening of the glenohumeral joint. The glenohumeral congruity and posterior subluxation of the humeral head associated to muscle atrophy were assessed and surgical treatment of the shoulder girdle as well as muscle changes in elbow flexion contracture were evaluated. The prospective, population based part of the study included all neonates born in Helsinki area during years 2003-2006. Patients with BPBI sent to the Hospital for Children and Adolescents because of decreased external rotation, internal rotation contracture or deformation of the glenohumeral joint as well as patients with elbow flexion contracture were also included in this prospective study. The incidence of BPBI was calculated to be 3.1/1000 newborns in Helsinki area. About 80% of the patients with BPBI recover totally during the follow-up within the first year of life. Permanent plexus injury at the age of one year was noted in 20% of the patients (0.64/1000 newborns). Muscle imbalance resulted in sonographically detected posterior subluxation in one third of the patients with permanent BPBI. If muscle imbalance and posterior subluxation are left untreated bony deformities will develop. All patients with internal rotation contracture of the glenohumeral joint presented muscle atrophy of the rotator cuff muscles. Especially subscapular and infraspinous muscles were affected. A correlation was found particularly between greatest thickness of subscapular muscle and subluxation of the humeral head, degree of glenoid retroversion, as well as amount of internal rotation contracture. Supinator muscle atrophy was evident among all the studied patients with elbow flexion contracture. Brachial muscle pathology seemed to be an important factor for elbow flexion contracture in BPBI. Residual dysfunction of the upper extremity may require operative treatment such as tendon lengthening, tendon transfers, relocation of the humeral head or osteotomy of the humerus. Relocation of the humeral head improved the glenohumeral congruency among patients under 5 years of age. Functional improvement without remodeling of the glenohumeral joint was achieved by other reconstructive procedures. In conclusion: Shoulder screening by US should be done to all patients with permanent BPBI at the age of 3 and 6 months. Especially atrophy of the subscapular muscle correlates with glenohumeral deformity and posterior subluxation of the humeral head, which has not been reported in previous studies. Permanent muscle changes are the main reason for diminished range of motion of the elbow and forearm. Relocation of the humeral head, when needed, should be performed under the age of 5 years.

An infrared spectroscopic study of C7 intramolecular hydrogen bonds in peptides

The ir-spectra in the N-H stretching region of Piv-Pro-NHMe and Boc-Pro-NHMe have been studied in carbon tetrachloride and chloroform solutions over a wide range of concentrations. Based on the concentration dependence of the N-H stretching bands, it has been shown that the characteristic N-H stretching band due to the C7 intramolecular hydrogen bond is around 3335 cm-'. Intermolecular hydrogen bonding also occurs to a small extent in these peptides, giving rise to a slight concentration dependence of the N-H stretching bands. The band around 3335 cm-* need not necessarily be due to C7 hydrogen bonds alone as proposed by Tsuboi et al. or to intermolecular hydrogen bonding alone as proposed by Maxfield et al.; this conclusion is supported by studies on Boc-Leu-NHMe, which undergoes only intermolecular hydrogen bonding We have shown that 2-Aib-Aib-OMe and Z-Aib- Ala-OMe form C7 intramolecular hydrogen bonds in addition to C5 intramolecular hydrogen bonds. The present studies also show that all the peptides studied exist in more than one conformation in solution.

Anomalin. A Dihydropyranocoumarin Derivative from the Plant Lingusticum elatum

The title compound, 9,10-dihydro-8,8-dimethyl-2-oxo-2H,8H-benzo[1,2-b:3,4-b']dipyran-9,10-diyl 2-methyl-2-butenoate, C24H26O7, contains a highly planar coumarin nucleus and a substituted dihydropyran ring (C), which has a distorted half-chair conformation, with an 8 alpha,9 beta orientation. The conformation of ring C is further supported by the two angelyloxy (2-methyl-2-butenoyloxy) substituents at positions C9 and C10, which are cis oriented and thus cannot both occupy equatorial positions with respect to the plane of ring C. The conformations of the two angelyloxy substituents are different, as indicated by their endocyclic torsion angles. The most striking of these angles are O1'-C2'-C4'=C6' and O1'-C2'-C4'-C5' [-137.7 (5) and 43.7 (5)degrees, respectively, in the chain at C10 and 155.8 (5) and -24.7 (9)degrees, respectively in the chain at C9]. These variations are due to two intramolecular hydrogen bonds, namely, C16-H161 ... O1' [C16 ... O1' 3.056 (7) Angstrom] and C7''-H7Y ... O3'' [C7'' ... O3'' 2.955 (12) Angstrom]. The methyl substituents, C15 and C16, at position C8 are alpha and beta oriented, respectively. The crystal structure is stabilized by a weak C4-H41 ... O3' hydrogen bond [C4 ... O3' 3.297 (6) Angstrom] between the screw-related molecules.

Analysis of geometric and strain effects in homo-Diels-Alder reactions

Molecular mechanics calculations have been carried out to quantify the key geometric and strain effects which are likely to control the homo-Diels-Alder reactivity of 1,4-dienes. The criteria considered include C1..C5 and C2..C4 distances in the diene, twist angle of the two pi units, and the magnitude of strain increase as a result of cycloaddition. By first considering these factors in a number of non-conjugated dienes with known reactivity, the ranges of values within which the reaction is favoured are proposed. Calculations are also reported on several substrates which have not been investigated so far. Promising systems for experimental study are suggested which, in addition to being intrinsically interesting, would place the present proposals on a firm basis.

N-3-benzoyl-2 ',3 '-di-O-benzoyluridine

The structure of N-3-benzoyl-2',3'-di-O-benzoyluridine, C30H24N2O9, has two molecules in the asymmetric unit. The uracil bases of both the molecules are in the anti conformation with respect to the ribose moiety and the furanosyl rings adopt a C3'-endo conformation. The orientation about the C4'-C5' bond is gauche-gauche. The two crystallographically independent molecules are linked through several C-H ... O hydrogen bonds. The nucleoside molecules pack as columns along the a axis and these columns repeat along the c axis.

N-4-anisoylcytidine dihydrate

The title compound, C17H19N3O7. 2H(2)O, has C2'-endo, C3'-exo puckering, The orientation of the base with respect to the sugar is anti and the geometry about C4'-C5' is gauche,trans. The angle between the cytidine base and the phenyl ring of the anisoyl group is 15.5(2)degrees.

N-6-anisoyladenosine monohydrate

The title compound, C18H19N5O6. H2O, has a syn conformation about the glycosidic bond. Its furanose ring shows a C2'-endo-C3'-exo twist conformation and trans-gauche geometry about the C4'-C5' bond. The angle between the adenine base and the phenyl ring of the anisoyl group is 22.9 degrees. Adenine and anisoyl groups stack along the b axis at a separation of 3.4 Angstrom.

Structure, function, and mechanism of HhaI DNA methyltransferases

A vast amount of literature has accumulated on the characterization of DNA methyltransferases. The HhaI DNA methyltransferase, a C5-cytosine methyltransferase, has been the subject of investigation for the last 2 decades. Biochemical and kinetic characterization have led to an understanding of the catalytic and kinetic mechanism of the methyltransfer reaction. The HhaI methyltransferase has also been subjected to extensive structural analysis, with the availability of 12 structures with or without a cofactor and a variety of DNA substrates. The mechanism of base flipping, first described for the HhaI methyltransferase, is conserved among all DNA methyltransferases and is also found to occur in numerous DNA repair enzymes. Studies with other methyltransferase reveal a significant structural and functional similarity among different types of methyltransferases. This review aims to summarize the available information on the HhaI DNA methyltransferase.

Crystal Structure, Thermal Expansion and ElectricaH Conductivity of Yo.sCao.2Fel-x Mnx03+o (0 < x < 1.0)

The crystal structure, thennal expansion and electrical conductivity of the solid solutions YOgCao.2Fel-x MnxOJ+c5 (0 ~ x ~ 1.0) were investigated. All compositions had the GdFeOrtype orthorhombic perovskite structure with trace amounts of a second phase present in case of x = 0.8 and 1.0. The lattice parameters were detennined at room tempe'rature by using X-ray powder diffraction (XRPD). The pseudocubic lattice constant decreased with increasing x. The average I inear thermal expansion coefficient (anv) in the temperature range from 673 to 973 K showed negligible change with x up to x = 0.4. The thennal expansion curve for x = I had a slope approaching zero in the temperature range from 648 to 948 K. The calculated activation energy values for electrical conduction indicate that conduction occurs primarily by the small polaron hopping mechanism. The drastic drop in electrical conductivity for a small addition of Mn (0 ~ x ~ 0.2) is caused by the preferential fonnation of Mn4t ion~ (rather than Fe4 +) which act as carrier traps. This continues till the charge compensation for the divalent ions on the A-site is complete. The results indicate that with further increase in manganese content (beyond x =0.4) in the solid solutions, there is an increase in exc :::ss oxygen and consequently, a small increase in Mn'll il>I1~, which are charge compensated by the formation of cation vancancies.

Estimation of the 2.0(5) helix type i -> i hydrogen bond energy at Aib*-Oxa motif: an isodesmic approach

Bending at the valence angle N-C-alpha-C' (tau) is a known control feature for attenuating the stability of the rare intramolecular hydrogen bonded pseudo five-membered ring C-5 structures, the so called 2.0(5) helices, at Aib. The competitive 3(10)-helical structures still predominate over the C5 structures at Aib for most values of tau. However at Aib*, a mimic of Aib where the carbonyl 0 of Aib is replaced with an imidate N (in 5,6-dihydro-4H-1,3-oxazine = Oxa), in the peptidomimic Piv-Pro-Aib*-Oxa (1), the C(5)i structure is persistent in both crystals and in solution. Here we show that the i -> i hydrogen bond energy is a more determinant control for the relative stability of the C5 structure and estimate its value to be 18.5 +/- 0.7 kJ/mol at Aib* in 1, through the computational isodesmic reaction approach, using two independent sets of theoretical isodesmic reactions. (C) 2014 Elsevier Ltd. All rights reserved.

beta gamma-fused turn structures in sugar amino acid (SAA) containing cyclic tetrapeptides with alpha 3 delta architecture

The current manuscript describes conformational analysis of 15-membered cyclic tetrapeptides (CTPs), with alpha 3 delta architecture, containing sugar amino acids (SAA) having variation in the stereocenter at C5 carbon. Conformational analyses of both the series, in protected and deprotected forms, were carried out in DMSO-d(6) using various NMR techniques, supported by restrained MD calculations. It was intriguing to notice that the alpha 3 delta macrocycles got stabilized by both 10-membered beta-turn as well as a seven-membered gamma-turn, fused within the same macrocycle. The presence of fused sub-structures within a 15-membered macrocycle is rare to see. Also, the stereocenter variation at C5 did not affect the fused turn structures and exhibited similar conformations in both the series. The design becomes highly advantageous as fused reverse turn structures are occurring in the cyclic structure with minimalistic size macrocycle and this can be applied to develop suitable pharmacophores in the drug development process. (C) 2014 Elsevier Ltd. All rights reserved.