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We investigated the material properties of Cremonese soundboards using a wide range of spectroscopic, microscopic, and chemical techniques. We found similar types of spruce in Cremonese soundboards as in modern instruments, but Cremonese spruces exhibit unnatural elemental compositions and oxidation patterns that suggest artificial manipulation. Combining analytical data and historical information, we may deduce the minerals being added and their potential functions—borax and metal sulfates for fungal suppression, table salt for moisture control, alum for molecular crosslinking, and potash or quicklime for alkaline treatment. The overall purpose may have been wood preservation or acoustic tuning. Hemicellulose fragmentation and altered cellulose nanostructures are observed in heavily treated Stradivari specimens, which show diminished second‐harmonic generation signals. Guarneri's practice of crosslinking wood fibers via aluminum coordination may also affect mechanical and acoustic properties. Our data suggest that old masters undertook materials engineering experiments to produce soundboards with unique properties., ICP‐MS is used to identify the unique mineral recipe used by Antonio Stradivari to treat his spruce wood, the material for the violin top plate. Chemical manipulation led to hemicellulose fragmentation and cellulose rearrangement. Incorporating engineered wood may contribute to the unique tonal qualities of these acclaimed instruments.

Following the futile efforts of generations to reach the high standard of excellence achieved by the luthiers in Cremona, Italy, by variations of design and plate tuning, current interest is being focused on differences in material properties. The long-standing question whether the wood of Stradivari and Guarneri were treated with wood preservative materials could be answered only by the examination of wood specimens from the precious antique instruments. In a recent communication (Nature, 2006), we reported about the degradation of the wood polymers in instruments of Stradivari and Guarneri, which could be explained only by chemical manipulations, possibly by preservatives. The aim of the current work was to identify the minerals from the small samples of the maple wood which were available to us from the antique instruments. The ashes of wood from one violin and one cello by Stradivari, two violins by Guarneri, one viola by H. Jay, one violin by Gand-Bernardel were analyzed and compared with a variety of commercial tone woods. The methods of analysis were the following: back-scattered electron imaging, X-ray fluorescence maps for individual elements, wave-length dispersive spectroscopy, energy dispersive X-ray spectroscopy and quantitative microprobe analysis. All four Cremonese instruments showed the unmistakable signs of chemical treatments in the form of chemicals which are not present in natural woods, such as BaSO4, CaF2, borate, and ZrSiO4. In addition to these, there were also changes in the common wood minerals. Statistical evaluation of 12 minerals by discriminant analysis revealed: a. a difference among all four Cremona instruments, b. the difference of the Cremonese instruments from the French and English antiques, and c. only the Cremonese instruments differed from all commercial woods. These findings may provide the answer why all attempts to recreate the Stradivarius from natural wood have failed. There are many obvious implications with regard to how the green tone wood should be treated, which chould lead to changes in the practice of violin-making. This research should inspire others to analyze more antique violins for their chemical contents.

Whether or not the great Italian violin-makers used wood that had been chemically processed in order to preserve it and enhance the instrument's sound quality has long been a contentious issue. Here we use nuclear magnetic resonance and infrared spectroscopy to analyse organic matter in wood taken from antique instruments made by Stradivari and Guarneri del Gesu. Our results indicate that the wood used by the masters could indeed have been chemically treated, a technique that may inspire an approach to violin making that is more chemistry-based.

Cationic amino acids, arginine and lysine partition differentially from water into aqueous micellar sodium dodecanoate. Conversely, partitioning of serine, glycine, aspartic acid, glutamic acid, threonine, alanine, proline, valine, leucine, phenylalanine and isoleucine do not vary appreciably. Partitioning from neat hexane into dodecylammonium propionate trapped water in hexane is, however, dependent upon both electrostatic and hydrophobic interactions. These results imply that the interior of dodecylammonium propionate aggregates is negatively charged and is capable of hydrogen bonding in addition to providing a hydrophobic environment. The solubilities of amino acids in neat hexane substantiate the previously derived amino acid hydrophobicity scale. Relevance of partitioning in these systems to the postulated selective amino acid compartmentalization is discussed.

Cyclic AMP was converted to its phosphotriesters according to the classical approach of phosphate activation with a sulfonyl chloride, followed by esterification with an alcohol. The methyl, ethyl, propyl, butyl and cetyl triesters were prepared, and some of their physical-chemical properties determined. Alkaline hydrolysis of these alkyl phosphotriesters resulted predominantly in ring opening. On the other hand, nucleophilic attack by thiourea led to the formation of cAMP as the main product. The conclusion can be drawn from these results that cAMP phosphotriesters could serve as suitable storage forms of cAMP, and cyclic triesters may be the best vehicle of transporting nucleotides through biological membranes.

By the sheer beauty of its vibrant sound, the voice of the violin can be intimate and enchanting like no other musical instrument. The enormous complexity of this odd resonator box has long attracted some of the best minds in science to play on it and think about how it functions. The letters of Galileo, for example, show how impatiently he awaited the completion of a violin from Cremona while he was under house arrest in 1638. Einstein was an aficionado of the violin, and a fair player throughout his life. The German chemist Richard Kuhn, winner of the Nobel Prize in 1938 for his work on carotenoids and vitamins, was an accomplished violinist. The violin also is a great cultural and scientific puzzle. It evolved from simpler, more ancient stringed instruments during the middle of the 16th century through the innovations of Italian instrument makers, such as Andrea Amati. And it was brought to ...

The partition coefficients, K-values, of adenosine, guanosine, cytidine, uridine, 51-adenylic acid (AMP), 51-guanylic acid (GMP), 51-cytidylic acid (CMP), and 51-uridylic acid (UMP) between water and aqueous sodium dodecanoate has been determined by gel filtration on Sephadex G-25. Below the critical micelle concentration of the surfactant, K-values for all nucleotides and nucleosides are similar. Differential uptake of the four nucleotides and nucleosides is observed, however, by micellar sodium dodecanoate. K-values for adenosine, AMP; guanosine, GMP; cytidine, CMP; and uridine, UMP are 6.16·103, 9.52·103; 12.0·103, 14.6·103; 19.6·103, 19.6·103, 34.2·103 and 40.3·103. Similar K-values for corresponding pairs of nucleotides and nucleosides imply that the predominant interaction is between the pyrimidine or purine rings of the substrates and the charged Stern layer of the surfactant. Prebiotic significance of these results is discussed.

The synthesis of a novel ribonucleotide analog 2'-thio-2' deoxycytidine 2':3'-O,S-phosphorothioate is described. In the first step, 2,2'-anhydro 1-beta-D-arabinosylcytosine was thiophosphorylated by the action of dithiophosphate, a process which gave predominantly the 3'-O-phosphorothioate isomer. An intramolecular displacement reaction led to the formation of the title compound. Structure and reactivity of this thioanalog differ substantially from 2':3'-CMP.

Selective compartmentalization of amino acids and nucleotides according to their polarities is proposed as a physical-chemical model for the origin of the genetic code. Assumptions made in this hypothesis are: (1) an oil-slick covered the surface of the primitive ocean, constituents of which formed association colloids or micelles at the water-oil-air interfaces; (2) depending on the polarity of the media, these aggregates possessed hydrophilic and hydrophobic interiors where selective uptake of amino acids and nucleic acid constituents could take place; and (3) condensation and polymerization in the micellar phase were enhanced. According to the chromatographically observed polarities, for example, lysine and uridylate fall into the hydrophilic compartment, and phenylalanine and adenylate are enriched in the hydrophobic environment. These components could eventually be condensed to form a charged adaptor loop with an anticodon which is complementary to the presently valid codon. Only two groups of amino acids, hydrophilic and hydrophobic, were recognized by the primitive translation mechanism. Implications of this hypothesis for the further development of the genetic code is discussed. The catalytic power of micelles have been substantiated by successful synthesis of nucleotides under relatively mild conditions using thiophosphates as high energy phosphates.

The P-O-ethyl ester of cAMP has been synthesized, its inhibition of solid and ascites tumors studied, and its pattern of urinary excretion followed. Et-cAMP is more effective than cAMP against solid sarcoma 180 in mice and against Ehrlich ascites carcinoma cells in tissue culture. The urinary excretion pattern of injected E-t-cAMP suggests that about two-thirds of the injected dose (13 mumol per animal) is retained in the rat rather than being promptly excreted. Liver slice studies of the effect on glycogenolysis suggest that the Et-cAMP is converted to cAMP intracellularly. The compound crystallizes in space group P21 with one molecule per asymmetric unit. The base ring has the anti conformation. The ethyl group is endo to the base ring and is axial in the flattened chair-conformer six-membered ring formed by the 3'-5' O-P-O cyclization. In most other respects the structure of the compound is closely similar to the known structures of other cyclic nucleotides.

Oligo 5′-thiodeoxythymidylates and oligo 5′-thiodeoxyadenylates were prepared via displacement of tosylates by thiophosphate mono- and diesters. The 5′ ends contain O-tosyl or S-phosphoryl groups, while the 3′ ends terminate in deoxythymidine. The types of starting materials used for such polymerization were 5′-O-tosyl nucleoside 3′ cyanoethyl phosphorothionates and the corresponding monoesters. Both oligonucleotide analogs possess secondary structure according to spectral evidence.

The observation that the cytidine analog, O 2 :2'-anhydro-l-β- D -arabinosylcytosine 3'-phosphate (anhydro-ara-CMP), yields 1-β- D -arabinofuranosylcytosine (ara-C) as a degradation product in vitro , prompted us to investigate the metabolism of [ 14 C]-anhydro-ara-CMP in mice. This study includes measurements of excretory rates and appearance of labeled material in the blood stream, distribution of activity in tissue at specified times, and metabolic assay of degradation products within certain mitotically active tissues. Analysis of both urine and faeces indicates that approximately 40 per cent of the labeled material remains within the animals after 24 hr. Measurement of [ 14 C] activity in the blood gave a peak absorption time at 1 hr after intraperitoneal injections. Reasonable levels of activity in the blood were present even after 72 hr. The metabolic assay of liver and spleen tissue taken at 1 hr showed anhydro-ara-C as the major metabolite, with a significant amount of ara-C and its di- and triphosphates also being formed. Cytidine phosphates were also detected. Single doses of 2000 mg/kg and daily doses of 1000 mg/kg for 5 days caused no fatalities among the test animals.

The isolation of pyrimidine oligonucleotides (isostichs) from chick erytyrocyte DNA was accomplished on a preparative scale with the goal of providing starting material for further chemical modifications. The DNA was degraded by the method of Burton and Petersen and the isostichs were obtained via paper chromatography and ion-exchange chromatography. The various isostichs were further fractionated into base compositional isomers, the frequency of which was determined as mole percent of total pyrimidines. Although this work was not intended to be an analytical study, the large quantities of DNA used allowed the measurement of most compositional isomers with an accuracy of 5% of the listed values. The data for long oligothymidylates are less reliable. The results of the present study revealed the anticipated bias in the distribution of pyrimidine isostichs in favor of longer chain lengths as compared to that expected for a random distribution. Isostichs above chain length 10 occur in amounts approximately 7 times greater than calculated.

It is proposed that inorganic thiophosphate was a versatile and highly reactive constituent of the primitive earth. Some of the ramifications of this assumption with regard to prebiotic chemistry stem from the dual nature of thiophosphate as the most superior nucleophilic agent and an energy rich phosphate. The Michael addition of thiophosphate to acrylonitrile yieldsS-cyanoethylphosphorothioate in high yield. This compound in turn can be used to phosphorylate 2′-deoxythymidine in organic solvents and in the solid state. A mixture of 5′ and 3′-dTMP were identified via chromatography, elementary analysis and NMR spectroscopy.

Oligomerization of 5′-TMP in water pools entrapped by dodecyl-ammonium chloride surfactant aggregates in benzene: hexane in the presence of dicyanodiimide at temperatures ranging from 21°–72° resulted in the formation of linear and cyclic oligonucleotides containing up to pentamers. Effects of temperature, time and surfactants have been examined. Rate constants for the formation of oligomers have been determined at five different temperatures. These data afforded values of ΔH‡ = 11.8 ± 1.9 Kcal mole−1, ΔS‡=−53α 6 e.u. and ΔG‡ = 27.4α 4.0 Kcal mole−1. Prebiotic significance of these results are discussed.

Summary We are proposing a simple model by which acidic polysaccharides of the critical charge density 1 minus/1 carbohydrate unit can be converted into anion exchangers by complexing with a trivalent cation. We have constructed a complex of alginic acid and Al3+ which was shown to bind nucleotides. It was assumed that bile acids would also be bound and, thus, Al- alginate would be hypocholesterolemic in vivo . The feeding of Al- alginate to rats which were fed a high cholesterol diet produced a marked decrease of serum cholesterol. It is proposed that Al3+ may have a nutritional role if present in conjunction with acidic polysaccharides. Ternary complexes involving lipids may exist in many biological structures.

An improvement of our strategy for the stepwise synthesis of oligo 5'-deoxy-5'-thiodeoxyribonucleotides [Chladek and Nagyvary (1972) J. Amer. Chem. Soc. 94, 2079] involves the use of 5'-O-tosylthymidine 3'-S-2-cyanoethyl phosphorothioate. The displacement of the tosylate by thymidine 3'-phosphorothioate and subsequent alkaline deblocking afforded the dinucleotide (Tps)2. The process of displacement and deblocking was repeated three more times at an average yield of 30 percent per step. The corresponding bifunctional derivative of deoxyadenosine was found much less reactive and practically unsuitable for repeated chain elongation. The ORD and CD spectra of the analogs are similar to those of the natural oligonucleotides.

The biochemical properties of several alkyl phosphotriesters of cyclic AMP were studied with respect to their interactions with beef heart protein kinase and cyclic nucleotide phosphodiesterase. Ethyl and propyl triesters did not enhance the phosphorylation of histone by protein kinase and methyl, ethyl, propyl and butyl triesters were poor competitors for the cyclic AMP binding site of the enzyme. However, these alkyl phosphotriesters were effective inhibitors of cyclic nucleotide phosphodiesterase with the K i 's arrayed in the following order: methyl > ethyl > propyl > butyl > cetyl triester. Metabolic studies with mice indicated that intraperitoneal injection of low doses of propyl triester for one week significantly increased cyclic AMP concentration.

Anhydro-araC, a precursor of araC, exhibits an unusual tissue distribution and unexpected toxicities which require an interpretation. In order to provide an explanation of these phenomena, we studied the nature of binding of anhydro-araC to some proteins and acid mucopolysaccharides in vitro using equilibrium dialysis and potentiometric titration. The results indicate significant electro-static binding of the cationic anhydro-araC to all polyanionic compounds. The physiological significance of these findings was established in mice with the help of 14 C-labeled drug. A portion of the radioactivity (15–30 per cent) could not be extracted with water but with CaCl 2 . An analysis of this fraction showed predominantly unchanged anhydro-araC and ionic metabolites. Both storage and toxicity of anhydro-araC seem to be a result of interference with the different cation exchanger biopolymers found in the mast cells and the “ground substance.”

This study was undertaken to elucidate the mechanism responsible for the hypolipidemic action of pectin. The experiments reported here were designed to test if direct molecular interactions exist between pectin and lipids. Equilibrium dialysis of pectin and taurocholate showed binding only at high nonphysiological ionic strength. When lipid microemulsions and micelles of low charge density were used, unambiguous proof of binding to pectin were obtained by NMR spectroscopy and gel exclusion chromatography. The results suggest that the interaction in mainly by hydrogen bonds involving the pectin carboxylic moieties. The quantitation of lipid binding by pectin could be established only in presence of polyvalent cations using a membrane filtration technique. Under optimum conditions, pectin can bind four times its weight in lipids. Although the techniques presented here are physical-chemical, the conclusions are highly relevant to bioavailability. These results represent the first successful demonstration of direct lipid-polysaccharide interactions in biochemistry, and they have an obvious bearing on the physiological absorption process. The intestinal binding of dietary and biliary lipids by pectin may be a major mechanism of action of this hypolipidemic polysaccharide. This paper also cells attention to techniques which could be beneficial for the in vitro evaluation of plant fibers.

Thermal activation of O 2 ,59-cyclothymidine 39-phosphate in solution and in the solid state led to the formation of thymidine oligonucleotides containing up to approximately 12 nucleotide units. Only the 39,59 internucleotide diester bonds were formed. This polymerization occurs without the addition of any activating agent or catalyst.

Several modifications of 1-β- d -arabinosylcytosine (ara-C) are described with particular regard to prolonging its presence in the tissues and lowering its toxicity. Precursors containing an isourea-ether or amidine group and a phosphate group were synthesized and studied in vitro. The most promising compound satisfying these criteria is O2:2'-anhydro-1-β- d -arabinosylcytosine 3'-phosphate (anhydro-ara-CMP). We have followed the disappearance of the anhydro-ara-C chromphore spectrophotometrically in phosphate, bicarbonate, citrate, lactate and Tris-HCl buffers of various concentration and pH. We found that the ultraviolet change was due to two concomitant firstorder reactions. The main process was a general-base catalyzed hydrolysis leading to the formation of 1-β- d -arabinosylcytosine 3'-phosphate (ara-CMP), but the formation of 2',3'-cyclic CMP was also observed to some extent. The rate constants and the arabino to ribo ratio depended on the ionic strength and the pH. In the course of studies of 14C-labeled compound in human blood in vitro, the presence of ara-C and its favorable rate of formation could be observed. It was concluded that the administration of a single dose of anhydro-ara-CMP will produce an effect similar to continuous infusion of decreasing amounts of ara-C.

IN contrast to the plausible explanations for proteinoid formation1, there seems to be no satisfactory concept for the genesis of polynucleotide templates in the presumed conditions of the primitive Earth. Only parts of the problem, such as the origin of the bases2,3 and carbohydrates4 and the synthesis of short oligonucleotides5,6, have been subjected to informative experiment. A working hypothesis of the past decade took for granted the availability of common nucleosides, but only in 1970 was a plausible, though inefficient, route to any natural nucleosides proposed7. Some recent evidence suggests, however, that natural nucleosides need not be direct precursors of the corresponding nucleotides and polynucleotides.