Getting the chemistry right: protonation, tautomers and the importance of H atoms in biological chemistry

There are more H atoms than any other type of atom in an X-ray crystal structure of a protein–ligand complex, but as H atoms only have one electron they diffract X-rays weakly and are `hard to see'. The positions of many H atoms can be inferred by our chemical knowledge, and such H atoms can be added with confidence in `riding positions'. For some chemical groups, however, there is more ambiguity over the possible hydrogen placements, for example hydroxyls and groups that can exist in multiple protonation states or tautomeric forms. This ambiguity is far from rare, since about 25% of drugs have more than one tautomeric form. This paper focuses on the most common, `prototropic', tautomers, which are isomers that readily interconvert by the exchange of an H atom accompanied by the switch of a single and an adjacent double bond. Hydrogen-exchange rates and different protonation states of compounds (e.g. buffers) are also briefly discussed. The difference in heavy (non-H) atom positions between two tautomers can be small, and careful refinement of all possible tautomers may single out the likely bound ligand tautomer. Experimental methods to determine H-atom positions, such as neutron crystallography, are often technically challenging. Therefore, chemical knowledge and computational approaches are frequently used in conjugation with experimental data to deduce the bound tautomer state. Proton movement is a key feature of many enzymatic reactions, so understanding the orchestration of hydrogen/proton motion is of critical importance to biological chemistry. For example, structural studies have suggested that, just as a chemist may use heat, some enzymes use directional movement to protonate specific O atoms on phosphates to catalyse phosphotransferase reactions. To inhibit `wriggly' enzymes that use movement to effect catalysis, it may be advantageous to have inhibitors that can maintain favourable contacts by adopting different tautomers as the enzyme `wriggles'.

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Heterotopic ossification in the post cruciate ligament of the knee: a case report and literature review

BMC Musculoskeletal Disorders ◽

10.1186/s12891-021-04176-x ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Cun Li ◽

Zonggui Huang ◽

K. C. Anil ◽

Chendeng Lao ◽

Qianghua Wu ◽

...

Keyword(s):

Literature Review ◽

Heterotopic Ossification ◽

Knee Pain ◽

Cruciate Ligament ◽

Complete Recovery ◽

X Rays ◽

Related Factors ◽

Knee Motion ◽

Adequate Treatment ◽

The Difference

Abstract Background Heterotopic ossification (HO) is noted most frequently in periarticular muscles and has not yet been reported in the cruciate ligaments of the knee. We present a rare case of symptomatic ossification of the posterior cruciate ligament (PCL). Case presentation A 59-year-old woman had a 2-year history of knee pain that was getting worse during knee motion and had restricted knee motion for 1 year. X-rays could not show the lesion clearly. Multi-planar computed tomography demonstrated ossification within the PCL with mild osteoarthritic changes and excluded any other intra-articular pathology. The patient underwent arthroscopic debridement and then experienced immediate relief of pain and complete recovery of range of motion. Conclusion This is the first report of HO in the PCL as a possible cause of knee pain and restricted knee motion. On the basis of literature review, this case elaborates the difference between HO and calcification in the ligaments, the related factors inducing HO and the undefined pathogenesis, and favorable prognosis after adequate treatment.

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The Difference in Backscatter Factors of Diagnostic X-rays by the Difference in the Scattering Medium and in the Objective Dose

Japanese Journal of Radiological Technology ◽

10.6009/jjrt.2016_jsrt_72.10.1007 ◽

2016 ◽

Vol 72 (10) ◽

pp. 1007-1014

Author(s):

Hideki Kato ◽

Keita Sakai ◽

Mizuki Uchiyama ◽

Kentaro Suzuki

Keyword(s):

X Rays ◽

Scattering Medium ◽

The Difference ◽

Backscatter Factors

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Magnetic Structure of Multilayers from Soft-X-Ray Magnetic Circular Dichroism

MRS Proceedings ◽

10.1557/proc-375-59 ◽

1994 ◽

Vol 375 ◽

Cited By ~ 2

Author(s):

C. T. Chen ◽

Y. U. Idzerda ◽

C.-C. Kao ◽

L. H. Tjeng ◽

H.-J. Lin ◽

...

Keyword(s):

Thin Films ◽

Circular Dichroism ◽

Magnetic Circular Dichroism ◽

Magnetic Thin Films ◽

X Rays ◽

X Ray ◽

Specific Manner ◽

Left And Right ◽

The Difference ◽

Circular Dichroïsm

AbstractSoft-x-ray magnetic circular dichroism (MCD) is the difference between the absorptivity or reflectivity of left and right circularly polarized soft-x-rays at the magnetically interesting L2,3- edges of 3d transition metals or the M4,5-edges of the 4f rare earth elements. Thanks to its large absorption cross-section and strong MCD effect, this technique has become a powerful new means for probing, in an element- and site-specific manner, the magnetic properties of ultra-thin films and multilayers. Soft-x-ray MCD experiments, recently conducted at the Dragon beamline, are utilized to demonstrate the recent progress in this technique and its applications in the research of magnetic thin films.

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The sensitivity of atomic analysis by X-rays

Proceedings of the Royal Society of London. Series A, Containing Papers of a Mathematical and Physical Character ◽

10.1098/rspa.1932.0058 ◽

1932 ◽

Vol 135 (828) ◽

pp. 637-656 ◽

Cited By ~ 3

Keyword(s):

Atomic Number ◽

Target Material ◽

High Sensitivity ◽

Major Constituent ◽

X Rays ◽

Depth Of Penetration ◽

X Ray ◽

Constituent Element ◽

The Difference ◽

Atomic Analysis

In a previous paper it was shown that 0·0007 per cent, of 29 Cu and 0·0003 per cent, of 26 Fe could be detected in 30 Zn by atomic analysis by X-ray spectroscopy. This sensitivity is greater than that which was claimed by Noddack, Tacke, and Berg, who set the limit at about 0·1 per cent, for non-metals, and by Hevesy, who stated it to be about 0·01 per cent, for an element present in an alloy. It was later suggested by Hevesy that the high value of the sensitivity which we found might result from the fact that some of the alloys we had used were composed of elements of almost equal atomic number, and that the sensitivity would be smaller for a constituent of low atomic number mixed with a major constituent of high atomic number. To elucidate these disagreements we have made further observations of the sensitivity with elements of different atomic number and have investigated the conditions which can influence the sensitivity. The Factors Determining Sensitivity . The detection of one element in a mixture of elements depends upon the identification of its K or L lines in the general spectrum emitted by the mixture under examination. The intensity with which these lines are excited in the target (“excited intensity”) is proportional to the number of atoms of the constituent element excited, i. e ., to its concentration and to the volume of the target in which the cathode ray energy is absorbed. The depth of penetration of the cathode rays is determined by the density of the target material and by their velocity ( i. e ., by the voltage applied to the X-ray tube). Schonland has shown that the range of homogeneous cathode rays in different elements, expressed as a mass per unit area, is approximately constant and is independent of the atomic number of the absorbing element. When their velocity is increased, the cathode rays will penetrate to a greater depth, and therefore a greater number of atoms of all constituents will be ionised. This will increase the “excited intensity” of the lines due to the particular constituent sought equally with those lines of the other elements present. The intensity of a line further depends upon the difference between the voltage applied to the X-ray tube and that necessary to excite the series. For these reasons, a high applied voltage is required for a high sensitivity.

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Dietary Vitamin B6 Deficiency Impairs Gut Microbiota and Host and Microbial Metabolites in Rats

Biomedicines ◽

10.3390/biomedicines8110469 ◽

2020 ◽

Vol 8 (11) ◽

pp. 469

Author(s):

Shyamchand Mayengbam ◽

Faye Chleilat ◽

Raylene A. Reimer

Keyword(s):

Gut Microbiota ◽

Vitamin B6 ◽

Dietary Vitamin ◽

Enzymatic Reactions ◽

Sprague Dawley ◽

Microbial Composition ◽

Metabolic Markers ◽

Vitamin B6 Deficiency ◽

The Difference ◽

The Impact

Vitamin B6 plays a crucial role as a cofactor in various enzymatic reactions but bacteria-produced vitamin B6 is not sufficient to meet host requirements. Our objective was to assess the impact of diet-derived vitamin B6 on gut microbiota and host serum metabolomics. Sprague–Dawley rats (n = 47) were fed a control, low B6 (LB6) or high B6 (HB6) diet for six weeks. Serum and cecal samples were collected for biochemical, metabolomics and gut microbiota profiling. There was a significant sex effect for gut microbiota and several metabolic markers. Bodyweight and percent body fat were significantly reduced in LB6 compared to control and HB6 rats. Microbial beta-diversity differed significantly between LB6 and the control and HB6 rats in both sexes. Lachnospiraceae_NK4A136_group and Bacteroides were the primary taxa driving the difference between LB6 and control. There was a significant separation of cecal and serum metabolites of LB6 compared to control and HB6 rats. In the cecum, arginine biosynthesis was impaired, while vitamin B6 metabolism, lysine degradation and nicotinate and nicotinamide metabolism were impaired in serum metabolite profiles. Cecal propionate and butyrate were significantly reduced in LB6 rats irrespective of sex. Host vitamin B6 deficiency but not excess significantly alters gut microbial composition and its metabolites.

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A Method to Optimize the Electron Spectrum for Simulating Thermo-Mechanical Response to X-ray Radiation

Symmetry ◽

10.3390/sym12010059 ◽

2019 ◽

Vol 12 (1) ◽

pp. 59

Author(s):

Xianwen Ran ◽

Bo Wang ◽

Kun Zhang ◽

Wenhui Tang

Keyword(s):

Electron Spectrum ◽

Mechanical Response ◽

Least Squares Method ◽

Mechanical Deformation ◽

X Rays ◽

Linear Least Squares ◽

X Ray ◽

Relativistic Electron Beams ◽

Transport Code ◽

The Difference

The X-ray pulse originating from high altitude nuclear detonation (HAND) is mainly soft X-ray and its intensity is high enough to gasify the penetrated material and then lead to the severe thermo-mechanical deformation of unpenetrated material from the gasified blow-off effect. This effect cannot be directly reproduced in a lab for the lack of the X-ray source like HAND. At present, the low-energy relativistic electron beams resulting from an electron accelerator are usually used to approximately reproduce this effect, but the difference in the energy-deposited profile in materials between the electron and X-ray cannot be eliminated. In this paper, the symmetric linear least squares method was used to optimize the electron spectrum, and the general Monte Carlo N-Particle Transport Code calculations showed the optimized spectrum can produce the same energy-deposited profile in aluminum, copper, and tantalum with the soft X-rays like 1 keV or 3 keV spectrums. This indicates that it is possible to simulate the severe thermo-mechanical deformation resulting from HAND using the optimized electron spectrums.

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Destruction of C2H4O2 isomers in ice-phase by X-rays: Implication on the abundance of acetic acid and methyl formate in the interstellar medium

Proceedings of the International Astronomical Union ◽

10.1017/s1743921317008079 ◽

2017 ◽

Vol 13 (S332) ◽

pp. 418-424

Author(s):

Marina G. Rachid ◽

K. Faquine ◽

S. Pilling

Keyword(s):

Acetic Acid ◽

Cross Sections ◽

Methyl Formate ◽

X Rays ◽

Formation Cross Section ◽

X Ray ◽

Synchrotron Light ◽

The Difference ◽

Astrophysical Ices

AbstractC2H4O2 isomers, methyl formate (HCOOCH3), acetic acid (CH3COOH) and glycoaldehyde (HOCH2CHO), have been detected in a lot of sources in ISM. However, their abundances are very different, with methyl formate much more abundant than the other two isomers. This fact may be related to the different destruction by ionizing radiation of these molecules. The goal of this work is experimentally study the photodissociation processes of methyl formate and acetic acid ices when exposed to broadband soft X-ray from 6 up to 2000 eV. The experiments were performed coupled to the SGM beamline in the Brazilian Synchrotron Light Source (LNLS/CNPEM) at Campinas, Brazil. The simulated astrophysical ices (12K) were monitored throughout the experiment using infrared vibrational spectroscopy. The analysis of processed ices allowed the determination of the effective destruction cross sections of the parent molecules as well as the effective formation cross section of daughter molecular species. The relative abundance between acetic acid and methyl formate (NCH3COOH/NHCOOCH3) in different astronomical scenarios and their column density evolution in the presence of X-rays were calculated and our results suggests that such radiation field can be one of the factors that explain the difference in the isomers C2H4O2 abundances. We also quantified the daugther species after the establishment of a chemical equilibrium in the samples.

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Is Subacromial Balloon Spacer Appropriate for Treatment of Irreparable Rotator Cuff Tears in Elderly Patients?

Ortopedia Traumatologia Rehabilitacja ◽

10.5604/01.3001.0013.7399 ◽

2019 ◽

Vol 21 (6) ◽

pp. 417-426

Author(s):

Kamil Yamak ◽

Hüseyin Gökhan Karahan ◽

Taşkın Altay ◽

Cemil Kayalı ◽

Fırat Ozan

Keyword(s):

Rotator Cuff ◽

Rotator Cuff Tears ◽

Dash Score ◽

X Rays ◽

Preoperative Period ◽

Subacromial Space ◽

Significant Difference ◽

The Difference ◽

Quick Dash

Background. The aim of this study was to evaluate the clinical and radiographic results of surgical treatment of irreparable rotator cuff tears by subacromial balloon spacer insertion in patients over 65 years old. Material and methods. Results of patients with failed conservative treatment for irreparable rotator cuff tears and who underwent subacromial balloon spacer insertion were evaluated retrospectively. The VAS and Quick-DASH scores were used for clinical and functional assessment. Results. Eleven patients were included. Mean age of patients was 69.1 (range: 65-77) years old. Evaluation of anteroposterior shoulder x-rays revealed Hamada grade 2 and grade 1 arthropathy in 10 patients (91%) and 1 patient (9%),respectively. Mean duration of follow-up was 45.09 (±5.43,37-52) months. The difference in the subacromial space measured from standard AP shoulder x-rays in the preoperative period, in the 6th postoperative month, and at the end of follow-up was 5.44 mm (2.29), 6.51 mm (±2.23), and 5.08 mm (±2.13), respectively. Mean Quick-DASH score was 74.49(±14.36) in the preoperative period, compared to 72.19 (±14.38) at the end of follow-up. There was no statistically significant difference between preoperative period and end of follow-up scores in terms of mean Quick-DASH scores (p= 0.232). Mean VAS score was 7.09 (±0.831) in the preoperative period and 6.64 (±0.809) at the end of follow-up. No statistically significant difference was revealed in terms of mean VAS scores when preoperative and end of follow-up scores were compared (p=0.333). Conclusion. Clinical and radiographic results of subacromial balloon spacer insertion in the treatment of irreparable rotator cuff tears could not be evaluated as satisfactory.

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Metal ion – biomolecule interactions. Part 16. C(2)-H isotopic exchange in Co(III)-coordinated imidazoles

Canadian Journal of Chemistry ◽

10.1139/v95-097 ◽

1995 ◽

Vol 73 (6) ◽

pp. 772-780 ◽

Cited By ~ 8

Author(s):

Erwin Buncel ◽

Fan Yang ◽

Robert Y. Moir ◽

Ikenna Onyido

Keyword(s):

Metal Ions ◽

Metal Ion ◽

Hydrogen Exchange ◽

Isotopic Exchange ◽

Negative Charge ◽

Ligand Complex ◽

Transition State Stabilization ◽

Anionic Species ◽

Metal Ligand ◽

Ligand Bond

Transition-metal-bound imidazoles are suitable models for evaluating the roles of metal ions in biomolecules having the imidazole moiety and similar heterocyclic residues as part of their structure. Such studies provide useful insights into metal–biomolecule interactions in biological systems, especially when the lability of the metal–ligand bond is substantially reduced, such that the identity of the metal–ligand complex is preserved during the course of the reaction under investigation. The present paper reports on a kinetic study of tritium exchange from the C(2) position of the imidazole moiety in the substitution-inert complex cations [Co(NH3)5[2-3H]-imidazole]3+ (1) and [Co(NH3)5-1-methyl-[2-3H]-imidazole]3+ (2). Rate–pH profiles have been determined in aqueous solution at 60 °C. Both substrates are believed to react through rate-determining attack of hydroxide ion (kM+ pathway) at C(2)-T. Dissection of the kinetic data reveals an additional pathway for 1 consequent upon deprotonation of its pyrrole-like N-H(T) to yield 3, which is then attacked by hydroxide at C(2) (kM pathway). The ratio kM+/kM = 103 that is obtained is in accord with the expected reduced reactivity of 3. Comparison of the present data with those reported for a variety of heterocyclic substrates shows that the order of reactivity, protonated [Formula: see text] metal ion coordinated [Formula: see text] neutral form of substrates, prevails. The superiority of the proton over metal ions in catalyzing isotopic hydrogen exchange is attributed to its larger ground state acidifying effect coupled with the greater transition state stabilization it affords, relative to metal ions. The exchange reaction of 3 via the kM pathway is the first example of a reactive anionic species in which the negative charge is located α to the exchanging C-H. Keywords: tritium exchange, cobalt (III)-coordinated imidazoles.

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